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Koln, Germany

The University of Cologne is the sixth oldest university in Central Europe and, with 38,000 students and 4,000 postgraduates, one of the largest universities in Germany. It is furthermore the German founding member of the Global Alliance in Management Education . Since 2012 the university was awarded in the German Universities Excellence Initiative for its overall concept. Wikipedia.


Ringe J.D.,University of Cologne
Scandinavian Journal of Clinical and Laboratory Investigation | Year: 2012

Vitamin D (cholecalciferol) is important for normal development and maintenance of the skeleton. The metabolites 25(OH)D and 1,25(OH)2D are not only important for treating rickets and osteomalacia but also for all types and clinical stages of osteoporosis. Patients with low calcium intake and a low vitamin D status are at risk to develop secondary hyperparathyroidism, increased bone resorbtion, osteopenia and fractures. This can be counteracted by a lifelong sufficient vitamin D supply plus dietary or supplementary calcium. The effects of vitamin D on muscle, balance and cognitive functions may be an added value in fracture prevention. Today it is generally accepted that a supplementation with vitamin D and calcium should be added to every specific medical treatment of osteoporosis. In contrast to this general recommendation the potency of vitamin D alone with or without calcium to reduce the incidence of falls and/or fractures is still a debated controversy. Studies and meta-analyses during the last two decades on the effect of vitamin D and calcium supplements have not resolved the controversy on the risk of falls and fractures in healthy or osteopenic elderly populations. A thorough analysis of these trials supports our clinical experience that the efficacy of vitamin D-calcium supplementation depends on factors related to patient selection, medical intervention and study design, e.g. age, mobility, preventing falls and fractures, co-morbidity, initial vitamin D status and renal function. We conclude that plain vitamin D (cholecalciferol) with sufficient calcium intake is able to reduce the risk of falls and fractures only when adopting optimal selection criteria for patients and study conditions. © 2012 Informa Healthcare.


Dietlein T.S.,University of Cologne
Ophthalmologe | Year: 2015

Background: Goniotomy has been established as the standard procedure in the treatment of congenital glaucoma for more than 50 years. Objectives: This article presents the current indications for the different antiglaucomatous procedures in children with success rates and specific complications. Methods: A selective literature search was carried out and a report of the consensus meeting 2013 concerning congenital glaucoma and personal experiences are presented. Results: Primary surgical treatment for primary congenital glaucoma mainly consists of trabeculotomy and its modifications but also of goniotomy. A widespread and increasing use of drainage device surgery can be seen in complicated types of pediatric glaucoma, such as secondary glaucoma due to aphakia, uveitis or Sturge-Weber-Krabbe syndrome. Conclusion: The visual prognosis following glaucoma surgery generally depends on successful control of the intraocular pressure as well as on amblyopia treatment. © 2015, Springer-Verlag Berlin Heidelberg.


Wieland U.,University of Cologne | Kreuter A.,Ruhr University Bochum
Current Opinion in Oncology | Year: 2011

Purpose of Review: Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), an aggressive nonmelanoma skin tumour. MCC incidence has been rising in the last decades. Immunocompromised individuals such as HIV-infected patients have an increased risk for MCC development. Recent Findings: MCPyV is found-mostly integrated into the host genome-in approximately 80% of MCC. The causal role of MCPyV in MCC development has been corroborated by several recent studies. Cutaneous MCPyV infection is acquired early in life and is widespread in the general population. In HIV-positive patients, MCPyV-DNA has been detected on the skin, on oral and anogenital mucosa, and in plucked eyebrow-hairs. Compared with healthy controls, MCPyV prevalence is increased in HIV-infected individuals and severe HIV-related immunosuppression is associated with elevated cutaneous MCPyV-DNA loads. This could explain the increased MCC risk found in HIV-infected individuals. MCC in HIV-infected patients occurs at a relatively young age and frequently on sites not exposed to sunlight. Summary: Guidelines for screening and early detection of MCC should be developed for HIV-positive patients. Future studies should evaluate changes in MCC incidence rates in HIV-infected individuals and analyse the effect of immune restoration by (early) antiretroviral therapy on MCC incidence and on cutaneous MCPyV load. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Kromer S.,University of Cologne
ESAIM - Control, Optimisation and Calculus of Variations | Year: 2012

We study integral functionals constrained to divergence-free vector fields in L p on a thin domain, under standard p-growth and coercivity assumptions, 1 < p < We prove that as the thickness of the domain goes to zero, the Gamma-limit with respect to weak convergence in L p is always given by the associated functional with convexified energy density wherever it is finite. Remarkably, this happens despite the fact that relaxation of nonconvex functionals subject to the limiting constraint can give rise to a nonlocal functional as illustrated in an example. © 2010 EDP Sciences, SMAI.


The sites of mucin-type O-glycosylation are difficult to predict, making structural analysis by mass spectrometry indispensible. This chapter refers to state-of-the-art techniques in the site localization of O-linked glycans and their structural characterization in situ using tandem ESI and MALDI mass spectrometry. Detailed protocols are provided that describe the application of nano-LC-ESI-MS/MS with alternative fragmentation modes (collision-induced dissociation vs. electron-transfer dissociation) for the analysis of O-glycopeptides. Moreover, a top-down sequencing approach by MALDI-MS is presented that is based on the in-source decay of intact glycoproteins or large glycopeptides and allows a ladder sequencing of up to 70 amino acid residues from both termini with unequivocal assignment of modified sites. © 2012 Springer Science+Business Media, LLC.


Kus D.,University of Cologne
Journal of Combinatorial Theory. Series A | Year: 2013

On the polytope defined by Feigin, Fourier and Littelmann, associated to any highest weight corresponding to a rectangular partition, we define a crystal structure of type A n. We show that this crystal is isomorphic to the one obtained from Kashiwara's crystal bases theory. Further we define on this polytope a bijective map and show that this map satisfies the properties of a weak promotion operator. This implies in particular that we provide an explicit realization of Kirillov-Reshetikhin crystals for the affine type An(1) via polytopes. © 2013 Elsevier Inc.


Foeldvari I.,Hamburger Zentrum fur Kinder und Jugendrheumatologie | Becker I.,University of Cologne
Arthritis Care and Research | Year: 2015

Objective Uveitis is a major extraarticular quality of life-restricting manifestation of juvenile idiopathic arthritis (JIA). The aim of the study is to describe the occurrence of uveitis in JIA patients receiving tumor necrosis factor inhibitors or methotrexate (MTX). Methods Patients' characteristics, treatment, and the reported first occurrence of uveitis as an adverse event were searched in the Biologics in Pediatric Rheumatology Registry. The rates per exposed patients, exposure time, and time until event were calculated. Results Uveitis was reported as an adverse event in 75 of 3,467 patients; 51 of 2,844 patients were receiving MTX, 37 of 1,700 patients were receiving etanercept, and 13 of 364 patients were receiving adalimumab. Patients with uveitis were younger (mean ± SD age 4.6 ± 4.2 versus 7.4 ± 4.5 years; P < 0.0001), more likely to be antinuclear antibody positive (69% versus 43%; odds ratio [OR] 2.7, P < 0.0001), and had extended oligoarticular JIA (OR 2.2, P = 0.0005). Patients with a uveitis diagnosis before starting treatment more often had a uveitis event (n = 28, 8.4%; OR 8.5, P < 0.0001), and more often received adalimumab (OR 2.15 [95% confidence interval 1.58-2.94], P < 0.0001). In 16 patients, a new uveitis event occurred: 11 while taking MTX (3.2 per 1,000 patient-years), 2 while taking etanercept monotherapy (1.9 per 1,000 patient-years), and 3 while taking etanercept and MTX combination (0.9 per 1,000 patient-years). A new uveitis event occurred early in the disease course after a median disease duration of 1.5 years (interquartile range [IQR] 1.3-3.8) while taking etanercept and 1.8 years (IQR 1.8-2.1) for the MTX cohort. A recurrent uveitis event was reported after a disease duration of 7.6 years (IQR 4.3-10.0) in the etanercept cohort and 4.8 years (IQR 1.0-5.8) in the MTX cohort. Univariate analysis showed that MTX, but not etanercept or adalimumab, led to a lower rate of uveitis. Conclusion Patients with a history of uveitis had higher risks for uveitis events while taking both etanercept and adalimumab. Methotrexate turned out to be protective. Few patients developed a first uveitis event while taking etanercept, while the rate is comparable to that with MTX. Uveitis may not be attributed to be an adverse drug reaction to etanercept. © 2015, American College of Rheumatology.


Schieck H.P.G.,University of Cologne
Few-Body Systems | Year: 2013

A few new considerations with respect to energy production by low-energy nuclear fusion reactions will be discussed. A summary of the present status of nuclear fusion is given with emphasis on utilizing spin-polarized particles as fuel. The reactions considered are those concerning the four- and five-nucleon systems and especially the D + D reactions for which the status of the theory and the experimental data are presented. Recent progress has been achieved by microscopic calculations of the D + D reactions. New aspects concern the increased cross sections at very low energies by electron screening as well as the dynamics of the implosion scenario in inertial-fusion pellets with polarized fuel. The need to get more experimental data is pointed out. © 2012 Springer-Verlag.


Lynch J.A.,University of Cologne | El-Sherif E.,Kansas State University | Brown S.J.,Kansas State University
Wiley Interdisciplinary Reviews: Developmental Biology | Year: 2012

Studying the embryogenesis of diverse insect species is crucial to understanding insect evolution. Here, we review current advances in understanding the development of two emerging model organisms: the wasp Nasonia vitripennis and the beetle Tribolium castaneum in comparison with the well-studied fruit fly Drosophila melanogaster. Although Nasonia represents the most basally branching order of holometabolous insects, it employs a derived long germband mode of embryogenesis, more like that of Drosophila, whereas Tribolium undergoes an intermediate germband mode of embryogenesis, which is more similar to the ancestral mechanism. Comparing the embryonic development and genetic regulation of early patterning events in these three insects has given invaluable insights into insect evolution. The similar mode of embryogenesis of Drosophila and Nasonia is reflected in their reliance on maternal morphogenetic gradients. However, they employ different genes as maternal factors, reflecting the evolutionary distance separating them. Tribolium, on the other hand, relies heavily on self-regulatory mechanisms other than maternal cues, reflecting its sequential nature of segmentation and the need for reiterated patterning. © 2011 Wiley Periodicals, Inc.


Erdmann E.,University of Cologne
Indian Heart Journal | Year: 2010

Beta-blockers (BB) substantially improve survival in chronic heart failure and after myocardial infarction. However, concern about side-effects may deter clinicians from prescribing these life-saving drugs. In reality, absolute contraindications are rare. Only 3-5% of patients are intolerant because of hypotension or bradycardia. Data from randomized controlled trials and retrospective studies show that most patients eligible to receive BB tolerate them well. BB are not contraindicated in chronic obstructive pulmonary disease (COPD); in fact, these patients also benefit because of their high cardiovascular risk. In patients with COPD, as in the elderly, BB should be started at a low dose and uptitrated slowly. Monitoring of lung Junction during initiation is important, as undiagnosed coexistent asthma could be revealed. When patients are unaware of the drug in use, erectile dysfunction (ED) is reported no more often with BB than with any other drug prescribed for heart failure or hypertension. However, when patients are aware of the potential side-effects of BB, the resultant anxiety may cause ED. Patients should be reassured that BB prolong life and in the great majority are not the cause of ED, which may rather be related to the underlying disease (diabetes, hypertension, and atherosclerosis).


Lechartier B.,Ecole Polytechnique Federale de Lausanne | Rybniker J.,Ecole Polytechnique Federale de Lausanne | Rybniker J.,University of Cologne | Zumla A.,University College London | Cole S.T.,Ecole Polytechnique Federale de Lausanne
EMBO Molecular Medicine | Year: 2014

The expectation that genomics would result in new therapeutic interventions for infectious diseases remains unfulfilled. In the post-genomic era, the decade immediately following the availability of the genome sequence of Mycobacterium tuberculosis, tuberculosis (TB) drug discovery relied heavily on the target-based approach but this proved unsuccessful leading to a return to whole cell screening. Genomics underpinned screening by providing knowledge and many enabling technologies, most importantly whole genome resequencing to find resistance mutations and targets, and this resulted in a selection of leads and new TB drug candidates that are reviewed here. Unexpectedly, many new targets were found to be 'promiscuous' as they were inhibited by a variety of different compounds. In the post-post-genomics era, more advanced technologies have been implemented and these include high-content screening, screening for inhibitors of latency, the use of conditional knock-down mutants for validated targets and siRNA screens. In addition, immunomodulation and pharmacological manipulation of host functions are being explored in an attempt to widen our therapeutic options. © 2014 The Authors.


Calderwood A.,John Innes Center | Kopriva S.,John Innes Center | Kopriva S.,University of Cologne
Nitric Oxide - Biology and Chemistry | Year: 2014

Sulfur is essential in all organisms for the synthesis of amino acids cysteine and methionine and as an active component of numerous co-factors and prosthetic groups. However, only plants, algae, fungi, and some prokaryotes are capable of using the abundant inorganic source of sulfur, sulfate. Plants take sulfate up, reduce it, and assimilate into organic compounds with cysteine being the first product of the pathway and a donor of reduced sulfur for synthesis of other S-containing compounds. Cysteine is formed in a reaction between sulfide, derived from reduction of sulfite and an activated amino acid acceptor, O-acetylserine. Sulfide is thus an important intermediate in sulfur metabolism, but numerous other functions in plants has been revealed. Hydrogen sulfide can serve as an alternative source of sulfur for plants, which may be significant in anaerobic conditions of waterlogged soils. On the other hand, emissions of hydrogen sulfide have been detected from many plant species. Since the amount of H2S discharged correlated with sulfate supply to the plants, the emissions were considered a mechanism for dissipation of excess sulfur. Significant hydrogen sulfide emissions were also observed in plants infected with pathogens, particularly with fungi. H2S thus seems to be part of the widely discussed sulfur- induced-resistance/sulfur-enhanced-defense. Recently, however, more evidence has emerged for a role for H2S in regulation and signaling. Sulfide stabilizes the cysteine synthase complex, increasing so the synthesis of its acceptor O-acetylserine. H2S has been implicating in regulation of plant stress response, particularly draught stress. There are more and more examples of processes regulated by H 2S in plants being discovered, and hydrogen sulfide is emerging as an important signaling molecule, similar to its role in the animal and human world. How similar the functions, and homeostasis of H2S are in these diverse organisms, however, remains to be elucidated. © 2014 Elsevier Inc. All rights reserved.


Mittelstaedt P.,University of Cologne
Foundations of Physics | Year: 2011

Since the advent of Modern Physics in 1905, we observe an increasing activity of "interpreting" the new theories. We mention here the theories of Special Relativity, General Relativity and Quantum Mechanics. However, similar activities for the theories of Classical Physics were not known. We ask for the reasons for the different ways to treat classical physics and modern physics. The answer, that we provide here is very surprising: the different treatments are based on a fundamental misunderstanding of the theories of classical physics. © 2011 Springer Science+Business Media, LLC.


Kuerten S.,University of Cologne | Lehmann P.V.,Case Western Reserve University | Lehmann P.V.,Cellular Technology Ltd
Journal of Interferon and Cytokine Research | Year: 2011

Experimental autoimmune encephalomyelits (EAE) has been widely studied as a model for multiple sclerosis (MS). EAE also holds a special place in basic autoimmune research. It is induced by immunizing healthy, naïve mice with neuroantigen. Unlike in spontaneous autoimmune models, one can therefore clearly define the initiation time point, the inducing antigen, the circumstances of the immunization that elicit a pathogenic-or nonpathogenic-T cell response, and many other parameters that are required for the induction and perpetuation of autoimmune central nervous system pathology. In the following, we will provide an overview of our current understanding of the discrete steps that lead to the pathogenesis of EAE, and we will highlight several junctions at which the perpetuation or abortive course of the disease is defined. It has become abundantly clear that the induction of a pathogenic CD4 + T cell response is a necessary requirement for the induction of EAE. However, many downstream mechanisms need to be considered if we want to understand the pathomechanisms that define the variable outcomes of EAE, and by inference, of MS. © 2011, Mary Ann Liebert, Inc.


Nimtz G.,University of Cologne
Foundations of Physics | Year: 2011

Experiments with evanescent modes and tunneling particles have shown that (i) their signal velocity may be faster than light, (ii) they are described by virtual particles, (iii) they are nonlocal and act at a distance, (iv) experimental tunneling data of phonons, photons, and electrons display a universal scattering time at the tunneling barrier front, and (v) the properties of evanescent, i. e. tunneling modes are not compatible with the special theory of relativity. © 2011 Springer Science+Business Media, LLC.


Unverzagt S.,Martin Luther University of Halle Wittenberg | Prondzinsky R.,Martin Luther University of Halle Wittenberg | Peinemann F.,University of Cologne
Journal of Clinical Epidemiology | Year: 2013

Objectives: To assess whether the reported trial characteristics are associated with treatment effects on all-cause mortality within critical care medicine. Study Design and Setting: We identified all eligible randomized controlled trials (RCTs) from Cochrane Reviews on patients with sepsis, septic shock, and cardiogenic shock. Risk of bias was judged on 12 trial characteristics, including the differentiation between single-center and multicenter trials. Hierarchical random-effects models quantified the impact of the risk of bias items on the reported effect estimates of mortality. Results: Twelve meta-analyses that involved 82 RCTs were selected and judged. Single-center trials estimated a significant larger treatment effect compared with multicenter trials (ratio of odds ratios, 0.64; 95% confidence interval: 0.47, 0.87). Treatment effect tended to be overestimated with selective reporting of preplanned end points. Biases in different trial characteristics are unlikely to operate independently and may have modified these associations. Conclusion: The results of this study highlight a substantial difference in treatment effect estimates between single-center and multicenter trials. Therefore, we recommend that results from single-center trials should be cautiously used for decision making. © 2013 Elsevier Inc. All rights reserved.


Tokano T.,University of Cologne
Aeolian Research | Year: 2010

Numerous linear dunes with eastward streamline pattern on Titan have mostly been interpreted as evidence of predominantly westerly (eastward) equatorial surface winds, although such winds are meteorologically hard to understand. Simulation with a general circulation model shows that the observed dune alignment nearly parallel to the equator maximizes the gross bedform-normal transport for seasonally reversing wind. Many dunes are found to be oblique or transverse to the resultant drift direction. The eastward streamline pattern of Titan's dunes may be a result of occasional fast westerlies that elongate the dunes eastward. These winds are turbulent, and are predicted to occur during the equinoctial passage of the intertropical convergence zone. A large threshold speed for sand transport can preclude westward sand transport although the average equatorial surface wind is easterly. Global-scale topography is found to have little impact on the dune orientation. © 2010 Elsevier B.V.


Bohaty Koln J.,University of Cologne
Neues Jahrbuch fur Geologie und Palaontologie - Abhandlungen | Year: 2010

The classic Lower Givetian crinoid occurrence of the northeastern slope of the railway cut near the station of Gerolstein (northwestern Rhineland-Palatinate, westernmost Germany) is famous for yielding an outstanding diversity of the monobathrid camerate family Hexacrinitidae. Following a short palaeogeographical and stratigraphical introduction of the Gerolstein Syncline (Eifel, Rhenish Massif), the previously described "Hexacrinites" species of this locality are revised. They clearly differ from the type species Platycrinus interscapularis (genus Hexacrinites) by the development of uniserial arms, longer aboral cups and other morphological criteria, like a single posterior interradial plate. Therefore, most of the Eifel species are assigned to the genus Megaradialocrinus (with Megaradialocrinus conicus as its type species), which is herein transferred to superfamily Hexacrinitoidea and family Hexacrinitidae. The extent of morphological differences among other hexacrinitids is discussed and may define further intergeneric differentiation. Five new species are described: Megaradialocrinus aliculatus n. sp., (?)M bulbiformis n. sp., M. piriculaformis n. sp., M. theissi n. sp. and M. winteri n. sp. The homonym "Hexacrinites magnificus" sensu Hauser (2007a) is renamed: Megaradialocrinus globohirsutus nomen novum. © 2010 Schweizerbart'sche Verlagsbuchhandlung, Stuttgart, Germany.


Gaertner J.,University of Cologne
Current pain and headache reports | Year: 2013

Decades after the publication of the World Health Organization's analgesic ladder, cancer pain is still a major cause of suffering for patients with cancer and affects millions of people worldwide. Owing to the increasing incidence of cancer, cancer-related pain is a major public health problem worldwide. Unfortunately, current research revealed that available options for the successful treatment of cancer pain is still massively underutilized by physicians, and many patients suffer from insufficiently controlled pain despite available treatment options. This review aims to present a concise update about new data or treatment recommendations from the field of cancer pain management. Therefore, information from guidelines, systematic reviews, and original articles that were published in the year 2012 are presented. Specifically, the publication covers information on tapentadol, fixed oxycodone/naloxone combinations, rapid onset fentanyl, nabiximols, ketamine, denusomab, and specialized psychosocial interventions including early palliative care.


Eisenhauer N.,University of Minnesota | Cesarz S.,University of Gottingen | Koller R.,University of Cologne | Worm K.,University of Minnesota | Reich P.B.,University of Minnesota
Global Change Biology | Year: 2012

The world's ecosystems are subjected to various anthropogenic global change agents, such as enrichment of atmospheric CO 2 concentrations, nitrogen (N) deposition, and changes in precipitation regimes. Despite the increasing appreciation that the consequences of impending global change can be better understood if varying agents are studied in concert, there is a paucity of multi-factor long-term studies, particularly on belowground processes. Herein, we address this gap by examining the responses of soil food webs and biodiversity to enrichment of CO 2, elevated N, and summer drought in a long-term grassland study at Cedar Creek, Minnesota, USA (BioCON experiment). We use structural equation modeling (SEM), various abiotic and biotic explanatory variables, and data on soil microorganisms, protozoa, nematodes, and soil microarthropods to identify the impacts of multiple global change effects on drivers belowground. We found that long-term (13-year) changes in CO 2 and N availability resulted in modest alterations of soil biotic food webs and biodiversity via several mechanisms, encompassing soil water availability, plant productivity, and - most importantly - changes in rhizodeposition. Four years of manipulation of summer drought exerted surprisingly minor effects, only detrimentally affecting belowground herbivores and ciliate protists at elevated N. Elevated CO 2 increased microbial biomass and the density of ciliates, microarthropod detritivores, and gamasid mites, most likely by fueling soil food webs with labile C. Moreover, beneficial bottom-up effects of elevated CO 2 compensated for detrimental elevated N effects on soil microarthropod taxa richness. In contrast, nematode taxa richness was lowest at elevated CO 2 and elevated N. Thus, enrichment of atmospheric CO 2 concentrations and N deposition may result in taxonomically and functionally altered, potentially simplified, soil communities. Detrimental effects of N deposition on soil biodiversity underscore recent reports on plant community simplification. This is of particular concern, as soils house a considerable fraction of global biodiversity and ecosystem functions. © 2011 Blackwell Publishing Ltd.


Topolinski S.,University of Cologne
Cognition and Emotion | Year: 2014

Earlier theories on humour assume that funniness stems from the incongruity resolution of the surprising punchline and thus an insight into the joke's meaning. Applying recent psychological theorising that insight itself draws on processing fluency being the ease and speed with which mental content is processed, it is predicted that increasing the fluency of processing the punchline of a joke increases funniness. In Experiments 1 and 2, significant nouns from the punchlines or from the beginnings of jokes were presented before a joke was rated in funniness. Pre-exposing punchline words 15 minutes and even only 1 minute before the eventual joke led to increased funniness ratings. In contrast, pre-exposing punchline words directly before a joke led to decreased funniness ratings. Furthermore, pre-exposing the beginning of a joke 1 minute before the joke had no effects on funniness. Experiment 3 ruled out exposure-facilitated punchline anticipation as alternative mechanism, and Experiment 4 replicated this fluency effect with typing font as manipulation. These findings also show that pre-exposing a punchline, which in common knowledge should spoil a joke, can actually increase funniness under certain conditions. © 2013 Taylor & Francis.


Bourouaine S.,Max Planck Institute for Solar System Research | Marsch E.,Max Planck Institute for Solar System Research | Neubauer F.M.,University of Cologne
Geophysical Research Letters | Year: 2010

Correlations are studied between the power density of transverse waves having frequencies between 0.01 and 1 normalized to the proton gyrofrequency in the plasma frame and the ratio of the perpendicular and parallel temperature of the protons. The wave power spectrum is evaluated from high-resolution 3D magnetic field vector components, and the ion temperatures are derived from the velocity distribution functions as measured in fast solar wind during the Helios-2 primary mission at radial distances from the Sun between 0.3 AU and 0.9 AU. From our statistical analysis, we obtain a striking correlation between the increases in the proton temperature ratio and enhancements in the wave power spectrum. Near the Sun the transverse part of the wave power is often found to be by more than an order of magnitude higher than its longitudinal counterpart. Also the measured ion temperature anisotropy appears to be limited by the theoretical threshold value for the ion-cyclotron instability. This suggests that high-frequency Alfvn-cyclotron waves regulate the proton temperature anisotropy. Copyright 2010 by the American Geophysical Union.


In order to fulfil the EU-limitations of fine dust and traffic-produced gases Cologne installed 2008 one of the first German environmental zones, from which stepwise vehicles with too high emissions will be locked out. Verification of effectiveness and the research on further strategies to reduce fine dust are studied as promising applications of a method on discrimination of aerosol components from different origins (Weckwerth, 2001). New measurements in Cologne gave several implications on supports, especially in connection with traffic abrasion from brakes, tires and rails. © 2010.


Hallek M.,University of Cologne
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2013

The management of chronic lymphocytic leukemia (CLL) is undergoing profound changes. Several new drugs have been approved for CLL treatment (fludarabine, bendamustine, and the monoclonal antibodies alemtuzumab, rituximab, and ofatumumab) and many more drugs are in advanced clinical development to be approved for this disease. In addition, the extreme heterogeneity of the clinical course and our improved ability to foresee the prognosis of this leukemia by the use of clinical, biological, and genetic parameters now allow us to characterize patients with a very mild onset and course, an intermediate prognosis, or a very aggressive course with high-risk leukemia. Therefore, it becomes increasingly challenging to select the right treatment strategy for each condition. This article summarizes the currently available diagnostic and therapeutic tools and gives an integrated recommendation of how to manage CLL in 2013. Moreover, I propose a strategy how we might integrate the novel agents for CLL therapy into sequential treatment approaches in the near future.


Strelkowa N.,Imperial College London | Lassig M.,University of Cologne
Genetics | Year: 2012

The seasonal influenza A virus undergoes rapid evolution to escape human immune response. Adaptive changes occur primarily in antigenic epitopes, the antibody-binding domains of the viral hemagglutinin. This process involves recurrent selective sweeps, in which clusters of simultaneous nucleotide fixations in the hemagglutinin coding sequence are observed about every 4 years. Here, we show that influenza A (H3N2) evolves by strong clonal interference. This mode of evolution is a red queen race between viral strains with different beneficial mutations. Clonal interference explains and quantifies the observed sweep pattern: we find an average of at least one strongly beneficial amino acid substitution per year, and a given selective sweep has three to four driving mutations on average. The inference of selection and clonal interference is based on frequency time series of single-nucleotide polymorphisms, which are obtained from a sample of influenza genome sequences over 39 years. Our results imply that mode and speed of influenza evolution are governed not only by positive selection within, but also by background selection outside antigenic epitopes: immune adaptation and conservation of other viral functions interfere with each other. Hence, adapting viral proteins are predicted to be particularly brittle. We conclude that a quantitative understanding of influenza's evolutionary and epidemiological dynamics must be based on all genomic domains and functions coupled by clonal interference. © 2012 by the Genetics Society of America.


Resource quality for aquatic consumers is often determined by the content of essential polyunsaturated fatty acids (PUFA) in the diet. Seasonal field sampling and controlled laboratory experiments with the invasive Ponto-Caspian mysid Limnomysis benedeni revealed high amounts of PUFA, in particular eicosanoids that are important for fish nutrition. This suggests a potential trophic upgrading in the aquatic food web through the invasive mysid. © 2013 The Author.


Wopfner H.,University of Cologne
Geological Society Special Publication | Year: 2013

In the period between the Westphalian and the Early Triassic, climatic conditions across Gondwana changed from the Gondwana-wide glaciation in the Late Carboniferous-Early Permian to warm to hot, semi-humid to arid conditions by the Late Permian-Early Triassic. In Afro-Arabia, glaciers advanced to 40° palaeolatitude creating a steep gradient between them and the temperatehumid environment in the vicinity of the equator. Synchronous deglaciation associated with a eustatic rise of sea level in the Early Sakmarian was followed by a flattening of the climate gradient and increased humidity, expressed by blackwater rivers and coal swamps between the South Pole and about 508 palaeolatitude and increasing aridity towards the equator. Brief poleward advances of hot aridity are evident around the Kungurian. Expansion of the hot climate zone to the south took place in the Middle Permian, commencing with a humid to semi-humid phase in the south and semi-arid to arid conditions towards the north. A short pluvial event is locally indicated at the beginning of the Triassic, but warm semi-arid to semi-humid conditions prevailed in the south and hot aridity near the equator. There are variations of that general theme in eastern Gondwana, but the fundamental changes in climate-controlled depositional environments occurred almost synchronously over the whole of Gondwana, including Antarctica. The slight drift of Gondwana towards the equator is therefore an unlikely cause for these changes, as are modifications of ocean-continent geometries or of atmospheric composition. As the main driver was temperature it is suggested that governing control, not only of global temperature but also of the intensity of geotectonic activities, was imposed on the solar system by forces emanating from our galaxy (cosmic ray flux, magnetic intensity, gravitational vectors) and their variation over the course of a galactic year (the time for the solar system to orbit the core of the galaxy). © The Geological Society of London 2013.


Howley P.M.,Harvard University | Pfister H.J.,University of Cologne
Virology | Year: 2015

A role for the beta genus HPVs in keratinocyte carcinoma (KC) remains to be established. In this article we examine the potential role of the beta HPVs in cancer revealed by the epidemiology associating these viruses with KC and supported by oncogenic properties of the beta HPV proteins. Unlike the cancer associated alpha genus HPVs, in which transcriptionally active viral genomes are invariably found associated with the cancers, that is not the case for the beta genus HPVs and keratinocyte carcinomas. Thus a role for the beta HPVs in KC would necessarily be in the carcinogenesis initiation and not in the maintenance of the tumor. © 2015 Elsevier Inc.


Brunkwall J.,University of Cologne | Lammer J.,University of Vienna | Taylor P.,St. Guys and Thomas Hospitals
European Journal of Vascular and Endovascular Surgery | Year: 2012

Acute dissection of the descending thoracic aorta carries a 30-day mortality of around 10% with best medical treatment (BMT). In addition, about 25% will develop an aneurysm during the following 4-5 years. This is the first ever randomised trial on acute dissections comparing BMT with BMT and stent grafting of the proximal tear in patients having an uncomplicated acute dissection of the descending aorta. The commonly used temporal definition of acute dissection being within 14 days of onset of symptoms is applied. A total of 61 patients will be randomised and followed at regular intervals (1, 3, 6, 12, 18, 24, 30 and 36 months) after acute dissection. Thrombosis of the false lumen, aortic enlargement and rupture are the primary end points. The study will examine whether aortic remodelling occurs after stent grafting in acute type B dissections, and its effect on aneurysm formation, rupture and re-intervention. © 2012 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.


Objectives:The present study aimed to analyse the clinical and neuroimaging features of a consecutive series of adult patients with spinal cord injury without radiographic abnormality (SCIWORA) receiving early magnetic resonance imaging (MRI), and to apply the recently proposed MRI classification system.Methods:Grade of neurologic impairment at admission and discharge was reported according to the American Spinal Injury Association Impairment Scale (AIS). A detailed analysis and categorisation of the extra- and intramedullary MRI findings was performed, and the relationship between imaging type and neurological outcome was described.Results:Twenty-six adult patients (17 male and 9 female) with SCIWORA were identified (mean age of 52 years). The distribution of the initial AIS grade was 8% A (n=2), 19% B (n=5), 31% C (n=8) and 42% D (n=11) at admission and 15% (n=4) C, 58% (n=15) D and 27% (n=7) E at discharge, respectively. Type I SCIWORA was found in 23% (n=6) and type II in 77% (n=20) (IIa: 0%, IIb: 25%, IIc: 75%). The mean improvement of AIS grade in patients with type I lesions was 1.5 (median 1, range 1–3) and 0.9 (median 1, range 0–3) in type II.Conclusion:The findings underline the prognostic role of early MRI for adult patients with SCIWORA and support the use of the recently introduced MRI classification system.Level of evidence:Prognostic study, level III.Spinal Cord advance online publication, 16 February 2016; doi:10.1038/sc.2016.13. © 2016 International Spinal Cord Society


Frick R.A.,University of Cologne
European Physical Journal C | Year: 2014

We consider a free particle in a de Sitter spacetime. We use a picture in which the analogs of the Schrödinger operators of the particle are independent of both the time and the space coordinates. These operators induce operators which are related to Killing vectors of the de Sitter spacetime. © 2014, The Author(s).


Ali Saberi A.,University of Tehran | Ali Saberi A.,University of Cologne
Physical Review Letters | Year: 2013

Remarkable global correlations exist between geometrical features of terrestrial surfaces on Earth, current mean sea level, and its geological internal processes whose origins have remained an essential goal in the earth sciences. Theoretical modeling of the ubiquitous self-similar fractal patterns observed on Earth and their underlying rules is indeed of great importance. Here I present a percolation description of the global topography of Earth in which the present mean sea level is automatically singled out as a critical level in the model. This finding elucidates the origins of the appearance of scale invariant patterns on Earth. The criticality is shown to be accompanied by a continental aggregation, unraveling an important correlation between the water and long-range topographic evolutions. To have a comparison point in hand, I apply such an analysis to the lunar topography which reveals various characteristic features of the Moon. © 2013 American Physical Society.


Altland A.,University of Cologne | Egger R.,Heinrich Heine University Dusseldorf
Physical Review Letters | Year: 2013

We study multiple helical nanowires in proximity to a common mesoscopic superconducting island, where Majorana fermion bound states are formed. We show that a weak finite charging energy of the center island may dramatically affect the low-energy behavior of the system. While for strong charging interactions, the junction decouples the connecting wires, interactions lower than a nonuniversal threshold may trigger the flow towards an exotic Kondo fixed point. In either case, the ideally Andreev reflecting fixed point characteristic for infinite capacitance (grounded) devices gets destabilized by interactions. © 2013 American Physical Society.


Cornely O.A.,University of Cologne | Crook D.W.,Microbiology and Infectious Diseases | Esposito R.,Clinica delle Malattie Infettive e Tropicali | Poirier A.,Center Hospitalier Regional Of Trois Rivieres | And 5 more authors.
The Lancet Infectious Diseases | Year: 2012

Background: Infection with Clostridium difficile is the primary infective cause of antibiotic-associated diarrhoea. We aimed to compare efficacy and safety of fidaxomicin and vancomycin to treat patients with C difficile infection in Europe, Canada, and the USA. Methods: In this multicentre, double-blind, randomised, non-inferiority trial, we enrolled patients from 45 sites in Europe and 41 sites in the USA and Canada between April 19, 2007, and Dec 11, 2009. Eligible patients were aged 16 years or older with acute, toxin-positive C difficile infection. Patients were randomly allocated (1:1) to receive oral fidaxomicin (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was clinical cure, defined as resolution of diarrhoea and no further need for treatment. An interactive voice-response system and computer-generated randomisation schedule gave a randomisation number and medication kit number for each patient. Participants and investigators were masked to treatment allocation. Non-inferiority was prespecified with a margin of 10%. Modified intention-to-treat and per-protocol populations were analysed. This study is registered with ClinicalTrials.gov, number NCT00468728. Findings: Of 535 patients enrolled, 270 were assigned fidaxomicin and 265 vancomycin. After 26 patients were excluded, 509 were included in the modified intention-to-treat (mITT) population. 198 (91·7%) of 216 patients in the per-protocol population given fidaxomicin achieved clinical cure, compared with 213 (90·6%) of 235 given vancomycin, meeting the criterion for non-inferiority (one-sided 97·5% CI -4·3%). Non-inferiority was also shown for clinical cure in the mITT population, with 221 (87·7%) of 252 patients given fidaxomicin and 223 (86·8%) of 257 given vancomycin cured (one-sided 97·5% CI -4·9%). In most subgroup analyses of the primary endpoint in the mITT population, outcomes in the two treatment groups did not differ significantly; although patients receiving concomitant antibiotics for other infections had a higher cure rate with fidaxomicin (46 [90·2%] of 51) than with vancomycin (33 [73·3%] of 45; p=0·031). Occurrence of treatment-emergent adverse events did not differ between groups. 20 (7·6%) of 264 patients given at least one dose of fidaxomicin and 17 (6·5%) of 260 given vancomycin died. Interpretation: Fidaxomicin could be an alternative treatment for infection with C difficile, with similar efficacy and safety to vancomycin. Funding: Optimer Pharmaceuticals. © 2012 Elsevier Ltd.


Fabri M.,University of California at Los Angeles | Fabri M.,University of Cologne | Realegeno S.E.,University of California at Los Angeles | Jo E.-K.,Chungnam National University | Modlin R.L.,University of California at Los Angeles
Current Opinion in Immunology | Year: 2011

There is compelling evidence demonstrating a key role for autophagy in host defense against microbial infections. Induction and regulation of autophagy involves complex pathways including signaling molecules that have widespread roles in cell biological functions. For example, inhibiting mTOR by rapamycin, the most widely used chemical approach to induce autophagy, can also result in immunosupression. Nevertheless, advances in our understanding of autophagy provide a new opportunity to modulate host cellular responses as a potential therapeutic strategy to combat microbial infections in humans. © 2010 Elsevier Ltd.


Hofmann W.,University of Cologne | Wisneski D.C.,University of Illinois at Chicago | Brandt M.J.,University of Tilburg | Skitka L.J.,University of Illinois at Chicago
Science | Year: 2014

The science of morality has drawn heavily on well-controlled but artificial laboratory settings. To study everyday morality, we repeatedly assessed moral or immoral acts and experiences in a large (N = 1252) sample using ecological momentary assessment. Moral experiences were surprisingly frequent and manifold. Liberals and conservatives emphasized somewhat different moral dimensions. Religious and nonreligious participants did not differ in the likelihood or quality of committed moral and immoral acts. Being the target of moral or immoral deeds had the strongest impact on happiness, whereas committing moral or immoral deeds had the strongest impact on sense of purpose. Analyses of daily dynamics revealed evidence for both moral contagion and moral licensing. In sum, morality science may benefit from a closer look at the antecedents, dynamics, and consequences of everyday moral experience.


Becks L.,University of Toronto | Becks L.,University of Cologne | Agrawal A.F.,University of Toronto
Nature | Year: 2010

The evolution and maintenance of sexual reproduction has puzzled biologists for decades. Although this field is rich in hypotheses, experimental evidence is scarce. Some important experiments have demonstrated differences in evolutionary rates between sexual and asexual populations; other experiments have documented evolutionary changes in phenomena related to genetic mixing, such as recombination and selfing. However, direct experiments of the evolution of sex within populations are extremely rare (but see ref. 12). Here we use the rotifer, Brachionus calyciflorus, which is capable of both sexual and asexual reproduction, to test recent theory predicting that there is more opportunity for sex to evolve in spatially heterogeneous environments. Replicated experimental populations of rotifers were maintained in homogeneous environments, composed of either high- or low-quality food habitats, or in heterogeneous environments that consisted of a mix of the two habitats. For populations maintained in either type of homogeneous environment, the rate of sex evolves rapidly towards zero. In contrast, higher rates of sex evolve in populations experiencing spatially heterogeneous environments. The data indicate that the higher level of sex observed under heterogeneity is not due to sex being less costly or selection against sex being less efficient; rather sex is sufficiently advantageous in heterogeneous environments to overwhelm its inherent costs. Counter to some alternative theories for the evolution of sex, there is no evidence that genetic drift plays any part in the evolution of sex in these populations. © 2010 Macmillan Publishers Limited. All rights reserved.


The management of chronic lymphocytic leukemia (CLL) is undergoing profound changes. Several new drugs have been approved for CLL treatment (fludarabine, bendamustine, and the monoclonal antibodies alemtuzumab, rituximab, and ofatumumab) and many more drugs are in advanced clinical development to be approved for this disease. In addition, the extreme heterogeneity of the clinical course and our improved ability to foresee the prognosis of this leukemia by the use of clinical, biological, and genetic parameters now allow us to characterize patients with a very mild onset and course, an intermediate prognosis, or a very aggressive course with high-risk leukemia. Therefore, it becomes increasingly challenging to select the right treatment strategy for each condition. This article summarizes the currently available diagnostic and therapeutic tools and gives an integrated recommendation of how to manage CLL in 2013. Moreover, I propose a strategy how we might integrate the novel agents for CLL therapy into sequential treatment approaches in the near future.


Kohler C.N.,University of Cologne
Journal of Histochemistry and Cytochemistry | Year: 2011

The author has recently reported the distribution of the cytoskeleton-associated protein caldesmon in spleen and lymph nodes detected with different antibodies against caldesmon (J Histochem Cytochem 58:183-193, 2010). Here the author reports the distribution of caldesmon in the CNS and ganglia of the mouse using the same antibodies. Western blot analysis of mouse brain and spinal cord showed the preponderance of l-caldesmon and suggested at least two l-caldesmon isoforms in the brain. Immunostaining revealed the predominant reactivity of smooth muscle cells and cells resembling pericytes of many large and small blood vessels, ependymocytes, and secretory cells of the pineal gland and pituitary gland. Neuronal perikarya and neuropil in general displayed no or weak immunoreactivity, but there was stronger labeling of neuronal perikarya in dorsal root and trigeminal ganglia. In the brain, staining of the neuropil was stronger in the molecular layers of the dentate gyrus and cerebellum. Results show that caldesmon is expressed in many different cell types in the CNS and ganglia, consistent with the notion that lcaldesmon is ubiquitously expressed, but it appears most concentrated in smooth muscle cells, pericytes, epithelial cells, secretory cells, and neuronal perikarya in dorsal root and trigeminal ganglia. © The Author(s) 2011.


Tieke B.,University of Cologne
Current Opinion in Colloid and Interface Science | Year: 2011

The article is concerned with the layer-by-layer (LbL) assembly of electrochromic films using coordinative interactions between compounds. At first the concepts of coordinative supramolecular assembly are explained and examples are presented. Subsequently electrochromic LbL assemblies prepared upon electrostatic and/or coordinative interactions are briefly discussed. In the focus of the article are films of terpyridine(tpy)-functionalized polyiminoarylene metal ion complexes, which are prepared upon coordinative LbL assembly of the tpy-substituted polyiminoarylenes and metal ions. The films exhibit reversible electrochromic behavior with high contrast and fast response times. It is demonstrated that the electrochromic behavior of the films can be modified by a variation of polymer structure, metal ions, and counterions. © 2011 Elsevier Ltd.


Harrison F.E.,Vanderbilt University | Bowman G.L.,Oregon Health And Science University | Polidori M.C.,University of Cologne
Nutrients | Year: 2014

This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer's disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. © 2014 by the authors; licensee MDPI, Basel, Switzerland.


Rabenhorst A.,University of Cologne
Current allergy and asthma reports | Year: 2014

Interleukin-31 (IL-31) is a newly discovered cytokine associated with chronic skin inflammation and pruritus. Patients with atopic dermatitis, chronic spontaneous urticaria, allergic contact dermatitis, prurigo nodularis, primary cutaneous lymphoma and mastocytosis exhibit increased serum levels of IL-31 protein and elevated IL-31 mRNA in the skin. Interestingly, in some of these diseases, IL-31 serum levels correlate with disease activity. In the present review, we particularly focus on studies investigating IL-31 as a novel diagnostic biomarker indicating the severity of allergic diseases. We highlight a recent study on IL-31 in mastocytosis, which reports on elevated serum levels of IL-31 in adults correlating with the severity of disease categories, tryptase levels and percentage of bone marrow infiltration. We conclude that growing knowledge about IL-31, its receptors and signaling pathways serves to better understand the pathogenesis of allergic diseases and may lead to the development of novel treatment approaches.


Ebeling F.,University of Cologne | Lotz S.,Stanford University | Lotz S.,University of Lausanne
Nature Climate Change | Year: 2015

Motivating individuals to choose energy from sustainable sources over conventionally produced power constitutes one of the biggest policy challenges for societies. Here we present the results of a randomized controlled trial in Germany that tested the impact of default rules (that is, a type of "nudging") on voluntary purchases of "green" energy contracts that entirely stem from renewable resources. Setting the default choice to more expensive "green" energy (that is, where consumers have to actively opt out if they do not want it) increased purchases of such nearly tenfold. Furthermore, county-level political preference for the green party uniquely predicted behaviour in the absence of the nudge, suggesting that default setting potentially overrules motivational aspects of green energy purchases. In follow-up experiments, we provide further evidence that the effect does not seem to be driven by unawareness. Summarizing, the present research provides an example of using behavioural science for climate change mitigation and shows alternatives to the use of subsidies or other economic incentives. © 2015 Macmillan Publishers Limited.


Saugel B.,University of Hamburg | Grothe O.,University of Cologne | Grothe O.,Karlsruhe Institute of Technology | Wagner J.Y.,University of Hamburg
Anesthesia and Analgesia | Year: 2015

When comparing 2 technologies for measuring hemodynamic parameters with regard to their ability to track changes, 2 graphical tools are omnipresent in the literature: the 4-quadrant plot and the polar plot recently proposed by Critchley et al. The polar plot is thought to be the more advanced statistical tool, but care should be taken when it comes to its interpretation. The polar plot excludes possibly important measurements from the data. The polar plot transforms the data nonlinearily, which may prevent it from being seen clearly. In this article, we compare the 4-quadrant and the polar plot in detail and thoroughly describe advantages and limitations of each. We also discuss pitfalls concerning the methods to prepare the researcher for the sound use of both methods. Finally, we briefly revisit the Bland-Altman plot for the use in this context. © 2015 International Anesthesia Research Society.


Escobar-Henriques M.,University of Cologne
Cell Research | Year: 2014

Mitochondrial genes including Mfn2 are at the center of many diseases, underscoring their potential as a therapeutical target. The Chen group now identified 15-oxospiramilactone as a chemical inhibitor of the mammalian deubiquitylase USP30, acting on Mfn1 and Mfn2. © 2014 IBCB, SIBS, CAS.


Sigurbjornsdottir S.,1 European Molecular Biology Laboratory | Mathew R.,1 European Molecular Biology Laboratory | Leptin M.,1 European Molecular Biology Laboratory | Leptin M.,University of Cologne
Nature Reviews Molecular Cell Biology | Year: 2014

Many organs contain networks of epithelial tubes that transport gases or fluids. A lumen can be generated by tissue that enwraps a pre-existing extracellular space or it can arise de novo either between cells or within a single cell in a position where there was no space previously. Apparently distinct mechanisms of de novo lumen formation observed in vitro - in three-dimensional cultures of endothelial and Madin-Darby canine kidney (MDCK) cells - and in vivo - in zebrafish vasculature, Caenorhabditis elegans excretory cells and the Drosophila melanogaster trachea - in fact share many common features. In all systems, lumen formation involves the structured expansion of the apical plasma membrane through general mechanisms of vesicle transport and of microtubule and actin cytoskeleton regulation.


The use of artifacts and objects from scientific medical collections and museums for academic teaching purposes are one of the main qualifying tasks of those institutions. In recent years, this aspect of scientific collections has again become on focus within academics. The collections offer a unique chance for visual and haptic forms of teaching in many fields. Due to the potential of scientific collections, educators in all branches in academic learning should be familiar with handling objects for such purposes. © 2015, Springer-Verlag Berlin Heidelberg.


Rising import dependency, increasing market liberalization and cross-border trade and security of supply fears facilitate investments in natural gas supply infrastructures in Europe. In order to ensure an efficient allocation of capital resources, it is important to identify congestion in the existing system and investment requirements based on economic principles. This paper first outlines an analytical framework for the identification of bottlenecks and the evaluation of transport capacities and the cost of congestion based on nodal prices. Secondly, an infrastructure model of the European gas market with high temporal and spatial granularity which exhibits the characteristics of the theoretical model is introduced. Parameterizing the model with the existing infrastructure and applying a demand and supply scenario for the year 2015, congestion mark-ups between countries in Europe are estimated. This approach indicates potential bottlenecks which might arise within the next five years and quantifies their economic costs. With only some temporary congestion, physical market integration is found to be high in Western Europe. In Eastern Europe, severe bottlenecks are identified and discussed. Implications for efficient investment decisions arising from the findings are examined in the context of the theoretical considerations. © 2011 Elsevier Ltd.


Ruschewitz U.,University of Cologne
Angewandte Chemie - International Edition | Year: 2016

Ge-Ge double bonds: The reaction of elemental lithium, sodium, and germanium at 750°C results in the Zintl phase Li3NaGe2, which, according to the Zintl-Klemm concept, contains [Ge=Ge]4- dumbbells with unprecedented short Ge-Ge distances. Based on structural, spectroscopic, and theoretical considerations, convincing evidence is given that Ge-Ge double bonds are in fact present. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Baker M.J.,University of Cologne
Cold Spring Harbor perspectives in biology | Year: 2011

A decline in mitochondrial activity has been associated with aging and is a hallmark of many neurological diseases. Surveillance mechanisms acting at the molecular, organellar, and cellular level monitor mitochondrial integrity and ensure the maintenance of mitochondrial proteostasis. Here we will review the central role of mitochondrial chaperones and proteases, the cytosolic ubiquitin-proteasome system, and the mitochondrial unfolded response in this interconnected quality control network, highlighting the dual function of some proteases in protein quality control within the organelle and for the regulation of mitochondrial fusion and mitophagy.


Zhang H.,Qingdao University of Science and Technology | Tieke B.,University of Cologne
Polymer Chemistry | Year: 2014

Monomers and conjugated polymers based on benzodifuranone, benzodipyrrolidone, naphthodifuranone and naphthodipyrrolidone are reviewed. Synthetic pathways to monomers and polymers, and the characteristic properties such as optical and electrochemical properties, and device properties are described. © 2014 the Partner Organisations.


Khomskii D.I.,University of Cologne
Nature Communications | Year: 2014

The modelling of magnetic monopoles in solids is a hot topic nowadays. Here, I propose that in solids with the linear magnetoelectric effect there should exist, close to electric charges, magnetic textures of magnetic monopole type. Their existence can lead to rather striking consequences, such as (magneto)electric Hall effect, magnetophotovoltaic effect and so on, which can be observed experimentally. In addition, in ordinary magnetoelectric materials not only magnetic monopoles can accompany the charge, but also more complicated local magnetic objects can be created, for example, local toroics, which can also lead to unusual effects in transport and other properties of such systems. © 2014 Macmillan Publishers Limited. All rights reserved.


Viehmann J.,University of Cologne
Energy Policy | Year: 2011

This paper conducts an empirical analysis of risk premiums in the German day-ahead Electricity Wholesale Market. We compare hourly price data of the European Energy Exchange (EEX) auction and of the continuous over-the-counter (OTC) market which takes place prior to the EEX auction. Data provided by the Energy Exchange Austria (EXAA) has been used as a snapshot of the OTC market two hours prior to the EEX auction. Ex post analysis found market participants are willing to pay both significant positive and negative premiums for hourly contracts. The largest positive premiums were paid for high demand evening peak hours on weekdays during winter months. By contrast, night hours on weekends featuring lowest demand levels display negative premiums. Additionally, ex ante analysis found a strong positive correlation between the expected tightness of the system and positive premiums. For this purpose, a tightness factor has been introduced that includes expectations of fundamental factors such as power plant availability, wind power production and demand. Hence, findings by Longstaff and Wang (2004) can be supported that power traders in liberalised markets behave like risk-averse rational economic agents. © 2010 Elsevier Ltd.


Lochner S.,University of Cologne
Journal of Natural Gas Science and Engineering | Year: 2011

Analyzing short-term security of supply or the degree of physical market integration in the European gas market requires models with high spatial and temporal granularity which allow to do so in a comprehensive manner taking interdependencies in the supply infrastructure into account. This paper presents an infrastructure and dispatch model of the European gas market which enables such analyses. The ex-post application of the model to the January 2009 Russia-Ukraine crisis yields that the market's reaction to the crisis was close to the optimal least-cost response implying a very efficient handling of the transit disruption by the gas sector. While large diversions of gas flows from the west to the east were possible, a high dependence on one import route, limited infrastructure flexibility and storage volumes in eastern Europe hampered security of supply in this region. Generally, the results confirm the importance of gas stocks in mitigating risks from supply disruptions as additional storage withdrawals compensated more than two thirds of supply shortfalls during the crisis. Further simulations also demonstrate that increasing flexibility of the transport system (reverse flow capabilities) enhances security of supply for further consumers in eastern Europe, but not for all of them. © 2011 Elsevier B.V.


Cornely O.A.,University of Cologne
Clinical Microbiology and Infection | Year: 2012

Until recently, treatment of Clostridium difficile infection (CDI) was mainly limited to oral metronidazole and vancomycin, neither of which is optimal. Up to 25% of patients with CDI experience recurrence of infection within 30days following treatment with these agents, while c.45-65% of these patients experience further (and sometimes multiple) recurrences. Recurrent CDI represents a major treatment challenge for which new therapeutic options are sorely needed. Fidaxomicin is a first-in-class, oral macrocyclic antibiotic with targeted bactericidal activity against C. difficile and minimal effect on the constituents of the normal colonic microflora. This microflora-sparing activity allows for more rapid restoration of the normal colonic microflora in patients with CDI. In two separate, but almost identical, phase 3 clinical trials in which patients with CDI were treated with either fidaxomicin or vancomycin, fidaxomicin demonstrated superior clinical outcomes in comparison with the current best available treatment. While non-inferiority was demonstrated with respect to rates of clinical cure at end of treatment, significantly fewer fidaxomicin-treated patients experienced disease recurrence, which translated into clinically significant improvements in sustained clinical cure. Subsequent sub-population analyses suggest that these benefits extend to older patients, patients with severe CDI, renally impaired patients and patients with a prior episode of CDI. For CDI patients receiving concomitant antibiotics, fidaxomicin achieved significantly better rates of clinical cure and sustained clinical cure than vancomycin recipients. Fidaxomicin has a safety profile similar to oral vancomycin and appears generally well tolerated. Fidaxomicin represents an important addition to current treatment options for CDI. © 2012 The Author Clinical Microbiology and Infection © 2012 European Society of Clinical Microbiology and Infectious Diseases.


Illingworth C.J.R.,Wellcome Trust Sanger Institute | Parts L.,Wellcome Trust Sanger Institute | Schiffels S.,University of Cologne | Liti G.,University of Nice Sophia Antipolis | Mustonen V.,Wellcome Trust Sanger Institute
Molecular Biology and Evolution | Year: 2012

When selection is acting on a large genetically diverse population, beneficial alleles increase in frequency. This fact can be used to map quantitative trait loci by sequencing the pooled DNA from the population at consecutive time points and observing allele frequency changes. Here, we present a population genetic method to analyze time series data of allele frequencies from such an experiment. Beginning with a range of proposed evolutionary scenarios, the method measures the consistency of each with the observed frequency changes. Evolutionary theory is utilized to formulate equations of motion for the allele frequencies, following which likelihoods for having observed the sequencing data under each scenario are derived. Comparison of these likelihoods gives an insight into the prevailing dynamics of the system under study. We illustrate the method by quantifying selective effects from an experiment, in which two phenotypically different yeast strains were first crossed and then propagated under heat stress (Parts L, Cubillos FA, Warringer J, et al. [14 co-authors]. 2011. Revealing the genetic structure of a trait by sequencing a population under selection. Genome Res). From these data, we discover that about 6% of polymorphic sites evolve nonneutrally under heat stress conditions, either because of their linkage to beneficial (driver) alleles or because they are drivers themselves. We further identify 44 genomic regions containing one or more candidate driver alleles, quantify their apparent selective advantage, obtain estimates of recombination rates within the regions, and show that the dynamics of the drivers display a strong signature of selection going beyond additive models. Our approach is applicable to study adaptation in a range of systems under different evolutionary pressures. © The Author(s).


Hanisch F.-G.,University of Cologne
Methods in Molecular Biology | Year: 2011

This paper describes a cyclic on-column procedure for the sequential degradation of complex O-glycans on proteins by periodate oxidation of sugars and cleavage of oxidation products by elimination. Glycoproteins are immobilized to alkali-stable, reversed-phase Poros 20 beads, desialylated by treatment with dilute trifluoroacetic acid, and de-O-glycosylated by two degradation cycles before the eluted apoproteins are digested with trypsin for analysis by liquid chromatography electrospray ionizationmass spectrometry. Even complex glycan moieties are removed under mild conditions with only minimal effects on structural integrity of the peptide core by fragmentation, dehydration, or racemization of lysine and arginine residues. The protocol is also applicable on gel-immobilized glycoproteins after 1D or 2D gel electrophoresis. Conversion of O-glycoproteins into their corresponding apoproteins results in facilitated accessibility of tryptic cleavage sites, increases the numbers of peptide fragments, and accordingly enhances protein coverage and identification rates within the subproteome of mucin-type O-glycoproteins. The protocol is suitable for automatization, but due to partial elution from the Poros 20 columns it is not recommended for applications on the glycopeptide level. © Springer Science+Business Media, LLC 2011.


Balafoutas L.,University of Innsbruck | Nikiforakis N.,Abu Dhabi University | Rockenbach B.,University of Cologne
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

Many interactions in modern human societies are among strangers. Explaining cooperation in such interactions is challenging. The two most prominent explanations critically depend on individuals' willingness to punish defectors: In models of direct punishment, individuals punish antisocial behavior at a personal cost, whereas in models of indirect reciprocity, they punish indirectly by withholding rewards. We investigate these competing explanations in a field experiment with real-life interactions among strangers. We find clear evidence of both direct and indirect punishment. Direct punishment is not rewarded by strangers and, in line with models of indirect reciprocity, is crowded out by indirect punishment opportunities. The existence of direct and indirect punishment in daily life indicates the importance of both means for understanding the evolution of cooperation.


Hoppe B.,University of Cologne
Nature Reviews Nephrology | Year: 2012

The autosomal recessive inherited primary hyperoxalurias types I, II and III are caused by defects in glyoxylate metabolism that lead to the endogenous overproduction of oxalate. Type III primary hyperoxaluria was first described in 2010 and further types are likely to exist. In all forms, urinary excretion of oxalate is strongly elevated (>1 mmol/1.73 m2 body surface area per day; normal <0.5 mmol/1.73 m2 body surface area per day), which results in recurrent urolithiasis and/or progressive nephrocalcinosis. All entities can induce kidney damage, which is followed by reduced oxalate elimination and consequent systemic deposition of calcium oxalate crystals. Systemic oxalosis should be prevented, but diagnosis is all too often missed or delayed until end-stage renal disease (ESRD) occurs; this outcome occurs in >30% of patients with primary hyperoxaluria type I. The fact that such a large proportion of patients have such poor outcomes is particularly unfortunate as ESRD can be delayed or even prevented by early intervention. Treatment options for primary hyperoxaluria include alkaline citrate, orthophosphate, or magnesium. In addition, pyridoxine treatment can be used to normalize or reduce oxalate excretion in about 30% of patients with primary hyperoxaluria type I. Time on dialysis should be short to avoid overt systemic oxalosis. Transplantation methods depend on the type of primary hyperoxaluria and on the particular patient, but combined liver and kidney transplantation is the method of choice in patients with primary hyperoxaluria type I and isolated kidney transplantation is the preferred method in those with primary hyperoxaluria type II. To the best of our knowledge, progression to ESRD has not yet been reported in any patient with primary hyperoxaluria type III. © 2012 Macmillan Publishers Limited. All rights reserved.


Ros R.,University of Valencia | Munoz-Bertomeu J.,University of Valencia | Munoz-Bertomeu J.,Institute Biologia Molecular Y Celular Of Plantas Ibmcp | Krueger S.,University of Cologne
Trends in Plant Science | Year: 2014

Serine (Ser) has a fundamental role in metabolism and signaling in living organisms. In plants, the existence of different pathways of Ser biosynthesis has complicated our understanding of this amino acid homeostasis. The photorespiratory glycolate pathway has been considered to be of major importance, whereas the nonphotorespiratory phosphorylated pathway has been relatively neglected. Recent advances indicate that the phosphorylated pathway has an important function in plant metabolism and development. Plants deficient in this pathway display developmental defects in embryos, male gametophytes, and roots. We propose that the phosphorylated pathway is more important than was initially thought because it is the only Ser source for specific cell types involved in developmental events. Here, we discuss its importance as a link between metabolism and development in plants. © 2014 Elsevier Ltd.


Elgar F.J.,McGill University | Pfortner T.-K.,University of Cologne | Moor I.,Martin Luther University of Halle Wittenberg | De Clercq B.,Ghent University | And 2 more authors.
The Lancet | Year: 2015

Background Information about trends in adolescent health inequalities is scarce, especially at an international level. We examined secular trends in socioeconomic inequality in five domains of adolescent health and the association of socioeconomic inequality with national wealth and income inequality. Methods We undertook a time-series analysis of data from the Health Behaviour in School-aged Children study, in which cross-sectional surveys were done in 34 North American and European countries in 2002, 2006, and 2010 (pooled n 492 788). We used individual data for socioeconomic status (Health Behaviour in School-aged Children Family Affluence Scale) and health (days of physical activity per week, body-mass index Z score [zBMI], frequency of psychological and physical symptoms on 0-5 scale, and life satisfaction scored 0-10 on the Cantril ladder) to examine trends in health and socioeconomic inequalities in health. We also investigated whether international differences in health and health inequalities were associated with per person income and income inequality. Findings From 2002 to 2010, average levels of physical activity (3·90 to 4·08 days per week; p<0·0001), body mass (zBMI -0·08 to 0·03; p<0·0001), and physical symptoms (3·06 to 3·20, p<0·0001), and life satisfaction (7·58 to 7·61; p=0·0034) slightly increased. Inequalities between socioeconomic groups increased in physical activity (-0·79 to -0·83 days per week difference between most and least affluent groups; p=0·0008), zBMI (0·15 to 0·18; p<0·0001), and psychological (0·58 to 0·67; p=0·0360) and physical (0·21 to 0·26; p=0·0018) symptoms. Only in life satisfaction did health inequality fall during this period (-0·98 to -0·95; p=0·0198). Internationally, the higher the per person income, the better and more equal health was in terms of physical activity (0·06 days per SD increase in income; p<0·0001), psychological symptoms (-0·09; p<0·0001), and life satisfaction (0·08; p<0·0001). However, higher income inequality uniquely related to fewer days of physical activity (-0·05 days; p=0·0295), higher zBMI (0·06; p<0·0001), more psychological (0·18; p<0·0001) and physical (0·16; p<0·0001) symptoms, and larger health inequalities between socioeconomic groups in psychological (0·13; p=0·0080) and physical (0·07; p=0·0022) symptoms, and life satisfaction (-0·10; p=0·0092). Interpretation Socioeconomic inequality has increased in many domains of adolescent health. These trends coincide with unequal distribution of income between rich and poor people. Widening gaps in adolescent health could predict future inequalities in adult health and need urgent policy action. Funding Canadian Institutes of Health Research. © 2015 Elsevier Ltd.


Fauser S.,University of Cologne | Lambrou G.N.,Institute Of La Vision
Survey of Ophthalmology | Year: 2015

Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have proven efficacy at a study-population level, although individual patient responses vary, with most of the patients responding well to anti-VEGF therapies, while a few respond poorly. The pathogenesis of AMD is known to have a genetic component, but it is unclear if any particular genotype can predict response to anti-VEGF therapy. With the advent of less expensive genotyping technology, there have been numerous studies within this area. Here we analyze potential biomarker candidates identified that could be used in a clinical setting to predict response to anti-VEGF treatment of nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39 publications. The SNPs that appeared to be of most importance fell into two main groups: those previously associated with AMD pathogenesis and those within the signaling pathway targeted by anti-VEGF therapies. A number of small studies found evidence supporting an association between anti-VEGF treatment response and two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized controlled trials found no such association. It is possible that, in the future, the cumulative effect of several high-risk SNPs may prove useful in a clinical setting and that other genetic biomarkers may emerge. © 2015 Elsevier Inc.


Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

In a previous work we have proposed that the Prokushkin-Vasiliev higher spin N = 2 supergravity on AdS3 is dual to a large N limit of the N = (2,2) ℂPN Kazama- Suzuki model. There is now strong evidence supporting this proposal based on symmetry and spectrum comparison. In this paper we will give further evidence for the duality by studying correlation functions. We compute boundary three point functions with two fermionic operators and one higher spin bosonic current in terms of the bulk supergravity theory. Then we compare with the results in the dual CFT, where the supersymmetry of the theory turns out to be very helpful. In particular we use it to confirm results conjectured in the bosonic case. Moreover, correlators with a fermionic current can be obtained via supersymmetry. © 2013 SISSA, Trieste, Italy.


Creutzig T.,TU Darmstadt | Hikida Y.,Keio University | Ronne P.B.,University of Cologne
Journal of High Energy Physics | Year: 2013

We propose a duality between a higher spin N=1 supergravity on AdS 3 and a large N limit of a family of N=(1,1) superconformal field theories. The gravity theory is an N=1 truncation of the N=2 supergravity found by Prokushkin and Vasiliev, and the dual conformal field theory is defined by a supersymmetric coset model. We check this conjecture by comparing one loop partition functions and find agreement. Moreover, we study the symmetry of the dual coset model and in particular compute fields of the coset algebra of dimension 3/2, 2, 2 and 5/2 explicitly. © 2013 SISSA, Trieste, Italy.


Sawicki P.T.,University of Cologne
Diabetologia | Year: 2012

This commentary discusses whether screening for type 2 diabetes or earlier normalisation of blood glucose levels or initiation of non-antihyperglycaemic agents or any other diabetes-specific treatment can help reduce the excess associated risks for macrovascular morbidity and mortality. The available data indicate that screening with the sole aim of decreasing the lead time between diagnosis and treatment is very unlikely to reduce these risks. In contrast to macrovascular complications, some microvascular events such as background retinopathy could theoretically be prevented by earlier diagnosis and better glycaemic control, particularly in relatively young type 2 diabetic patients. This, however, remains to be shown in controlled prospective intervention trials. © Springer-Verlag 2012.


Ringe J.D.,University of Cologne | Kipshoven C.,MADAUS GmbH
Dermato-Endocrinology | Year: 2012

Background: Vitamin D insufficiency is increasingly recognized as an important risk factor in the pathogenesis of falls and fractures and may increase the risk of other diseases. The aim of this study was to obtain information about the vitamin D supply from a representative cohort of the German population. Methods: 264 General practitioners participated in the DeViD-Trial (D-Vitamin in Deutschland) by taking blood samples from their consenting daily ambulant patients regardless of the actual reason for consultation. In these blood samples vitamin D [25(OH)D] and other related parameters were measured at a central laboratory. The patients filled in a simple questionnaire (i.e., age, sex, etc.). The trial was performed between February 26 and May 25, 2007. Results: Laboratory and personal data were documented for 1,343 individuals (615 men, 728 women). The age distribution ranged from 20 to 99 y, the mean age of the whole cohort was 57.6 y (men 58.2, women 57.2). The mean 25- OH-D-value for the whole cohort was 16.2 ng/ml (range: 6.0 to 66.8, median 14.1 ng/ml). Ten percent of the patients had 25(OH)D-values below 7 ng/ml, 65% below 20 ng/ml and 92% showed values below 30 ng/ml. In the more recent literature, 25(OH)D values below 30 ng/ml are regarded as sub-optimal for bone, muscle and general health. Correspondingly it can be stated that in this representative population there is a high prevalence of moderate to severe vitamin D-insufficiency regardless of young or old age. © 2012 Landes Bioscience.


Roth G.,University of Bremen | Walkowiak W.,University of Cologne
Cold Spring Harbor Perspectives in Biology | Year: 2015

In amphibians, nerve cell size is highly correlated with genome size, and increases in genome and cell size cause a retardation of the rate of development of nervous (as well as nonnervous) tissue leading to secondary simplification. This yields an inverse relationship between genome and cell size on the one hand and morphological complexity of the tectum mesencephali as the main visual center, the size of the torus semicircularis as the main auditory center, the size of the amphibian papilla as an important peripheral auditory structure, and the size of the cerebellum as a major sensorimotor center. Nervous structures developing later (e.g., torus and cerebellum) are more affected by secondary simplification than those that develop earlier (e.g., the tectum). This effect is more prominent in salamanders and caecilians than in frogs owing to larger genome and cells sizes in the former two taxa. We hypothesize that because of intragenomic evolutionary processes, important differences in brain morphology can arise independently of specific environmental selection. © 2015 Cold Spring Harbor Laboratory Press. All rights reserved.


Schilbach L.,Max Planck Institute of Psychiatry | Schilbach L.,University of Cologne
Current Opinion in Behavioral Sciences | Year: 2015

The gaze of others fascinates us from birth onwards. Traditionally, experimental approaches to study the effects of gaze have focused on how human observers respond to gaze cues and how attention, perception and action control is influenced by them. In recent years, the investigation of gaze behavior has moved toward the inclusion of more ecologically valid conditions, in which gaze signals are exchanged as part of an ongoing reciprocal social interaction. Such an 'interactive turn' is beginning to yield new insights into the behavioral dynamics and neural mechanisms of gaze behavior as they unfold in real life. © 2015 Elsevier Ltd.


Wallbach M.,University of Cologne
Journal of Hypertension | Year: 2016

BACKGROUND:: Both baroreflex activation therapy (BAT) and renal denervation modulate sympathetic activity. The aim of this study was to systematically investigate whether additive modulation of autonomic nervous system by BAT lowers blood pressure (BP) in patients who still suffer from uncontrolled resistant hypertension despite prior renal denervation. METHODS:: From 2012 to January 2015, patients treated with BAT for uncontrolled resistant hypertension, who prior received renal denervation were consecutively analyzed in four German centers for hypertension. Analyses of office BP, 24-h ambulatory BP, central hemodynamics, parameters of renal function were performed. RESULTS:: A total of 28 patients, who underwent renal denervation at least 5 months before and still suffer from uncontrolled BP, were subsequently treated with BAT. The office SBP decreased from 182?±?28 to 163?±?27?mmHg (P?


Kohler C.,University of Cologne
Acta Neuropathologica | Year: 2016

Granule-containing vacuoles in the cytoplasm of hippocampal neurons are a neuropathological feature of Alzheimer’s disease. Granulovacuolar degeneration (GVD) is not disease-specific and can be observed in other neurodegenerative disorders and even in the brains of non-demented elderly people. However, several studies have reported much higher numbers of neurons undergoing GVD in the hippocampus of Alzheimer’s disease cases. Recently, a neuropathological staging system for GVD has facilitated neuropathological assessment. Data obtained by electron microscopy and immunolabeling suggest that GVD inclusions are a special form of autophagic vacuole. GVD frequently occurs together with pathological changes of the microtubule-associated protein tau, but to date, the relationship between the two lesions remains elusive. Originally identified in hematoxylin- and silver-stained sections, immunolabeling has shown that the granules are composed of a variety of proteins, including those related to tau pathology, autophagy, diverse signal transduction pathways, cell stress and apoptosis. Several of these proteins serve as markers of GVD. Most researchers and authors have interpreted the sequestration of proteins into GVD inclusions as either a cellular defense mechanism or one that leads to the impairment of important cellular functions. This review provides a detailed overview of the various aspects of GVD and focuses on the relationship between tau pathology and GVD. © 2016 Springer-Verlag Berlin Heidelberg


Cheng L.E.,University of California at San Francisco | Hartmann K.,University of Cologne | Roers A.,Carl Gustav Carus Institute | Krummel M.F.,University of California at San Francisco | Locksley R.M.,Howard Hughes Medical Institute
Immunity | Year: 2013

Mast cells are tissue-resident immune cells that play a central role in allergic disease. These contributions are largely dependent on the acquisition of antigen-specific immunoglobulin E (IgE). Despite this requirement, studies of mast cell and IgE interactions have overlooked the mechanism by which mast cells acquire IgE from the blood. To address this gap, we developed reporter IgE molecules and employed imaging techniques to study mast cell function in situ. Our data demonstrate that skin mast cells exhibit selective uptake of IgE based on perivascular positioning. Furthermore, perivascular mast cells acquire IgE by extending cell processes across the vessel wall to capture luminal IgE. These data demonstrate how tissue mast cells acquire IgE and reveal a strategy by which extravascular cells monitor blood contents to capture molecules central to cellular function. © 2013 Elsevier Inc.


Kumar S.,University of Edinburgh | Schiffer P.H.,University of Cologne | Blaxter M.,University of Edinburgh
Nucleic Acids Research | Year: 2012

Genome sequencing has been democratized by second-generation technologies, and even small labs can sequence metazoan genomes now. In this article, we describe '959 Nematode Genomes' - a community-curated semantic wiki to coordinate the sequencing efforts of individual labs to collectively sequence 959 genomes spanning the phylum Nematoda. The main goal of the wiki is to track sequencing projects that have been proposed, are in progress, or have been completed. Wiki pages for species and strains are linked to pages for people and organizations, using machine- and humanreadable metadata that users can query to see the status of their favourite worm. The site is based on the same platform that runs Wikipedia, with semantic extensions that allow the underlying taxonomy and data storage models to be maintained and updated with ease compared with a conventional database-driven web site. The wiki also provides a way to track and share preliminary data if those data are not polished enough to be submitted to the official sequence repositories. In just over a year, this wiki has already fostered new international collaborations and attracted newcomers to the enthusiastic community of nematode genomicists. www.nematodegenomes.org. © The Author(s) 2011. Published by Oxford University Press.


Bauer A.,TU Munich | Garst M.,University of Cologne | Pfleiderer C.,TU Munich
Physical Review Letters | Year: 2013

We report high-precision measurements of the temperature and magnetic field dependence of the specific heat, C(T,H), across the magnetic phase diagram of MnSi. Clear anomalies establish the Skyrmion lattice unambiguously as a thermodynamic phase. The evolution of the specific heat anomalies, the field dependence of the entropy released at the phase transitions, and the temperature versus field dependence of crossover lines provide striking evidence of a tricritical point at μ0HTCPint=340 mT and TTCP=28.5 K. The existence of this tricritical point represents strong support of a helimagnetic Brazovskii transition, i.e., a fluctuation-induced first-order transition at H=0. © 2013 American Physical Society.


Jahnke S.,TU Dresden | Imhoff R.,University of Cologne | Hoyer J.,TU Dresden
Archives of Sexual Behavior | Year: 2015

Despite productive research on stigma and its impact on people’s lives in the past 20 years, stigmatization of people with pedophilia has received little attention. We conducted two surveys estimating public stigma and determining predictors of social distance from this group. In both studies, pedophilia was defined as a “dominant sexual interest in children.” The survey was comprised of items measuring agreement with stereotypes, emotions, and social distance (among others). Responses were compared with identical items referring to either people who abuse alcohol (Study 1), sexual sadists or people with antisocial tendencies (Study 2). Study 1 was conducted in two German cities (N = 854) and Study 2 sampled 201 English-speaking online participants. Both studies revealed that nearly all reactions to people with pedophilia were more negative than those to the other groups, including social distance. Fourteen percent (Study 1) and 28 % (Study 2) of the participants agreed that people with pedophilia should better be dead, even if they never had committed criminal acts. The strongest predictors of social distance towards people with pedophilia were affective reactions to this group (anger and, inversely, associated, pity) and the political attitude of right-wing authoritarianism (Study 1). Results strongly indicate that people with pedophilia are a stigmatized group who risk being the target of fierce discrimination. We discuss this particular form of stigmatization with respect to social isolation of persons with pedophilia and indirect negative consequences for child abuse prevention. © 2014, Springer Science+Business Media New York.


Behrens M.,German Institute of Human Nutrition | Korsching S.I.,University of Cologne | Meyerhof W.,German Institute of Human Nutrition
Molecular biology and evolution | Year: 2014

Bitter taste perception in vertebrates relies on a variable number of bitter taste receptor (Tas2r) genes, ranging from only three functional genes in chicken to as many as approximately 50 in frogs. Humans possess a medium-sized Tas2r repertoire encoding three broadly and several narrowly tuned receptors plus receptors with intermediate tuning properties. Such tuning information is not available for bitter taste receptors of other vertebrate species. In particular it is not known, whether a small Tas2r repertoire may be compensated for by broad tuning of these receptors, and on the other side, whether a large repertoire might entail a preponderance of narrowly tuned receptors. To elucidate this question, we cloned all three chicken Tas2rs, the two turkey Tas2rs, three zebra finch Tas2rs, and six Tas2rs of the Western clawed frog representative of major branches of the phylogenetic tree, and screened them with 46 different bitter compounds. All chicken and turkey Tas2rs were broadly tuned, the zebra finch Tas2rs were narrowly tuned, and frog Tas2rs ranged from broadly to narrowly tuned receptors. We conclude that a low number of functional Tas2r genes does not imply a reduced importance of bitter taste per se, as it can be compensated by large tuning width. A high number of functional Tas2r genes appears to allow the evolution of specialized receptors, possibly for toxins with species-specific relevance. In sum, we show that variability in tuning breadth, overlapping agonist profiles, and staggered effective agonist concentration ranges are shared features of human and other vertebrate Tas2rs. © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.


Chandler J.W.,University of Cologne
Trends in Plant Science | Year: 2011

Lateral organs arise from individual or groups of cells either on the flanks of meristems or within defined cellular positional contexts. The first event in organogenesis is founder cell specification. Auxin is one necessary signal in different organ specification contexts, but it is difficult to distinguish between correlative and causal signals and evidence is emerging that other signals exist and that the interplay between these signals is important for organ initiation. This review analyses the progress in understanding which signals contribute to founder cell specification and outlines the emerging complexities in the perception of positional information that are context-dependent and reliant on the establishment and coordination of different types of competencies. © 2011 Elsevier Ltd.


Karenberg A.,University of Cologne
Progress in Brain Research | Year: 2015

Few musicians who suffered from any kind of serious neuropsychiatric problems were able to create works that are still admired today. This new research will show that Frédéric Chopin, who reinvented piano music in the first half of the nineteenth century, was one of those few. He died in Paris aged only 39. While the somatic illness that killed him continues to generate speculation, his recurrent depressive mood swings have remained largely unexamined. A few neuropsychiatric publications make a simplistic effort to assign his emotional condition to a modern diagnostic category, e.g., temporal lobe epilepsy. Because it is impossible to prove such hypotheses, these studies are nothing more than erudite speculation. This chapter will instead incorporate the cultural and medical context of the first half of the nineteenth century in order to explore new possibilities for medical biographies of musicians. © 2015 Elsevier B.V.


Brandt M.C.,Paracelsus Medical University | Reda S.,Paracelsus Medical University | Mahfoud F.,Universitatsklinikum des Saarlandes | Lenski M.,Universitatsklinikum des Saarlandes | And 3 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: This study investigated the effect of catheter-based renal sympathetic denervation (RD) on central hemodynamics in patients with resistant hypertension. Background: High central blood pressure (BP) increases cardiovascular events and mortality independently of peripheral BP. The effect of RD on central BP is unclear. Methods: A total of 110 patients underwent bilateral RD. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressure and hemodynamic indices at baseline and 1, 3, and 6 months after ablation. Ten patients with resistant hypertension not undergoing RD served as controls. Results: RD significantly reduced mean central aortic BP from 167/92 mm Hg to 149/88 mm Hg, 147/85 mm Hg, and 141/85 mm Hg at 1, 3, and 6 months (p < 0.001), respectively. Aortic pulse pressure decreased from 76.2 ± 23.3 mm Hg to 61.5 ± 17.5 mm Hg, 62.7 ± 18.1 mm Hg, and 54.5 ± 15.7 mm Hg 1, 3, and 6 months after RD (p < 0.001), respectively. Six months after RD aortic augmentation and augmentation index were significantly reduced by -11 mm Hg (p < 0.001) and -5.3% (p < 0.001), respectively. Carotid to femoral pulse wave velocity showed a significant reduction from 11.6 ± 3.2 m/s to 9.6 ± 3.1 m/s at 6 months (p < 0.001). Consistently, ejection duration and aortic systolic pressure load were significantly diminished, indicating improvement of cardiac work load by RD. No significant changes were obtained in control patients. Conclusions: Besides the known effect of RD on brachial blood pressure, the study showed for the first time that this novel approach significantly improves arterial stiffness and central hemodynamics, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk. © 2012 American College of Cardiology Foundation.


Messing R.,Heinrich Heine University Dusseldorf | Schmidt A.M.,Heinrich Heine University Dusseldorf | Schmidt A.M.,University of Cologne
Polymer Chemistry | Year: 2011

Significant advances in the field of responsive hydrogels have been achieved by the combination of soft, gel-based matrices with the unique functions of inorganic or biological nanostructures. Like in many biological tissues, the components of such hybrid materials often have converse, yet complementary properties. The possibility of forming self-assembled and supramolecular morphologies from organic polymers in combination with inorganic nanoparticles or biological motifs is of interest for gels with new response properties. A variety of complex gel structures with unique chemical, physical, and biological properties have been engineered or discovered at the nanoscale. In this review, we highlight recent accomplishments and trends in the field of hybrid polymer hydrogels with a focus on approaches towards soft, yet tough shape-changing and actuating materials. We conclude with an outline on future directions and challenges that have to be faced in the design and application of hybrid hydrogels. © The Royal Society of Chemistry.


Zuccaro A.,Max Planck Institute for Terrestrial Microbiology | Zuccaro A.,University of Cologne | Lahrmann U.,Max Planck Institute for Terrestrial Microbiology | Langen G.,Justus Liebig University
Current Opinion in Plant Biology | Year: 2014

Plants associate with a wide range of beneficial fungi in their roots which facilitate plant mineral nutrient uptake in exchange for carbohydrates and other organic metabolites. These associations play a key role in shaping terrestrial ecosystems and are widely believed to have promoted the evolution of land plants. To establish compatibility with their host, root-associated fungi have evolved diverse colonization strategies with distinct morphological, functional and genomic specializations as well as different degrees of interdependence. They include obligate biotrophic arbuscular mycorrhizal (AM), and facultative biotrophic ectomycorrhizal (ECM) interactions but are not restricted to these well-characterized symbioses. There is growing evidence that root endophytic associations, which due to their inconspicuous nature have been often overlooked, can be of mutualistic nature and represent important players in natural and managed environments. Recent research into the biology and genomics of root associations revealed fascinating insight into the phenotypic and trophic plasticity of these fungi and underlined genomic traits associated with biotrophy and saprotrophy. In this review we will consider the commonalities and differences of AM and ECM associations and contrast them with root endophytes. © 2014 The Authors.


Roth S.,University of Cologne
Development Genes and Evolution | Year: 2011

Driesch's statement, made around 1900, that the physics and chemistry of his day were unable to explain self-regulation during embryogenesis was correct and could be extended until the year 1972. The emergence of theories of self-organisation required progress in several areas including chemistry, physics, computing and cybernetics. Two parallel lines of development can be distinguished which both culminated in the early 1970s. Firstly, physicochemical theories of self-organisation arose from theoretical (Lotka 1910-1920) and experimental work (Bray 1920; Belousov 1951) on chemical oscillations. However, this research area gained broader acceptance only after thermodynamics was extended to systems far from equilibrium (1922-1967) and the mechanism of the prime example for a chemical oscillator, the Belousov-Zhabotinski reaction, was deciphered in the early 1970s. Secondly, biological theories of self-organisation were rooted in the intellectual environment of artificial intelligence and cybernetics. Turing wrote his The chemical basis of morphogenesis (1952) after working on the construction of one of the first electronic computers. Likewise, Gierer and Meinhardt's theory of local activation and lateral inhibition (1972) was influenced by ideas from cybernetics. The Gierer-Meinhardt theory provided an explanation for the first time of both spontaneous formation of spatial order and of self-regulation that proved to be extremely successful in elucidating a wide range of patterning processes. With the advent of developmental genetics in the 1980s, detailed molecular and functional data became available for complex developmental processes, allowing a new generation of data-driven theoretical approaches. Three examples of such approaches will be discussed. The successes and limitations of mathematical pattern formation theory throughout its history suggest a picture of the organism, which has structural similarity to views of the organic world held by the philosopher Immanuel Kant at the end of the eighteenth century. © 2011 The Author(s).


Hank K.,University of Cologne
Journals of Gerontology - Series B Psychological Sciences and Social Sciences | Year: 2011

Objectives. We estimate comparable prevalence estimates of "successful aging" for 14 European countries and Israel, adding a new cross-nationally comparative perspective to recently published findings for the United States. Methods. Measures for a variety of specific successful aging criteria were derived from baseline interviews of respondents aged 65+ who participated in the Survey of Health, Ageing, and Retirement in Europe (n = 21,493). A multivariate logistic model was run for our global successful aging measure. Results. Our analysis revealed substantial cross-country variation around a mean value of 8.5%: Although as many as 21.1% of older Danes meet our successful aging criteria, the respective proportion in Poland is only 1.6%. Age, gender, and socioeconomic status are shown to bear highly significant associations with individuals' odds of successful aging. Discussion. The observed cross-national variation in successful aging-which continues to exist if population composition is controlled for-highlights the importance of taking into consideration structural factors at the societal level. It also suggests a potential for policy interventions supporting individuals' opportunities for successful aging. © The Author 2010.


Uthicke S.,Australian Institute of Marine Science | Altenrath C.,University of Cologne
Limnology and Oceanography | Year: 2010

In situ growth of two abundant diatom-bearing benthic foraminiferal species (Amphistegina radiata, Heterostegina depressa) was investigated to elucidate whether differences in abundance between inshore and offshore reefs are influenced by water quality. Five experiments were conducted over 2 yr, comparing growth rates of foraminifera at inshore coral reefs, which are exposed to terrestrial runoff, with those at reefs further offshore. Concentrations of most dissolved and particulate water quality variables were significantly higher inshore and during periods of high runoff (summer wet season). Foraminiferal growth was generally significantly lower on inshore reefs than offshore reefs, and growth of both species was reduced during the wet season. Depth transplantations confirmed that light was not an important factor in growth regulation. In contrast, multiple regression analyses of the effects of water quality variables on foraminiferal growth explained 69% of the variance in growth for A. radiata and 78% for H. depressa. Increased concentrations of dissolved nitrogen were associated with reduced growth. Intracellular carbon-to-nitrogen ratios in the foraminifera also reflected patterns in water quality, with generally lower values in foraminifera from inshore or during periods of high runoff, driven by higher intracellular N contents during these periods. It is suggested that increased nutrient availability releases foraminiferal symbionts from nutrient limitation. This may lead to reduced translocation of organic carbon to the host and resulting reduced host growth. © 2010, by the American Society of Limnology and Oceanography, Inc.


Bothe H.,University of Cologne
Symbiosis | Year: 2012

Although salt has detrimental effects on spore germination of arbuscular mycorrhizal fungi (AMF), their hyphal growth and the colonization rate of plants under laboratory conditions, many salt tolerant plants (the halophytes) are strongly colonized by AMF in their natural habitats. AMF spores in several saline soils consist of to up to 80 % of one single species, Glomus geosporum. In contrast, roots of halophytes are mostly colonized by fungi of the Glomus intraradices group, of which many are as yet uncultured. Salt stress is intimately related to drought in saline habitats. Molecular analyses of genes expressed upon salt stress indicate that aquaporins which facilitate the transfer of water across membranes play a major role in alleviating salt stress in plants. In AMF, genes serving to scavenge reactive oxygen species (ROS) are expressed upon exposure to salt, indicating that fungi have to develop an enhanced oxidative defence. The development of AMF inocula that confer sustained salt tolerance to plants would have enormous practical applications. Many positive reports on salt stress alleviation by AMF exist. However, the state of the art has not yet reached field applications. In contrast to other recent reviews, the present article focuses on ecological aspects of the symbiosis between AMF and halophytes. It also emphasizes the complexity of the interactions between salt and drought stress as well as the role of AMF in alleviating salt stress. © 2012 Springer Science+Business Media Dordrecht.


Greiner C.,University of Cologne
Africa | Year: 2011

Rural-urban migration and networks are fundamental for many livelihoods in sub-Saharan Africa. Remittances in cash and kind provide additional income, enhance food security and offer access to viable resources in both rural and urban areas. Migration allows the involved households to benefit from price differences between rural and urban areas. In this contribution, I demonstrate that rural-urban networks not only contribute to poverty alleviation and security, but also further socio-economic stratification. This aspect has been ignored or neglected by most scholars and development planners. Using ethnographic data from Namibia, I have adopted a translocal perspective on migration and stratification, focusing on the resulting impact in rural areas where modern urban forms of stratification, induced by education and income from wage labour, are on the increase. © 2011 International African Institute.


The German Middle Paleolithic is marked by two stages with abundant archaeological sites: The Eemian Interglacial (MIS 5e) and the Weichselian Interpleniglacial (MIS 3). On the other hand, several stages were seemingly void of any human population (the second half of MIS 6 and MIS 4) and two long periods (MIS 8-6 and MIS 5d-5a) delivered very few archaeological sites, so far. The majority of all assemblages seem to belong to the latest part of the Middle Paleolithic, during the first half of MIS 3. Concerning this period, the layer G stratigraphic complex ("G-Komplex") of Sesselfelsgrotte yielded the longest cultural sequence of late Middle Paleolithic unifacial-plus-bifacial industries (Keilmessergruppen, Micoquian in the sense of a "Mousterian with a Micoquian option", MMO) in Central Europe. Information from this sequence permitted a reconsideration of the internal structure and the dating of the MMO. Evidence is presented for an earlier MMO stage with almost no Levallois technology (MMO-A) and a later stage (MMO-B) with Levallois technology, both occurring at the very end of the European Middle Paleolithic, between 60,000 and 43,000 (cal.) B.P. The vast majority of all Middle Paleolithic sites in Germany belong to the MMO-B which was, in Southern Germany, rapidly followed by the Upper Paleolithic Aurignacian from 42 ka (cal.) B.P. onwards without any Proto-Aurignacian interlude. © 2016 The Author.


Klevtsov S.,University of Cologne | Wiegmann P.,University of Chicago
Physical Review Letters | Year: 2015

We argue that in addition to the Hall conductance and the nondissipative component of the viscous tensor, there exists a third independent transport coefficient, which is precisely quantized. It takes constant values along quantum Hall plateaus. We show that the new coefficient is the Chern number of a vector bundle over moduli space of surfaces of genus 2 or higher and therefore cannot change continuously along the plateau. As such, it does not transpire on a sphere or a torus. In the linear response theory, this coefficient determines intensive forces exerted on electronic fluid by adiabatic deformations of geometry and represents the effect of the gravitational anomaly. We also present the method of computing the transport coefficients for quantum Hall states. © 2015 American Physical Society. © 2015 American Physical Society.


Friedrich J.,University of Cologne
Journal of Chemical Theory and Computation | Year: 2010

A modified version of the Boys localization method is proposed in order to make the domain-specific basis set approach in the framework of the incremental scheme (J. Chem. Phys. 2008, 129, 244105) generally applicable. The method optimizes the molecular orbitals in one atomic orbital basis set to be similar to localized molecular orbitals in a second atomic orbital basis set under the constraint that the molecular orbitals stay orthonormal. The procedure is tested for RI-MP2 incremental correlation energy expansions for aromatic systems like naphthalene, anthracene, and tetracene as well as for conjugated hydrocarbon chains like C 20H 2, C 20H 22, or p-quaterphenyle. For all investigated systems, a rapid convergence of the incrementally expanded correlation energies to the exact RI-MP2 energies is found. Furthermore, the systematic improvability of the approach is demonstrated. © 2010 American Chemical Society.


Verhoef P.C.,University of Groningen | Reinartz W.J.,University of Cologne | Krafft M.,University of Munster
Journal of Service Research | Year: 2010

Since 2000, customer management (CM) research has evolved and has had a significant impact on the marketing discipline. In an increasingly networked society where customers can interact easily with other customers and firms through social networks and other new media, the authors propose that customer engagement is an important new development in CM. Customer engagement is considered as a behavioral manifestation toward the brand or firm that goes beyond transactions. The authors propose a conceptual model of the antecedents, impediments, and firm consequences of customer engagement and relate this model to seven articles appearing in the special issue on customer engagement. © The Author(s) 2010.


Chraibi M.,Julich Research Center | Seyfried A.,Julich Research Center | Schadschneider A.,University of Cologne
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

A spatially continuous force-based model for simulating pedestrian dynamics is introduced which includes an elliptical volume exclusion of pedestrians. We discuss the phenomena of oscillations and overlapping which occur for certain choices of the forces. The main intention of this work is the quantitative description of pedestrian movement in several geometries. Measurements of the fundamental diagram in narrow and wide corridors are performed. The results of the proposed model show good agreement with empirical data obtained in controlled experiments. © 2010 The American Physical Society.


Kramer R.,University of Cologne
Chemical Record | Year: 2010

When exposed to osmotic stress from the environment, bacteria act to maintain cell turgor and hydration by responding both on the level of gene transcription and protein activity. Upon a sudden decrease in external osmolality, internal solutes are released by the action of membrane embedded mechanosensitive channels. In response to an osmotic upshift, the concentration of osmolytes in the cytoplasm is increased both by de novo synthesis and by active uptake. In order to coordinate these processes of osmoregulation, cells are equipped with systems and mechanisms of sensing physical stimuli correlated to changes in the external osmolality (osmosensing), with pathways to transduce these stimuli into useful signals which can be processed in the cell (signal transduction), and mechanisms of regulating proper responses in the cell to recover from the environmental stress and to maintain all necessary physiological functions (osmoregulation). These processes will be described by a number of representative examples, mainly of osmoreactive transport systems with a focus on available data of their molecular mechanism. © 2010 The Japan Chemical Journal Forum and Wiley Periodicals, Inc.


Ebers M.,University of Cologne | Maurer I.,University of Gottingen
Research Policy | Year: 2014

While research has produced ample evidence showing that absorptive capacity affects innovation and organizational performance outcomes, we still know little about why some organizations possess greater absorptive capacity than others. This study extends previous research by showing how absorptive capacity emerges as an unintended consequence from organizational boundary spanners' external and internal relational embeddedness and their relational empowerment. Drawing upon survey data from 218 inter-organizational projects in the German engineering industry, we propose and find empirically that potential and realized absorptive capacity have partially distinct antecedents. Moreover, we show that the two components of absorptive capacity unfold not only separate but also complementary effects on innovation, implying that the whole of absorptive capacity is greater than its parts. In examining how different components of absorptive capacity emerge and unfold their effects, this study addresses critical limitations of the literature on absorptive capacity. © 2013 Elsevier B.V. All rights reserved.


Langklotz S.,Ruhr University Bochum | Baumann U.,University of Cologne | Narberhaus F.,Ruhr University Bochum
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2012

Proteolysis of regulatory proteins or key enzymes of biosynthetic pathways is a universal mechanism to rapidly adjust the cellular proteome to particular environmental needs. Among the five energy-dependent AAA + proteases in Escherichia coli, FtsH is the only essential protease. Moreover, FtsH is unique owing to its anchoring to the inner membrane. This review describes the structural and functional properties of FtsH. With regard to its role in cellular quality control and regulatory circuits, cytoplasmic and membrane substrates of the FtsH protease are depicted and mechanisms of FtsH-dependent proteolysis are discussed. This article is part of a Special Issue entitled: AAA ATPases: structure and function. © 2011 Elsevier B.V.


Ritter L.,University of Cologne
The International journal of oral & maxillofacial implants | Year: 2012

Implant placement in the edentulous anterior mandible is frequently performed to stabilize prosthetic superstructures. The position of the inferior alveolar nerve (IAN), especially in an atrophic mandible, has to be considered to position implants properly. In this study, the prevalence of looping of the IAN was retrospectively determined to assess the need for imaging prior to implant placement in the anterior mandible. Cone beam computed tomography scans of consecutive patients were evaluated to assess the prevalence and size of IAN looping. The results were compared with respect to patient age and sex as well as degree of atrophy and bone height at the mental foramen. Scans of 1,010 patients were obtained. IAN loops were found in 31% of the patients, with a significantly higher prevalence in male patients (33.1%) than in female patients (28.1%). The average size of loops was 1.4 ± 0.70 mm, with a maximum of 4.6 mm. For male patients, the average loop size was 1.6 ± 0.74 mm (maximum 4.6 mm), and for female patients an average dimension of 1.4 ± 0.63 mm (maximum 4.4 mm) was recorded. This difference was significant (t test). A significant difference with respect to the various classes of atrophy up to class 4 was not found. Loops of the IAN occur in about one third of patients and vary in size from 0.7 to 4.6 mm. Large anterior loops put the IAN at risk when interforaminal implants are placed. Either a sufficient safety distance or three-dimensional imaging procedures should be used to detect loops and locate the incisive canal, which could be harmed during the interforaminal implant placement.


Hoffler F.,University of Cologne | Kranz S.,University of Bonn
International Journal of Industrial Organization | Year: 2011

We study an industry in which an upstream monopolist supplies an essential input at a regulated price to several downstream firms. Legal unbundling means in our model that a downstream firm owns the upstream firm, but this upstream firm is legally independent and maximizes its own upstream profits. We allow for non-tariff discrimination by the upstream firm and show that under quite general conditions legal unbundling never yields lower quantities in the downstream market than ownership separation and integration. Therefore, typically, consumer surplus will be largest under legal unbundling. Outcomes under legal unbundling are still advantageous when we allow for discriminatory capacity investments, investments into marginal cost reduction and investments into network reliability. If access prices are unregulated, however, legal unbundling may be quite undesirable. © 2011 Elsevier B.V. All rights reserved.


Popovych O.V.,Julich Research Center | Tass P.A.,Julich Research Center | Tass P.A.,University of Cologne
Physical Review E - Statistical, Nonlinear, and Soft Matter Physics | Year: 2010

We propose a method for the control of synchronization in two oscillator populations interacting according to a drive-response coupling scheme. The response ensemble of oscillators, which gets synchronized because of a strong forcing by the intrinsically synchronized driving ensemble, is controlled by mixed nonlinear delayed feedback. The stimulation signal is constructed from the mixed macroscopic activities of both ensembles. We show that the suggested method can effectively decouple the interacting ensembles from each other, where the natural desynchronous dynamics can be recovered in a demand-controlled way either in the stimulated ensemble, or, intriguingly, in both stimulated and not stimulated populations. We discuss possible therapeutic applications in the context of the control of abnormal brain synchrony in loops of affected neuronal populations. © 2010 The American Physical Society.


Becks L.,University of Toronto | Becks L.,University of Cologne | Becks L.,Max Planck Institute for Evolutionary Biology | Agrawal A.F.,University of Toronto
PLoS Biology | Year: 2012

Both theory and experiments have demonstrated that sex can facilitate adaptation, potentially yielding a group-level advantage to sex. However, it is unclear whether this process can help solve the more difficult problem of the maintenance of sex within populations. Using experimental populations of the facultatively sexual rotifer Brachionus calyciflorus, we show that rates of sex evolve to higher levels during adaptation but then decline as fitness plateaus. To assess the fitness consequences of genetic mixing, we directly compare the fitnesses of sexually and asexually derived genotypes that naturally occur in our experimental populations. Sexually derived genotypes are more fit than asexually derived genotypes when adaptive pressures are strong, but this pattern reverses as the pace of adaptation slows, matching the pattern of evolutionary change in the rate of sex. These fitness assays test the net effect of sex but cannot be used to disentangle whether selection on sex arises because highly sexual lineages become associated with different allele combinations or with different allele frequencies than less sexual lineages (i.e., "short-" or "long-term" effects, respectively). We infer which of these mechanisms provides an advantage to sex by performing additional manipulations to obtain fitness distributions of sexual and asexual progeny arrays from unbiased parents (rather than from naturally occurring, and thereby evolutionarily biased, parents). We find evidence that sex breaks down adaptive gene combinations, resulting in lower average fitness of sexual progeny (i.e., a short-term disadvantage to sex). As predicted by theory, the advantage to sex arises because sexually derived progeny are more variable in fitness, allowing for faster adaptation. This "long-term advantage" builds over multiple generations, eventually resulting in higher fitness of sexual types. © 2012 Becks, Agrawal.


Kueger S.,University of Cologne | Steinhauser D.,Max Planck Institute of Molecular Plant Physiology | Willmitzer L.,Max Planck Institute of Molecular Plant Physiology | Giavalisco P.,Max Planck Institute of Molecular Plant Physiology
Plant Journal | Year: 2012

The main goal of metabolomics is the comprehensive qualitative and quantitative analysis of the time- and space-resolved distribution of all metabolites present in a given biological system. Because metabolite structures, in contrast to transcript and protein sequences, are not directly deducible from the genomic DNA sequence, the massive increase in genomic information is only indirectly of use to metabolomics, leaving compound annotation as a key problem to be solved by the available analytical techniques. Furthermore, as metabolites vary widely in both concentration and chemical behavior, there is no single analytical procedure allowing the unbiased and comprehensive structural elucidation and determination of all metabolites present in a given biological system. In this review the different approaches for targeted and non-targeted metabolomics analysis will be described with special emphasis on mass spectrometry-based techniques. Particular attention is given to approaches which can be employed for the annotation of unknown compounds. In the second part, the different experimental approaches aimed at tissue-specific or subcellular analysis of metabolites are discussed including a range of non-mass spectrometry based technologies. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.


Alternative splicing of the caldesmon gene results in high (h-caldesmon) and low (l-caldesmon) molecular weight isoforms of the cytoskeleton-associated protein caldesmon. h-Caldesmon is predominantly expressed not only in smooth-muscle cells but also in pericryptal fibroblasts in colon. l-Caldesmon is widely expressed and localized in podosomes/invadopodia. Studies with transformed and cancer cell lines suggest that a reduction in l-caldesmon facilitates podosome/invadopodia formation and metastasis. We investigated caldesmon isoforms in colon adenocarcinoma and their lymph node metastases using immunohistochemistry. Caldesmon immunoreactivity of colon adenocarcinoma primary tumors and lymph node metastases was very similar. l-Caldesmon immunoreactivity of cancer epithelial cells in primary tumors and lymph node metastases varied ranging from reduced to stronger as compared to immunoreactivity of normal areas. The variation did not show a consistent relation to the tumor center or invasive margin. While h-caldesmon immunoreactivity of pericryptal fibroblasts and blood vessels in the stroma of primary tumors and lymph node metastases was markedly reduced, cancer-associated fibroblasts and blood vessels in the stroma were strongly immunoreactive for l-caldesmon. Our results show a differential behavior of h- and l-caldesmon isoforms in epithelium and stroma of colon adenocarcinoma and lymph node metastases. © 2011 Springer-Verlag.


Giernoth R.,University of Cologne
Angewandte Chemie - International Edition | Year: 2010

Melting without heat: Attempts to design new ionic liquids (often functionalized) often lead to only "ionic solids". Two recent studies demonstrate very promising and viable ways to "liquify" systems that are based on the common structural motifs that still dominate the literature (see picture; Tf2N-= bis(trifluoromethylsulfonyl)imide. © 2010 Wiley-VCH Verlag GmbH & Co. KCaA, Weinheim.


Ellenbroek S.I.J.,Netherlands Cancer Institute | Ellenbroek S.I.J.,University Utrecht | Iden S.,Netherlands Cancer Institute | Iden S.,University of Cologne | Collard J.G.,Netherlands Cancer Institute
Seminars in Cancer Biology | Year: 2012

Cell polarity is essential in many biological processes and required for development as well as maintenance of tissue integrity. Loss of polarity is considered both a hallmark and precondition for human cancer. Three conserved polarity protein complexes regulate different modes of polarity that are conserved throughout numerous cell types and species. These complexes are the Crumbs, Par and Scribble complex. Given the importance of cell polarity for normal tissue homeostasis, aberrant polarity signaling is suggested to contribute to the multistep processes of human cancer. Most human cancers are formed from epithelial cells. Evidence confirming the roles for polarity proteins in different phases of the oncogenic trajectory comes from functional studies using mammalian cells as well as Drosophila and zebrafish models. Furthermore, several reports have revealed aberrant expression and localization of polarity proteins in different human tumors. In this review we will give an overview on the current data available that couple polarity signaling to tumorigenesis, particularly in epithelial cells. © 2012 Elsevier Ltd.


Helmes J.,RWTH Aachen | Helmes J.,University of Cologne | Wessel S.,RWTH Aachen
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

We examine the entanglement properties of the spin-half Heisenberg model on the two-dimensional square-lattice bilayer based on quantum Monte Carlo calculations of the second Rényi entanglement entropy. In particular, we extract the dominant area-law contribution to the bipartite entanglement entropy that shows a nonmonotonous behavior upon increasing the interlayer exchange interaction: a local maximum in the area-law coefficient is located at the quantum critical point separating the antiferromagnetically ordered region from the disordered dimer-singlet regime. Furthermore, we consider subleading logarithmic corrections to the Rényi entanglement entropy scaling. Employing different subregion shapes, we isolate the logarithmic corner term from the logarithmic contribution due to Goldstone modes that is found to be enhanced in the limit of decoupled layers. At the quantum critical point, we estimate a contribution of 0.016(1) due to each 90 corner. This corner term at the SU(2) quantum critical point deviates from the Gaussian theory value, while it compares well with recent numerical linked cluster calculations on the bilayer model. © 2014 American Physical Society.


Held P.,University of Cologne
Acta Crystallographica Section E: Structure Reports Online | Year: 2014

In the title salt, [(CH3)2NH2][Cu(HSO 4)(SO4)(H2O)4], one type of cation and anion is present in the asymmetric unit. The CuII atom in the complex anion, [Cu(HSO4)(SO4)(H2O)4] -, has a tetragonal bipyramidal [4 + 2] coordination caused by a Jahn-Teller distortion, with the aqua ligands in equatorial and two O atoms of tetrahedral HSO4 and SO4 units in apical positions. Both types of ions form sheets parallel to (010). The interconnection within and between the sheets is reinforced by O-H..O and N-H..O hydrogen bonds, respectively, involving the water molecules, the two types of sulfate anions and the ammonium groups.


Held P.,University of Cologne
Acta Crystallographica Section E: Structure Reports Online | Year: 2014

In the title molecular salt, [NH2(CH2CH3)2][H2PO4], two unique types of cations and anions, which are configurationally very similar, are present in the asymmetric unit. Both ions form sheets approximately parallel to (-1-1) linked by weak hydrogen bonds. The interconnection within and between the sheets is reinforced by O - HO and N - HO hydrogen bonds involving the tetrahedral H2PO4 anions and the ammonium groups. © Peter Held 2014.


Grefkes C.,University of Cologne | Grefkes C.,Max Planck Institute for Neurological Research | Ward N.S.,University College London
Neuroscientist | Year: 2014

The brain has an intrinsic capacity to compensate for structural damage through reorganizing of surviving networks. These processes are fundamental for recovery of function after many forms of brain injury, including stroke. Functional neuroimaging techniques have allowed the investigation of these processes in vivo. Here, we review key advances over the past two decades that have shed light on the neural mechanisms enabling recovery of motor function after stroke. We first provide an overview on invasive stroke models in non-human primates that provided insights into lesion-induced changes in the cortical representations of the upper limb. We then present key findings from neuroimaging studies in human stroke patients, which suggest that the role of contralesional motor hemisphere in supporting recovered function depends on factors such as time since stroke, lesion location and anatomical region. More recently, research has been directed at understanding how surviving brain regions influence one another during movement. It appears that it is not only the corticospinal tract but also brainstem pathways and interhemispheric connections that affect cortical reorganization patterns and functional recovery. In summary, neuroimaging opens the way for greater understanding of the mechanisms of recovery and potentially improves our ability to deliver effective restorative therapy. © The Author(s) 2013.


Wongso D.,University of Cologne
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated). In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.


Bercioux D.,Albert Ludwigs University of Freiburg | De Martino A.,University of Cologne
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

We address the problem of spin-resolved scattering through spin-orbit nanostructures in graphene, i.e., regions of inhomogeneous spin-orbit coupling on the nanometer scale. We discuss the phenomenon of spin-double refraction and its consequences on the spin polarization. Specifically, we study the transmission properties of a single and a double interface between a normal region and a region with finite spin-orbit coupling, and analyze the polarization properties of these systems. Moreover, for the case of a single interface, we determine the spectrum of edge states localized at the boundary between the two regions and study their properties. © 2010 The American Physical Society.


Wu H.,University of Cologne
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

Spin state is an important issue for many cobaltates, and an intermediate spin (IS) state having a half-filled eg orbital may well be expected for a Co3+ ion in a CoO6 octahedron with a remarkable tetragonal distortion. Here the single-layered perovskite cobaltate LaSrCoO4, which has a notable tetragonal elongation, is investigated for its spin state and electronic structure, through a set of local-spin-density approximation plus Hubbard U (LSDA+U) calculations including also the multiplet effect and spin-orbit coupling. Counterintuitively, our calculations evidence that the IS state is not the ground state and it would, even if being so, give rise to a wrong ferromagnetic half-metallic solution. We find that a strong band hybridization significantly suppresses a multiplet energy splitting of the IS state. Instead, a high-spin (HS) and low-spin (LS) mixed state turns out to have the lowest total energy among all possibly combined spin states. Moreover, the mixed HS+LS ground state well accounts for the experimental paramagnetic insulating behavior, the effective magnetic moment, and the observed optical spectral features. We also predict that LaSrCoO4 in the mixed HS+LS ground state has a sizeable out-of-plane orbital moment and a local lattice distortion, which would motivate experimental studies. © 2010 The American Physical Society.


Khomskii D.I.,University of Cologne
Journal of Physics Condensed Matter | Year: 2010

The standard point of view is that at low energies Mott insulators exhibit only magnetic properties, while charge degrees of freedom are frozen out because electrons are localized. We demonstrate (Bulaevskii et al 2008 Phys. Rev. B 78 024402) that in general this is not true: for certain spin textures there exist quite nontrivial charge effects in the ground and lowest excited states. We show that in frustrated systems spontaneous orbital currents may exist in the ground state, proportional to the scalar spin chirality. For other spin structures spontaneous charge redistribution may exist, so that the average charge at a site is different from 1. This can lead to the appearance of dipole moments and possibly of the net spontaneous polarization. This is a novel, purely electronic mechanism of multiferroic behaviour. We also discuss some dynamic consequences, such as dipole-active 'ESR' transitions. Also, the possibility of using chirality instead of spin in memory applications is briefly discussed. © 2010 IOP Publishing Ltd.


Cornely O.A.,University of Cologne
Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2013

Patients with cancer are at increased risk for Clostridium difficile-associated diarrhea (CDAD). Little is known about treatment response. Two double-blind trials randomly allocated 1,105 patients with CDAD to fidaxomicin or vancomycin treatment (modified intent-to-treat [mITT]), and 183 of these had cancer. Univariate and multivariate post hoc analyses compared effects of treatment and patient characteristics on cure, recurrence, and sustained response after 4 weeks. Time to resolution of diarrhea (TTROD) was also evaluated. Patients with cancer had a lower cure rate and longer TTROD than patients without cancer. Recurrence rates were similar. Cure was more likely with fidaxomicin than vancomycin (odds ratio [OR] 2.0; P = .065), recurrence was less likely (OR = 0.37; P = .018), and sustained response more frequent (OR = 2.56; P = .003). Under vancomycin, median TTROD was longer in patients with cancer than in those without (123 v 58 hours; log-rank P < .001). With fidaxomicin, median TTROD was not significantly affected by presence of cancer (74 v 54 hours; log-rank P = .145). In the full mITT population, age, hypoalbuminemia, and cancer were inversely associated with clinical cure by multivariate analysis. Study treatment with vancomycin was a significant predictor of recurrence (P < .001). Within the cancer population, low albumin was negatively and fidaxomicin was positively associated with improved cure. For patients with cancer, fidaxomicin treatment was superior to vancomycin, resulting in higher cure and sustained response rates, shorter TTROD, and fewer recurrences.


Schwarz G.,University of Cologne
Current Opinion in Chemical Biology | Year: 2016

Four molybdenum-dependent enzymes are known in humans, each harboring a pterin-based molybdenum cofactor (Moco) in the active site. They catalyze redox reactions using water as oxygen acceptor or donator. Moco is synthesized by a conserved biosynthetic pathway. Moco deficiency results in a severe inborn error of metabolism causing often early childhood death. Disease-causing symptoms mainly go back to the lack of sulfite oxidase (SO) activity, an enzyme in cysteine catabolism. Besides their name-giving functions, Mo-enzymes have been recognized to catalyze novel reactions, including the reduction of nitrite to nitric oxide. In this review we cover the biosynthesis of Moco, key features of Moco-enzymes and focus on their deficiency. Underlying disease mechanisms as well as treatment options will be discussed. © 2016 Published by Elsevier Ltd.


Gassner G.J.,University of Cologne
International Journal for Numerical Methods in Fluids | Year: 2014

In this work, we discuss the construction of a skew-symmetric discontinuous Galerkin (DG) collocation spectral element approximation for the compressible Euler equations. Starting from the skew-symmetric formulation of Morinishi, we mimic the continuous derivations on a discrete level to find a formulation for the conserved variables. In contrast to finite difference methods, DG formulations naturally have inter-domain surface flux contributions due to the discontinuous nature of the approximation space. Thus, throughout the derivations we accurately track the influence of the surface fluxes to arrive at a consistent formulation also for the surface terms. The resulting novel skew-symmetric method differs from the standard DG scheme by additional volume terms. Those volume terms have a special structure and basically represent the discretization error of the different product rules. We use the summation-by-parts (SBP) property of the Gauss-Lobatto-based DG operator and show that the novel formulation is exactly conservative for the mass, momentum, and energy. Finally, an analysis of the kinetic energy balance of the standard DG discretization shows that because of aliasing errors, a nonzero transport source term in the evolution of the discrete kinetic energy mean value may lead to an inconsistent increase or decrease in contrast to the skew-symmetric formulation. Furthermore, we derive a suitable interface flux that guarantees kinetic energy preservation in combination with the skew-symmetric DG formulation. As all derivations require only the SBP property of the Gauss-Lobatto-based DG collocation spectral element method operator and that the mass matrix is diagonal, all results for the surface terms can be directly applied in the context of multi-domain diagonal norm SBP finite difference methods. Numerical experiments are conducted to demonstrate the theoretical findings. © 2014 John Wiley & Sons, Ltd.


Zenz T.,German Cancer Research Center | Zenz T.,University of Heidelberg | Gribben J.G.,Queen Mary, University of London | Hallek M.,University of Cologne | And 3 more authors.
Blood | Year: 2012

Standardized criteria for diagnosis and response evaluation in chronic lymphocytic leukemia (CLL) are essential to achieve comparability of results and improvement of clinical care. With the increasing range of therapeutic options, the treatment context is important when defining refractory CLL. Refractory CLL has been defined as no response or response lasting > 6 months from last therapy. This subgroup has a very poor outcome, and many trials use this group as an entry point for early drug development. With the intensification of first-line regimens, the proportion of patients with refractory CLL using these criteria decreases. This has immediate consequences for recruitment of patients into trials as well as salvage strategies. Conversely, patients who are not refractory according to the traditional definition but who have suboptimal or short response to intense therapy also have a very poor outcome. In this Perspective, we discuss recent results that may lead to a reassessment of risk categories in CLL focusing on fit patients who are eligible for all treatment options. We cover aspects of the history and biologic basis for refractory CLL and will focus on how emerging data on treatment failure from large trials using chemoimmunotherapy may help to define risk groups in CLL. © 2012 by The American Society of Hematology.


Quasdorff M.,University of Cologne | Protzer U.,TU Munich
Journal of Viral Hepatitis | Year: 2010

Hepatitis B virus (HBV) is tightly controlled by a number of noncytotoxic mechanisms. This control occurs within the host hepatocyte at different steps of the HBV replication cycle. HBV persists by establishing a nuclear minichromosome, HBV cccDNA, serving as a transcription template for the viral pregenome and viral mRNAs. Nucleoside/nucleotide analogues widely used for antiviral therapy as well as most antiviral cytokines act at steps after transcription of HBV RNAs and thus can control virus replication but do not directly affect its gene expression. Control of HBV at the level of transcription in contrast is able to restrict both, HBV replication and gene expression. In the review, we focus on how HBV is controlled at the level of transcription. We discuss how the composition of transcription factors determines HBV gene expression and replication and how this may be influenced by antivirally active substances, e.g. the cytokine IL-6 or helioxanthin analogues, or by the differentiation state of the hepatocyte. © 2010 Blackwell Publishing Ltd.


Mitra A.,New York University | Rosch A.,University of Cologne
Physical Review Letters | Year: 2011

The properties of a local spin S=1/2 coupled to K independent wires is studied in the presence of bias voltages which drive the system out of thermal equilibrium. For K≫1, a perturbative renormalization group approach is employed to construct the voltage-dependent scaling function for the conductance and the T matrix. In contrast to the single-channel case, the Kondo resonance is split even by bias voltages small compared to the Kondo temperature T K, V≪T K. Besides the applied voltage V, the current-induced decoherence rate Γ≪V controls the physical properties of the system. While the presence of V changes the structure of the renormalization group considerably, decoherence turns out to be very effective in prohibiting the flow towards new nonequilibrium fixed points even in variants of the Kondo model where currents are partially suppressed. © 2011 American Physical Society.


Sastre J.,Autonomous University of Madrid | Sastre J.,CIBER ISCIII | Mosges R.,University of Cologne
Journal of Investigational Allergology and Clinical Immunology | Year: 2012

The safety and efficacy of intranasal corticosteroids (INCs) are well established for the management of allergic rhinitis, rhinosinusitis, and nasal polyps. As seen in numerous studies, INCs demonstrate markedly reduced systemic bioavailability compared with oral and even inhaled corticosteroids and have shown an excellent safety profile over 3 decades of use. Nonetheless, concerns remain among some prescribers and patients that these agents may reach the systemic circulation in sufficient concentration to produce adverse effects (AEs). Available evidence does not support these concerns. A review of the published literature indicates that the side effect profiles of INCs consist primarily of a low incidence of mostly mild and often transient local AEs, such as nasal irritation and epistaxis. The second-generation INC agents currently in use (mometasone furoate nasal spray, fluticasone propionate, ciclesonide, and fluticasone furoate) have favorable pharmacokinetic characteristics that further minimize systemic bioavailability (<1%) compared with older INCs and compared with oral agents, thereby limiting the risk for systemic adverse events. © 2012 Esmon Publicidad.


Choi Y.,Centers for Disease Control and Prevention | Dienes H.-P.,University of Cologne | Krawczynski K.,Centers for Disease Control and Prevention
PLoS ONE | Year: 2013

The relationships among micro RNA-122 (miR-122) expression in the liver, hepatitis C virus (HCV) replication and hepatic damage were analyzed in three chimpanzees observed for 180 days after inoculation with HCV genotype 1a. Levels of miR-122 in the liver and serum were measured by real-time RT PCR in serial liver biopsies and serum samples. Hepatic miR-122 levels were normalized separately for each of three chimpanzees with small RNAs and microRNAs that are endogenous to the liver and are stably expressed. Two- to 4-fold rise in hepatic miR-122 levels was observed at the onset of HCV infection (the first 4 weeks) when HCV titers in the liver and serum increased rapidly in all three chimpanzees in concordance with in vitro data indicating the miR-122 significance for HCV replication. Between 10 to 14 weeks after inoculation, when hepatic and serum HCV RNA titers exceeded 3 logs and alanine aminotransferase (ALT) activity was elevated, hepatic miR-122 levels were in decline. Cumulative data derived from all three chimpanzees from 180 days of observation documented an inverse (negative) correlation between hepatic miR-122 and HCV RNA in the liver and serum and positive correlation between level of serum miR-122 and HCV replication. Subsequent rise of miR-122 level during HCV clearance and ALT normalization suggested a tri-phasic occurrence of the relationship among hepatic miR-122 expression, HCV replication and hepatic destruction, which was the most apparent in one chimpanzee but less evident in two other animals. In vivo kinetics of hepatic and serum miR-122, HCV replication and hepatic destruction reflects complexities of the virus-host interaction during the acute phase of HCV infection.


Greiner C.,University of Cologne
Human Ecology | Year: 2012

This article is concerned with the implementation of community-based conservancies (CBC) in conflict-ridden pastoralist areas of northern Kenya and whether the creation of protected areas can facilitate the resolution of conflict. Evidence from ethnographic research in East Pokot, Kenya, reveals a mixed picture. In the last decade, three CBCs were established along the administrative borders. Two of them are located in contested areas between the Pokot and neighboring pastoralists. In order to ensure their long-term success in terms of wildlife conservation and economic viability they must act as catalysts for inter-ethnic conflict resolution. In one case, the implementation proved successful, while in the other it exacerbated tensions and led to ethnic violence. In addition, issues of conservation are also embedded in deeper intra-societal struggles over the reconfiguration and renegotiation of access to and control over land. Drawing on ethnographic data and recent literature this research sheds light on unexpected consequences of CBC. © 2012 Springer Science+Business Media, LLC.


In this article, the flexibility of the German power market with respect to the integration of an increasing share of electricity from renewable energy sources was analysed. Flexibility limiting system components, which cause negative prices, are explained and illustrated for the German market. The decision of the European Energy Exchange in Leipzig to allow negative price bids is then explained. The empirical data illustrate the flexibility of conventional generating capacities in Germany from October 2008 to December 2009. Of the 86. h of negative spot prices, 19. h were significantly negative, with prices of at least -100. €/MWh. These extreme hours were analysed in greater detail by the examination of different system components. Thereby, load, wind power infeed and conventional generation by fuel type were observed, as well as the market for negative tertiary reserve, as indicators for market tightness. Although the market situations were found to be severe, under the current conditions, it could have been much worse. In order to enable the market to clear at all times, policy recommendations are provided and long-run implications of an increasing RES-E share on the conventional generation capacity are discussed. The article concludes with an outlook on additional power system flexibility options. © 2010 Elsevier Ltd.


Dolg M.,University of Cologne
Journal of Chemical Theory and Computation | Year: 2011

Segmented contracted scalar-relativistic (23s16p12d6f)/[18s12p9d3f] all-electron basis sets for lanthanides La-Lu primarily for use in second-order Douglas-Kroll-Hess density functional calculations are presented. Atomic test calculations at the scalar-relativistic Hartree-Fock level reveal an accurate description of the first to fourth ionization potentials as well as low-energy d-f and d-p excitation energies; i.e., reference data obtained with optimized (34s28p22d16f) even-tempered basis sets are reproduced with mean absolute errors of 0.003 (IP1), 0.013 (IP2), 0.030 (IP3), 0.098 (IP4), 0.070 (d-f), and 0.018 (d-p) eV. Results of molecular test calculations are presented for the lanthanide trihalides LnX3 (Ln = La-Lu, X = F, Cl, Br, I) at the PBE0 hybrid density functional theory level. Compared to recently published basis sets of identical size, the sets proposed here show substantially smaller errors in the atomic test calculations as well as lower total energies and produce results of similar accuracy in the molecular calibration study. © 2011 American Chemical Society.


Reticular cells and follicular dendritic cells (FDCs) build up a framework that underlies the compartmentalization of spleens and lymph nodes. Subpopulations of reticular cells express the smooth-muscle isoform of actin, indicative of a specialized contractile apparatus. We have investigated the distribution of the actin-binding protein caldesmon in spleen and lymph nodes of mice and rats. Caldesmon modulates contraction and regulates cell motility. Alternative splicing of transcripts from a single gene results in high-molecular-mass isoforms (h-caldesmon) that are predominately expressed by smooth-muscle cells (SMCs), and low-molecular-mass isoforms (l-caldesmon) that are thought to be widely distributed in non-muscle tissues, but the distribution of caldesmon in spleen and lymph nodes has not been reported. We have performed Western blot analysis and immunohistochemistry using four different antibodies against caldesmon, among these a newly developed polyclonal antibody directed against recombinant mouse caldesmon. Western blot analysis showed the preponderance of l-caldesmon in spleen and lymph nodes. Our results from immunohistochemistry demonstrate caldesmon in SMCs, as expected, but also in reticular cells and FDCs, and suggest that the isoform highly expressed by reticular cells is l-caldesmon. In spleen of SCID mice, caldesmon was expressed by reticular cells in the absence of lymphocytes. © 2010 Köhler.


Pfister D.,University of Cologne
Current Opinion in Urology | Year: 2016

PURPOSE OF REVIEW: In testis cancer, prognosis is excellent even in metastatic disease. Treatment and timing of patients with multiple metastatic deposits can be challenging. This review was performed to underline the current guideline recommendations. RECENT FINDINGS: Depending on the primary histology, the indication of further surgical resections differ. In seminoma, resídual tumor resections are performed according to the results of a flouoro-deoxy-D-glucose-PET. Positive results must be considered critically, and to recent results it is advisable to first repeat flouoro-deoxy-D-glucose-PET to avoid overtreatment. In nonseminomatous germ cell cancer, complete remissions in good prognosis patients are followed and can be spared from surgery. All other patients still need to undergo postchemotherapy retroperitoneal lymph node dissection. In bone metastases, significant histology is found in 80% so that one should go for complete resection. In liver metastases, resections can be performed according to the histology in the retroperitoneum. Both resections, including vessel replacement, are usually performed in one session underlining the complex multidisciplinary approach. Pulmonal metastases, at least in one lobe, need to be resected. Brain metastases are rare with no standard treatment recommendation. SUMMARY: Every patient should be presented in a multidisciplinary tumor board. Surgical interventions should be done in tertiary referral centers to achieve the best oncologic outcome and reduced morbidity. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


A novel analytical and continuous density distribution function with a widely variable shape is reported and used to derive an analytical scattering form factor that allows us to universally describe the scattering from particles with the radial density profile of homogeneous spheres, shells, or core-shell particles. Composed by the sum of two Fermi-Dirac distribution functions, the shape of the density profile can be altered continuously from step-like via Gaussian-like or parabolic to asymptotically hyperbolic by varying a single "shape parameter", d. Using this density profile, the scattering form factor can be calculated numerically. An analytical form factor can be derived using an approximate expression for the original Fermi-Dirac distribution function. This approximation is accurate for sufficiently small rescaled shape parameters, d/R (R being the particle radius), up to values of d/R ≈ 0.1, and thus captures step-like, Gaussian-like, and parabolic as well as asymptotically hyperbolic profile shapes. It is expected that this form factor is particularly useful in a model-dependent analysis of small-angle scattering data since the applied continuous and analytical function for the particle density profile can be compared directly with the density profile extracted from the data by model-free approaches like the generalized inverse Fourier transform method. © 2011 American Chemical Society.


Schumacher P.B.,Johannes Gutenberg University Mainz | Baumann S.,University of Cologne
NeuroReport | Year: 2010

Discourse processing depends on semantic memory as well as maintaining and updating of a mental model. Using event-related potentials, we investigated how a referent's information status (new, accessible, given) is processed in combination with three different prosodic realizations (an appropriate accent and two inappropriate accents). The data reveal a biphasic N400-late positivity pattern, indicating that prosodic information affects an early discourse linking stage, during which prominence information reflecting a referent's accessibility is computed (N400), and a later discourse updating stage, during which conflicts between prosodic information and a referent's actual information status are detected (late positivity). Crucially, the data show that the N400 is not only sensitive to lexico-semantic relations but also to discourse accessibility induced by prosodic cues. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Stahl J.,University of Cologne
International Journal of Psychophysiology | Year: 2010

The error-related negativity (Ne/ERN) and the feedback-related negativity (FRN) are electrophysiological markers of error processing, which originate from the medial frontal cortex. A digit-flanker task with a strict individual response time (RT) limit was employed to test the first-indicator hypothesis. This hypothesis postulates an increase in medial frontal brain activity only after the first, internal (response related) or external (feedback related), indicator of an incorrect response. In order to examine whether this hypothesis also holds for RT errors, a simple digit-flanker task was employed. The participants (n=14) committed three error types: a hand error, an RT error, and a combination of hand and RT error (double error). It was assumed that they were able to detect hand errors at the time of responding, whereas reliable RT error detection should require an external feedback. The experimental findings demonstrated that hand errors were followed by an increase in Ne/ERN amplitude, but not in FRN amplitude. RT errors committed marginally beyond the RT limit showed an increase in FRN amplitude but not in Ne/ERN amplitude, whereas RT errors that were far beyond RT limit affected Ne/ERN, but not FRN. The present findings supported the first-indicator hypothesis. Evidence was given of an error detection system, which was sensitive to a violation of an RT limit. © 2010 Elsevier B.V.


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

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


Niemann C.,University of Cologne | Horsley V.,Yale University
Seminars in Cell and Developmental Biology | Year: 2012

The important role of epidermal appendages especially the sebaceous gland has only recently been recognized. In particular, it has been convincingly shown that normal development and maintenance of the sebaceous gland are required for skin homeostasis since atrophic sebaceous glands and disturbances in sebaceous lipid composition result in major defects of the physiological barrier and maintenance of the skin. Consequently, it is important to unravel the signaling network controlling proper sebaceous lineage differentiation in mammalian skin and to understand the underlying mechanisms leading to severe skin diseases, including abnormal proliferation and differentiation of the gland, defects of the lipid metabolism and barrier, as well as sebaceous tumor formation. Over the last years, results from transgenic and knock out mouse models manipulating distinct signaling pathways in the skin as well as the detailed analysis of human sebaceous gland-derived cell lines provided new insights into crucial mediators balancing proliferation and differentiation of the sebaceous gland. Here, we discuss our current knowledge of in vivo mechanisms of sebaceous gland development, maintenance and disorders and highlight recent contributions to the field of sebaceous gland biology. © 2012 Elsevier Ltd.


Chandler J.W.,University of Cologne
Critical Reviews in Plant Sciences | Year: 2014

The initial event in plant floral organogenesis is bract specification, followed by floral meristem (FM) initiation in bract axils, but initiation signals and the interplay between both lateral organs remain unelucidated. Floral organs are initiated on the flanks of the outgrowing FM and the enormous diversity in floral morphology throughout the plant kingdom reflects variations in organ position, meristy and ontogeny. Classical models of floral development have focused on Arabidopsis, which has mostly actinomorphic flowers, and Antirrhinum, which exhibits zygomorphy, although neither species is typical or representative of angiosperm flower diversity. Although the ABCE model defines a centripetal model of organ identity establishment in different whorls, the characterization of floral organ initiation in many species has relied on their morphological appearance, due to a lack of founder cell-specific markers. Recent progress in early Arabidopsis floral development using histology, molecular markers and mutants has led to refinements of existing floral organ initiation paradigms. In Arabidopsis, sepals initiate unidirectionally, in a temporal window characterized by the absence of CLAVATA3 and WUSCHEL stem cell markers and are partly dependent on PRESSED FLOWER function, whereas initiation of inner-whorl organs occurs centripetally. Arabidopsis mutants reveal that the FM is highly polarized along an ab-/adaxial axis and a comparison of floral development in Arabidopsis and Antirrhinum suggests that heterochrony of conserved gene functions has been evolutionarily adaptive.This review discusses current views on FM and organ specification signals, the gene regulatory networks that underlie floral meristem polarity, and analogies between the development of floral and leaf primordia as lateral organs. Alternative stem-cell proliferation mechanisms and the bifurcation of founder cell populations can help to explain the diversity in floral diversity throughout the plant kingdom and underpin comparative evolutionary biology and macroevolution. An analysis of plants with divergent body plans at the level of organ specification is urgently needed. © 2014 Copyright © Taylor & Francis Group, LLC.


Kriecherbauer T.,Ruhr University Bochum | Krug J.,University of Cologne
Journal of Physics A: Mathematical and Theoretical | Year: 2010

These notes are based on lectures delivered by the authors at a Langeoog seminar of SFB/TR12 Symmetries and Universality in Mesoscopic Systems to a mixed audience of mathematicians and theoretical physicists. After a brief outline of the basic physical concepts of equilibrium and nonequilibrium states, the one-dimensional simple exclusion process is introduced as a paradigmatic nonequilibrium interacting particle system. The stationary measure on the ring is derived and the idea of the hydrodynamic limit is sketched. We then introduce the phenomenological Kardar-Parisi-Zhang (KPZ) equation and explain the associated universality conjecture for surface fluctuations in growth models. This is followed by a detailed exposition of a seminal paper of Johansson [59] that relates the current fluctuations of the totally asymmetric simple exclusion process (TASEP) to the Tracy-Widom distribution of random matrix theory. The implications of this result are discussed within the framework of the KPZ conjecture. © 2010 IOP Publishing Ltd.


Schilbach L.,Max Planck Institute of Psychiatry | Schilbach L.,University of Cologne
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2016

Psychiatric disorders can affect our ability to successfully and enjoyably interact with others. Conversely, having difficulties in social relations is known to increase the risk of developing a psychiatric disorder. In this article, the assumption that psychiatric disorders can be construed as disorders of social interaction is reviewed from a clinical point of view. Furthermore, it is argued that a psychiatrically motivated focus on the dynamics of social interaction may help to provide new perspectives for the field of social neuroscience. Such progress may be crucial to realize social neuroscience’s translational potential and to advance the transdiagnostic investigation of the neurobiology of psychiatric disorders. © 2015 The Author(s) Published by the Royal Society. All rights reserved.


Doerfler W.,Friedrich - Alexander - University, Erlangen - Nuremberg | Doerfler W.,University of Cologne
Epigenomics | Year: 2012

The insertion of foreign DNA into mammalian genomes can alter their methylation and transcription patterns at remote sites from the locus of foreign DNA integration. The mechanisms leading to these fundamental changes and their frequencies are unknown. Sites and extent of changes in the recipient cells might depend on the location of foreign DNA integration. In the second part of this review, it will be hypothesized that the insertion event itself, for example, of tumor viral DNA via its epigenetic genome-wide consequences, plays an important role in oncogenesis. During evolution, the impact of ancient retrotransposon or retroviral genomes and the ensuing epigenetic alterations in the recipient genomes might have generated cells with completely different transcriptional profiles. Due to the continued presence of the transgenomes these alterations were genetically stable and were selected for or against by the environmental conditions prevalent at the time. These evolutionary effects are very different from those postulated for insertional mutagenesis, added genetic information or regulatory elements placed into the vicinity of cellular functions. © 2012 Future Medicine Ltd.


Hero B.,University of Cologne | Schleiermacher G.,University Pierre and Marie Curie
Neuropediatrics | Year: 2013

Opsoclonus myoclonus syndrome (dancing eye syndrome) is a rare paraneoplastic syndrome characterized by opsoclonus, myoclonus, and ataxia, usually accompanied by behavioral abnormalities. In adults, opsoclonus myoclonus syndrome has been reported in association with different types of cancer; whereas in children, the syndrome may be associated with neuroblastic tumors. Although a direct proof is lacking, the syndrome is assumed to be of autoimmune origin. The treatment is corticosteroid based with the addition of other immunosuppressive or immunomodulating drugs if intensification seems necessary. Because of the rarity of the disease, international collaborations as well on research as on therapeutic strategies are urgently needed. A European consortium just started a trial for this rare condition. © 2013 Georg Thieme Verlag KG Stuttgart.


Clemen C.S.,University of Cologne | Herrmann H.,German Cancer Research Center | Strelkov S.V.,Catholic University of Leuven | Schroder R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta Neuropathologica | Year: 2013

The intermediate filament protein desmin is an essential component of the extra-sarcomeric cytoskeleton in muscle cells. This three-dimensional filamentous framework exerts central roles in the structural and functional alignment and anchorage of myofibrils, the positioning of cell organelles and signaling events. Mutations of the human desmin gene on chromosome 2q35 cause autosomal dominant, autosomal recessive, and sporadic myopathies and/or cardiomyopathies with marked phenotypic variability. The disease onset ranges from childhood to late adulthood. The clinical course is progressive and no specific treatment is currently available for this severely disabling disease. The muscle pathology is characterized by desmin-positive protein aggregates and degenerative changes of the myofibrillar apparatus. The molecular pathophysiology of desminopathies is a complex, multilevel issue. In addition to direct effects on the formation and maintenance of the extra-sarcomeric intermediate filament network, mutant desmin affects essential protein interactions, cell signaling cascades, mitochondrial functions, and protein quality control mechanisms. This review summarizes the currently available data on the epidemiology, clinical phenotypes, myopathology, and genetics of desminopathies. In addition, this work provides an overview on the expression, filament formation processes, biomechanical properties, post-translational modifications, interaction partners, subcellular localization, and functions of wild-type and mutant desmin as well as desmin-related cell and animal models. © 2012 Springer-Verlag Berlin Heidelberg.


Scheel A.H.,University of Cologne
Modern Pathology | Year: 2016

Immunohistochemistry of the PD-L1 protein may be predictive for anti-PD-1 and anti-PD-L1 immunotherapy in pulmonary adenocarcinoma and in clinically unselected cohorts of so-called non-small-cell lung cancer. Several PD-L1 immunohistochemistry assays with custom reagents and scoring-criteria are developed in parallel. Biomarker testing and clinical decision making would profit from harmonized PD-L1 diagnostics. To assess interobserver concordance and PD-L1 immunohistochemistry staining patterns, 15 pulmonary carcinoma resection specimens (adenocarcinoma: n=11, squamous-cell carcinoma: n=4) were centrally stained with the assays 28-8, 22C3, SP142, and SP263 according to clinical trial protocols. The slides were evaluated independently by nine pathologists. Proportions of PD-L1-positive carcinoma cells and immune cells were scored according to a 6-step system that integrates the criteria employed by the four PD-L1 immunohistochemistry assays. Proportion scoring of PD-L1-positive carcinoma cells showed moderate interobserver concordance coefficients for the 6-step scoring system (Light's kappa=0.47–0.50). The integrated dichotomous proportion cut-offs (≥1, ≥5, ≥10, ≥50%) showed good concordance coefficients (κ=0.6–0.8). Proportion scoring of PD-L1-positive immune cells yielded low interobserver concordance coefficients both for the 6-step-score (κ<0.2) and the dichotomous cut-offs (κ=0.12–0.25). The assays 28-8 and 22C3 stained similar proportions of carcinoma cells in 12 of 15 cases. SP142 stained fewer carcinoma cells compared to 28-8, 22C3, and SP263 in four cases, whereas SP263 stained more carcinoma cells in nine cases. SP142 and SP263 stained immune cells more intensely. The data indicate that carcinoma cells can be reproducibly scored in PD-L1 immunohistochemistry for pulmonary adenocarcinoma and squamous-cell carcinoma. No differences in interobserver concordance were noticed among the tested assays. The scoring of immune cells yielded low concordance rates and might require specific standardization. The four tested PD-L1 assays did not show comparable staining patterns in all cases. Thus, studies that correlate staining patterns and response to immunotherapy are required to test the significance of the observed differences.Modern Pathology advance online publication, 8 July 2016; doi:10.1038/modpathol.2016.117. © 2016 United States & Canadian Academy of Pathology


Meyer G.,University of Cologne
Angewandte Chemie - International Edition | Year: 2010

(Figure Presented) From SIR to BIR: Following the concept of the sterically induced reduction (SIR), the base-induced reaction (BIR) has now been discovered. [Sm(AlMe4)3] reacts with the bulky base 1,3,5-tricyclohexyl-1,3,5-triazacyclohexane (TCyTAC) in benzene to give [(TCyTAC)2SmII(AlMe4)2] (see picture; Sm red, Al dark gray, N green, C light gray) and ethane, and is in competition with C - H activation yielding [TCyTAC)2Sm{CH(AlMe 3)3}] and methane. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Neggers R.A.J.,University of Cologne
Journal of Advances in Modeling Earth Systems | Year: 2015

This study explores a mass flux framework for moist convective transport and clouds that is formulated in terms of discretized size densities. The properties of each bin in these histograms are estimated individually, making use of a rising plume model. In this framework, the number density acts as a weight, appearing in the area fraction of the mass flux. Such "bin-macrophysics" models have the benefit that bulk closures become redundant, and that scale-awareness is introduced at the basis of the formulation. Large-eddy simulation results are used to verify the design of this framework and to constrain associated constants of proportionality. The behavior of the framework is explored by means of single-column model simulations of various idealized cases of shallow and deeper surface-driven convection. A smoothly developing solution for a deepening marine shallow cumulus case is obtained, reproducing key aspects of transport and clouds that define this regime. Further investigation of the size statistics of the framework reveals that indirect interactions between size-bins play a key role in the equilibration process. An "acceleration-detrainment" layer is identified above cloud base in which the flux uptake by the largest plumes is counteracted by the detrainment by decelerating smaller plumes. This suppresses CIN, and thus acts to preserve the cloud-subcloud coupling. The convective mass flux shows sensitivity to environmental humidity in the deeper convective cases, reproducing transitions from shallow-to-deep convection. Sensitivity tests are performed to assess the impact of various components of the framework. © 2015. The Authors.


Klevtsov S.,University of Cologne
Journal of High Energy Physics | Year: 2014

We investigate the analogy between the large N expansion in normal matrix models and the asymptotic expansion of the determinant of the Hilb map, appearing in the study of critical metrics on complex manifolds via projective embeddings. This analogy helps to understand the geometric meaning of the expansion of matrix model free energy and its relation to gravitational effective actions in two dimensions. We compute the leading terms of the free energy expansion in the pure bulk case, and make some observations on the structure of the expansion to all orders. As an application of these results, we propose an asymptotic formula for the Liouville action, restricted to the space of the Bergman metrics. © 2014 The Author(s).


Park S.-C.,Catholic University of Korea | Krug J.,University of Cologne
Genetics | Year: 2013

The adaptation of large asexual populations is hampered by the competition between independently arising beneficial mutations in different individuals, which is known as clonal interference. In classic work, Fisher and Muller proposed that recombination provides an evolutionary advantage in large populations by alleviating this competition. Based on recent progress in quantifying the speed of adaptation in asexual populations undergoing clonal interference, we present a detailed analysis of the Fisher-Muller mechanism for a model genome consisting of two loci with an infinite number of beneficial alleles each and multiplicative (nonepistatic) fitness effects. We solve the deterministic, infinite population dynamics exactly and show that, for a particular, natural mutation scheme, the speed of adaptation in sexuals is twice as large as in asexuals. This result is argued to hold for any nonzero value of the rate of recombination. Guided by the infinite population result and by previous work on asexual adaptation, we postulate an expression for the speed of adaptation in finite sexual populations that agrees with numerical simulations over a wide range of population sizes and recombination rates. The ratio of the sexual to asexual adaptation speed is a function of population size that increases in the clonal interference regime and approaches 2 for extremely large populations. The simulations also show that the imbalance between the numbers of accumulated mutations at the two loci is strongly suppressed even by a small amount of recombination. The generalization of the model to an arbitrary number L of loci is briefly discussed. If each offspring samples the alleles at each locus from the gene pool of the whole population rather than from two parents, the ratio of the sexual to asexual adaptation speed is approximately equal to L in large populations. A possible realization of this scenario is the reassortment of genetic material in RNA viruses with L genomic segments. © 2013 by the Genetics Society of America.


Vogeley K.,University of Cologne
Psychopathology | Year: 2013

One essential methodological dichotomy introduced by Karl Jaspers into the field of psychopathology is the difference between 'understanding' ('Verstehen') and 'explaining' ('Erklären'). Jaspers emphasizes a critical epistemological divide between both methods: whereas 'explaining' relates to the attempt to consider mental disorders as consequences of impersonal natural laws, 'understanding' refers to the empathic appreciation of conflicts, hopes, and desires of an individual person. This distinction is related to the difference between 'persons' and 'things' according to Fritz Heider, founder of the so-called 'attribution theory' in social psychology that deals with our ability to ascribe mental states to others. Whereas the behavior of persons is based on psychological rules that are inherently characterized by ambiguity and uncertainty and are thus only partly predictable, the behavior of things is based on natural laws and is therefore fully predictable. This suggests a close resemblance of both accounts where 'understanding' is related to the domain of persons and 'explaining' is related to the domain of things or physical objects. Recently, understanding others has also become a central topic of modern cognitive neuroscience, constituting 'social neuroscience' targeted at explaining our human capacity of ascribing mental states to others. This shows that this distinction introduced by Jaspers still is an important and fundamental differentiation for various research fields dealing with communication and interaction between persons. © 2013 S. Karger AG, Basel.


Larkin J.D.,University of Oxford | Papantonis A.,University of Oxford | Papantonis A.,University of Cologne | Cook P.R.,University of Oxford | Marenduzzo D.,University of Edinburgh
Nucleic Acids Research | Year: 2013

An RNA polymerase has been thought to transcribe by seeking out a promoter, initiating and then tracking down the template. We add tumor necrosis factor a to primary human cells, switch on transcription of a 221-kb gene and monitor promoter position during the ensuing transcription cycle (using RNA fluorescence in situ hybridization coupled to super-resolution localization, chromosome conformation capture and Monte Carlo simulations). Results are consistent with a polymerase immobilized in a 'factory' capturing a promoter and reeling in the template, as the transcript and promoter are extruded. Initially, the extruded promoter is tethered close to the factory and so likely to re-initiate; later, the tether becomes long enough to allow re-initiation in another factory. We suggest close tethering underlies enhancer function and transcriptional 'bursting'. © 2013 The Author(s).


Zazunov A.,Heinrich Heine University Dusseldorf | Altland A.,University of Cologne | Egger R.,Heinrich Heine University Dusseldorf
New Journal of Physics | Year: 2014

We provide a comprehensive theoretical description of low-energy quantum transport for a Coulomb-Majorana junction, where several helical Luttinger liquid nanowires are coupled to a joint mesoscopic superconductor with finite charging energy. Including the Majorana bound states formed near the ends of superconducting wire parts, we derive and analyze the Keldysh phase action describing non-equilibrium charge transport properties of the junction. The low-energy physics corresponds to a two-channel Kondo model with symmetry group SO(M), where M is the number of leads connected to the superconductor. Transport observables, such as the conductance tensor or current noise correlations, display non-trivial temperature or voltage dependences reflecting non-Fermi liquid behavior. © 2014 IOP Publishing and Deutsche Physikalische Gesellschaft.


Maurand R.,CNRS Neel Institute | Meng T.,University of Cologne | Bonet E.,CNRS Neel Institute | Florens S.,CNRS Neel Institute | And 2 more authors.
Physical Review X | Year: 2012

We study a carbon-nanotube quantum dot embedded in a superconducting-quantum-interference-device loop in order to investigate the competition of strong electron correlations with a proximity effect. Depending on whether local pairing or local magnetism prevails, a superconducting quantum dot will exhibit a positive or a negative supercurrent, referred to as a 0 or π Josephson junction, respectively. In the regime of a strong Coulomb blockade, the 0-to-π transition is typically controlled by a change in the discrete charge state of the dot, from even to odd. In contrast, at a larger tunneling amplitude, the Kondo effect develops for an odd-charge (magnetic) dot in the normal state, and quenches magnetism. In this situation, we find that a first-order 0-to-π quantum phase transition can be triggered at a fixed valence when superconductivity is brought in, due to the competition of the superconducting gap and the Kondo temperature. The superconducting-quantum-interference-device geometry together with the tunability of our device allows the exploration of the associated phase diagram predicted by recent theories. We also report on the observation of anharmonic behavior of the current-phase relation in the transition regime, which we associate with the two accessible superconducting states. Our results finally demonstrate that the spin-singlet nature of the Kondo state helps to enhance the stability of the 0 phase far from the mixed-valence regime in odd-charge superconducting quantum dots.


Sierra-Aragon S.,University of Cologne | Walter H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Intervirology | Year: 2012

Inhibition of HIV replication initially targeted viral enzymes, which are exclusively expressed by the virus and not present in the human cell. The development of reverse transcriptase (RT) inhibitors started with the discovery of antiretroviral activity of the nucleoside analog zidovudine in March 1987. Currently, six major classes of antiretroviral drugs are used for the treatment of HIV-infected patients: the RT inhibitors, nucleoside inhibitors and nonnucleoside inhibitors, the protease inhibitors, the integrase inhibitor raltegravir, the fusion inhibitor enfuvirtide (T-20), and the chemokine receptor 5 antagonist maraviroc. A seventh class, the maturation inhibitors, has not yet been approved as their effectiveness is impaired by HIV-1 polymorphisms naturally occurring in 30-40% of HIV-1 therapy-naive isolates. The use of antiretroviral combination therapy has proven to be effective in delaying progression to AIDS and to reconstitute the immune system of HIV-infected individuals. During the last 5 years, the introduction of the newest antiretrovirals has increased treatment efficacy tremendously. However, the development and accumulation of resistance to all antiretroviral drug classes are still a major problem. Additional targets will have to be defined to achieve the ultimate goal: the eradication of the virus from the infected human body. Copyright © 2012 S. Karger AG, Basel.


Hoyer J.,University of Leipzig | Neundorf I.,University of Leipzig | Neundorf I.,University of Cologne
Accounts of Chemical Research | Year: 2012

Over the past two decades, gene therapy has garnered tremendous attention and is heralded by many as the ultimate cure to treat diseases such as cancer, viral infections, and inherited genetic disorders. However, the therapeutic applications of nucleic acids extend beyond the delivery of double-stranded DNA and subsequent expression of deficient gene products in diseased tissue. Other strategies include antisense oligonucleotides and most notably RNA interference (RNAi). Antisense strategies bear great potential for the treatment of diseases that are caused by misspliced mRNA, and RNAi is a universal and extraordinarily efficient tool to knock down the expression of virtually any gene by specific degradation of the desired target mRNA.However, because of the hurdles associated with effective delivery of nucleic acids across a cell membrane, the initial euphoria surrounding siRNA therapy soon subsided. The ability of oligonucleotides to cross the plasma membrane is hampered by their size and highly negative charge. Viral vectors have long been the gold standard to overcome this barrier, but they are associated with severe immunogenic effects and possible tumorigenesis. Cell-penetrating peptides (CPPs), cationic peptides that can translocate through the cell membrane independent of receptors and can transport cargo including proteins, small organic molecules, nanoparticles, and oligonucleotides, represent a promising class of nonviral delivery vectors.This Account focuses on peptide carrier systems for the cellular delivery of various types of therapeutic nucleic acids with a special emphasis on cell-penetrating peptides. We also emphasize the clinical relevance of this research through examples of promising in vivo studies. Although CPPs are often derived from naturally occurring protein transduction domains, they can also be artificially designed. Because CPPs typically include many positively charged amino acids, those electrostatic interactions facilitate the formation of complexes between the carriers and the oligonucleotides. One drawback of CPP-mediated delivery includes entrapment of the cargo in endosomes because uptake tends to be endocytic: coupling of fatty acids or endosome-disruptive peptides to the CPPs can overcome this problem. CPPs can also lack specificity for a single cell type, which can be addressed through the use of targeting moieties, such as peptide ligands that bind to specific receptors. Researchers have also applied these strategies to cationic carrier systems for nonviral oligonucleotide delivery, such as liposomes or polymers, but CPPs tend to be less cytotoxic than other delivery vehicles. © 2012 American Chemical Society.


Vojta M.,University of Cologne
European Physical Journal: Special Topics | Year: 2010

Recent neutron scattering and transport data obtained on underdoped YBa2Cu3O6+δ, with strong signatures of rotation symmetry breaking at low temperatures, point toward electron-nematic order in the charge sector. Such order may originate from a uniform distortion with d-wave symmetry or as a precursor of a uni-directional stripe phase. Here, we discuss whether the neutron scattering data can be linked to incipient charge stripes. We employ and extend a phenomenological model for collective spin and charge fluctuations and analyze the resulting spin excitation spectrum under the influence of lattice anisotropies. Our results show that the experimentally observed temperature-dependent magnetic incommensurability is compatible with a scenario of incipient stripes, the temperature dependence being due to the temperature variation of both strength and correlation length of the charge stripes. Finally, we propose further experiments to distinguish the possible theoretical scenarios. © 2010 EDP Sciences and Springer.


Bucher M.,University of Cologne | Hause B.,Leibniz Institute of Plant Biochemistry | Krajinski F.,Max Planck Institute of Molecular Plant Physiology | Kuster H.,Leibniz University of Hanover
New Phytologist | Year: 2014

Summary: The formation of an arbuscular mycorrhizal (AM) symbiosis is initiated by the bidirectional exchange of diffusible molecules. While strigolactone hormones, secreted from plant roots, stimulate hyphal branching and fungal metabolism, fungal short-chain chitin oligomers as well as sulfated and nonsulfated lipochitooligosaccharides (s/nsMyc-LCOs) elicit pre-symbiosis responses in the host. Fungal LCO signals are structurally related to rhizobial Nod-factor LCOs. Genome-wide expression studies demonstrated that defined sets of genes were induced by Nod-, sMyc- and nsMyc-LCOs, indicating LCO-specific perception in the pre-symbiosis phase. During hyphopodium formation and the subsequent root colonization, cross-talk between plant roots and AM fungi also involves phytohormones. Notably, gibberellins control arbuscule formation via DELLA proteins, which themselves serve as positive regulators of arbuscule formation. The establishment of arbuscules is accompanied by a substantial transcriptional and post-transcriptional reprogramming of host roots, ultimately defining the unique protein composition of arbuscule-containing cells. Based on cellular expression profiles, key checkpoints of AM development as well as candidate genes encoding transcriptional regulators and regulatory microRNAs were identified. Detailed functional analyses of promoters specified short motifs sufficient for cell-autonomous gene regulation in cells harboring arbuscules, and suggested simultaneous, multi-level regulation of the mycorrhizal phosphate uptake pathway by integrating AM symbiosis and phosphate starvation response signaling. © 2014 The Authors.


Manner H.,University of Cologne | Wunsch-Ziegler L.,Gesellschaft fur Innovative Marktforschung MbH
Accident Analysis and Prevention | Year: 2013

We study the severity of accidents on the German Autobahn in the state of North Rhine-Westphalia using data for the years 2009 until 2011. We use a multinomial logit model to identify statistically relevant factors explaining the severity of the most severe injury, which is classified into the four classes fatal, severe injury, light injury and property damage. Furthermore, to account for unobserved heterogeneity we use a random parameter model. We study the effect of a number of factors including traffic information, road conditions, type of accidents, speed limits, presence of intelligent traffic control systems, age and gender of the driver and location of the accident. Our findings are in line with studies in different settings and indicate that accidents during daylight and at interchanges or construction sites are less severe in general. Accidents caused by the collision with roadside objects, involving pedestrians and motorcycles, or caused by bad sight conditions tend to be more severe. We discuss the measures of the 2011 German traffic safety programm in the light of our results. © 2013 Elsevier Ltd.


Keusekotten K.,Medical Research Council Laboratory of Molecular Biology | Elliott P.R.,Medical Research Council Laboratory of Molecular Biology | Glockner L.,Institute of Molecular Toxicology and Pharmacology | Fiil B.K.,Novo Nordisk AS | And 8 more authors.
Cell | Year: 2013

The linear ubiquitin (Ub) chain assembly complex (LUBAC) is an E3 ligase that specifically assembles Met1-linked (also known as linear) Ub chains that regulate nuclear factor κB (NF-κB) signaling. Deubiquitinases (DUBs) are key regulators of Ub signaling, but a dedicated DUB for Met1 linkages has not been identified. Here, we reveal a previously unannotated human DUB, OTULIN (also known as FAM105B), which is exquisitely specific for Met1 linkages. Crystal structures of the OTULIN catalytic domain in complex with diubiquitin reveal Met1-specific Ub-binding sites and a mechanism of substrate-assisted catalysis in which the proximal Ub activates the catalytic triad of the protease. Mutation of Ub Glu16 inhibits OTULIN activity by reducing k cat 240-fold. OTULIN overexpression or knockdown affects NF-κB responses to LUBAC, TNFα, and poly(I:C) and sensitizes cells to TNFα-induced cell death. We show that OTULIN binds LUBAC and that overexpression of OTULIN prevents TNFα-induced NEMO association with ubiquitinated RIPK1. Our data suggest that OTULIN regulates Met1-polyUb signaling. © 2013 Elsevier Inc.


Lienert M.,R2b Energy Consulting GmbH | Lochner S.,University of Cologne
International Journal of Electrical Power and Energy Systems | Year: 2012

The analysis of complex electricity generation systems such as the European one require large scale models based on extensive databases of the relevant infrastructures. Such models are increasingly used to assist policymaking by developing scenarios to investigate the impact of certain policies on generation capacities, investments and prices. The continuing liberalization and interconnection of energy markets thereby requires the considerations of multiple interdependencies with other markets. Most models, however, do not take this into account. This paper develops and applies a large scale electricity investments and dispatch and natural gas market dispatch model to highlight the importance of recognizing interdependencies between power generation and the gas market. In an exemplary analysis, it is demonstrated that seasonal gas price patterns resulting from temperature-dependent household gas demand have a significant impact on the competitiveness of gas-fired power stations in competition with other technologies. Spatially, we show that competitive cost-based gas prices would lead to a relocation of such plants closer to the sources of natural gas. © 2011 Elsevier Ltd. All rights reserved.


Peters F.,University of Cologne
Journal of Investigative Dermatology | Year: 2015

Ceramides are crucial for skin barrier function, but little is known about the regulation of epidermal appendages and whether stem cell populations that control their regeneration depend on specific ceramide species. Here we demonstrate that ceramide synthase 4 (CerS4) is highly expressed in the epidermis of adult mice where it is localized in the interfollicular epidermis and defined populations within the pilosebaceous unit. Inactivation of CerS4 in mice resulted in precocious activation of hair follicle bulge stem cells while expanding the Lrig1+ junctional zone and sebaceous glands. This was preceded first by a decrease in bone morphogenetic protein (BMP) and a subsequent increase in Wnt signaling. This imbalance in quiescent versus activating signals likely promoted a prolonged anagen-like hair follicle state after the second catagen, which exhausted stem cells over time ultimately resulting in hair loss in aged mice. K14-Cre-mediated deletion of CerS4 revealed a similar phenotype, thus suggesting an epidermis intrinsic function of CerS4 in regulating the regeneration of the pilosebaceous unit. The data indicate that CerS4-directed epidermal ceramide composition is essential to control hair follicle stem and progenitor cell behavior potentially through its regulation of BMP and Wnt signaling.Journal of Investigative Dermatology advance online publication, 26 March 2015; doi:10.1038/jid.2015.60. © 2015 The Society for Investigative Dermatology The Society for Investigative DermatologyThe Society for Investigative Dermatology


Vojta M.,University of Cologne
Journal of Low Temperature Physics | Year: 2010

Quantum phase transitions in metals are often accompanied by violations of Fermi liquid behavior in the quantum critical regime. Particularly fascinating are transitions beyond the Landau-Ginzburg-Wilson concept of a local order parameter. The breakdown of the Kondo effect in heavy-fermion metals constitutes a prime example of such a transition. Here, the strongly correlated f electrons become localized and disappear from the Fermi surface, implying that the transition is equivalent to an orbital-selective Mott transition, as has been discussed for multi-band transition-metal oxides. In this article, available theoretical descriptions for orbital-selective Mott transitions will be reviewed, with an emphasis on conceptual aspects like the distinction between different low-temperature phases and the structure of the global phase diagram. Selected results for quantum critical properties will be listed as well. Finally, a brief overview is given on experiments which have been interpreted in terms of orbital-selective Mott physics. © 2010 Springer Science+Business Media, LLC.


Schieck H.P.,University of Cologne
European Physical Journal A | Year: 2010

After an introduction into the essentials of nuclear fusion reactions, being considered for future energy production in fusion reactors, different aspects of using "polarized" particles as fuel are discussed. Special emphasis is given to the four-nucleon system and the D+D reactions. The status of the theory and the experimental data are presented. Predictions for observables in the framework of existing theoretical approaches are given. The necessity of carrying out direct spin-correlated cross-section measurements is accentuated. Details of a future experiment are proposed. © 2010 SIF, Springer-Verlag Berlin Heidelberg.


Altenhein B.,University of Cologne
GLIA | Year: 2015

Development and general organization of the nervous system is comparable between insects and vertebrates. Our current knowledge on the formation of neurogenic anlagen and the generation of neural stem cells is deeply influenced by work done in invertebrate model organisms such as Drosophila and Caenorhabditis elegans. It is the aim of this review to summarize the most important steps in neurogenesis in the Drosophila embryo with a special emphasis on glial cell progenitors and the specification of glial cells. Induction of neurogenic regions during early embryogenesis and determination of neural stem cells are briefly described. Special attention is given to the formation of neural precursors called neuroblasts (NB) and their lineages. NBs divide in a stem cell mode to generate a cell clone of either neurons and/or glial cells. The latter require the activation of the transcription factor glial cells missing (gcm), thus providing a binary switch between neuronal and glial cell fates. Further aspects of glial cell specification and the resulting heterogeneity of the glial population in Drosophila are discussed. © 2015 Wiley Periodicals, Inc.


Borchmann P.,University of Cologne
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2010

Hodgkin lymphoma (HL) has become a curable malignancy for most patients during the last decades. However, many controversies still exist on the optimal strategy of how to cure our patients. The key question is how to balance the risks and toxicities of chemotherapy and radiotherapy against the need for a definite treatment for early or advanced-stage HL patients. However, although many studies have been conducted and reported during the past decade, interpretation of their results and treatment recommendations might vary significantly in different countries. For example, early-stage HL might be divided into two different subgroups: early favorable and early unfavorable or not. Treatment of early-stage HL might include radiotherapy ("combined modality") or not. Depending on the extent of radiotherapy, the schedule and number of chemotherapy cycles are also questioned. For advanced-stage HL, the situation is not much different. Compared with ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine), the more aggressive escalated BEACOPP regimen (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) is highly effective, but also raises concern due to excessive toxicity. Thus, there is a controversy about the standard of care for advanced HL patients. Because no mature results comparing these approaches with each other are currently available, it remains our duty to share the preliminary information with our patients and to figure out the most appropriate individual treatment strategy. Of course, the discussion of these issues is influenced by experiences and preferences. In contrast, in this article, we will try to focus on the available scientific evidence regarding the first-line treatment of HL. Of course, focusing on the last decade necessarily exclude the most recent results from ongoing studies. Thus, even though this article comprises treatment recommendations for HL patients, the best treatment certainly still is within properly designed prospective clinical trials.


Dreiseidler T.,University of Cologne
The International journal of oral & maxillofacial implants | Year: 2012

To evaluate the accuracy of a newly developed open-source system for three-dimensional dental implant planning and fully guided dental implant placement. Forty-eight implant positions were planned for eight partially edentulous anatomical patient equivalent models with an open-source implant planning system on the basis of cone beam computed tomography (CBCT) scans. The virtual software planning leads to an output of four different coordinates for each implant position; with these, surgical guides were manufactured using a coordinate-transfer apparatus. During the surgical simulation, drills and implants were fully guided as they were inserted by means of the harmonized components of the vendor's sleeve-in-sleeve system. After follow-up CBCT investigation and reference marker-based software registration, linear horizontal, vertical, and maximal 3D deviations, as well as angular deviations, between the virtual planning data and the surgical results were calculated. The mean three-dimensional deviation values for the final implant positions were 671 μm (95% confidence interval [CI] 452 to 891 μm) at the implant base and 808 μm (95% CI 646 to 971 μm) at the implant tip. Mean vertical deviations were 273 μm (95% CI 200 to 345 μm). Mean angular deviations of 1.9 degrees (95% CI 1.4 to 2.4 degrees) were measured. The open-source implant planning system described in this study demonstrated a level of accuracy that is equal or superior to most descriptions of the literature on computer-aided implant dentistry, allows for predictable implant positioning, and has the potential to reduce postoperative impairment versus conventional implant insertion.


Higgins P.G.,University of Cologne
Journal of medical microbiology | Year: 2012

We have investigated the reproducibility of DiversiLab rep-PCR fingerprints between two laboratories with the aim of determining if the fingerprints and clustering are laboratory-specific or portable. One-hundred non-duplicate Acinetobacter baumannii isolates were used in this study. DNA isolation and rep-PCR were each performed separately in two laboratories and rep-PCR patterns generated in laboratory A were compared with those from laboratory B. Twelve A. baumannii isolates processed in laboratory A showed ≥98 % pattern similarity with the corresponding 12 isolates tested in laboratory B and were considered identical. Sixty-four isolates showed 95-97.9 % similarity with their corresponding isolates. Twenty-three isolates showed 90-94 % similarity with the corresponding isolates, while one isolate showed only 87.4 % similarity. However, intra-laboratory clustering was conserved: isolates that clustered in laboratory A also clustered in laboratory B. While clustering was conserved and reproducible at two different laboratories, demonstrating the robustness of rep-PCR, interlaboratory comparison of individual isolate fingerprints showed more variability. This comparison allows conclusions regarding clonality to be reached independent of the laboratory where the analysis is performed.


Petermann F.,University of Bremen | Lehmkuhl G.,University of Cologne
Kindheit und Entwicklung | Year: 2010

Previous studies have shown that a high number of young people have experienced violent behavior - as a victim as well as an offender. High monetary and psychosocial costs demand effective programs for the prevention of aggressive behavior, and interventions addressing individual circumstances. Various approaches to prevent the development of aggressive behavior and intervention programs care presented, which are directed at children as well as at parents and teachers. The main focus will be on early recognition and prevention as it is of high importance to prevent its development as early as possible. © Hogrefe Verlag, Göttingen 2010.


The myokine irisin has been proposed to regulate energy homeostasis. Little is known about its association with metabolic parameters and especially with parameters influencing pathways of lipid metabolism. In the context of a clinical trial, an exploratory post hoc analysis has been performed in healthy subjects to determine whether simvastatin and/or ezetimibe influence serum irisin levels. The direct effects of simvastatin on irisin were also examined in primary human skeletal muscle cells (HSKMCs). A randomized, parallel 3-group study was performed in 72 men with mild hypercholesterolemia and without apparent cardiovascular disease. Each group of 24 subjects received a 14-day treatment with either simvastatin 40 mg, ezetimibe 10 mg, or their combination. Baseline irisin concentrations were not significantly correlated with age, BMI, estimated GFR, thyroid parameters, glucose, insulin, lipoproteins, non-cholesterol sterols, adipokines, inflammation markers and various molecular markers of cholesterol metabolism. Circulating irisin increased significantly in simvastatin-treated but not in ezetimibe-treated subjects. The changes were independent of changes in LDL-cholesterol and were not correlated with changes in creatine kinase levels. In HSKMCs, simvastatin significantly increased irisin secretion as well as mRNA expression of its parent peptide hormone FNDC5. Simvastatin significantly induced cellular reactive oxygen species levels along with expression of pro- and anti-oxidative genes such as Nox2, and MnSOD and catalase, respectively. Markers of cellular stress such as atrogin-1 mRNA and Bax protein expression were also induced by simvastatin. Decreased cell viability and increased irisin secretion by simvastatin was reversed by antioxidant mito-TEMPO, implying in part that irisin is secreted as a result of increased mitochondrial oxidative stress and subsequent myocyte damage. Simvastatin increases irisin concentrations in vivo and in vitro. It remains to be determined whether this increase is a result of muscle damage or a protective mechanism against simvastatin-induced cellular stress. ClinicalTrials.gov NCT00317993 NCT00317993.


Tokano T.,University of Cologne
Ocean Dynamics | Year: 2010

Numerous hydrocarbon lakes have recently been detected on Saturn's largest moon Titan, representing the only known large bodies of liquids on a planetary surface outside the Earth. In the context of comparative oceanography, tides and tidal currents in two representative lakes on Titan (Kraken Mare and Ontario Lacus) are simulated by a three-dimensional baroclinic ocean circulation model. Since the tide-generating force on Titan is an order of magnitude larger than on Earth and the gravitational acceleration is small, tides and currents are substantially larger than in Earth's lakes and are more comparable with those in Earth's oceans. The predicted maximum tidal range in Kraken Mare is 4 m. The tidal wave propagates around the basin of Kraken Mare, while a nearly standing tidal wave is excited in Ontario Lacus. Titan's rotation is too slow to affect the tidal flow in any Titan's lake. The tidal current velocity in Kraken Mare amounts to a few centimeters per second except in the vicinity of a narrow strait, where it is enhanced by an order of magnitude. In summer, when the lake is stratified, internal tides can develop. Seiches cannot be caused by tide. In the largest lakes, atmospheric tide may cause additional lake surface displacements. © 2010 Springer-Verlag.


Held P.,University of Cologne
Acta Crystallographica Section E: Structure Reports Online | Year: 2014

In the title salt, (C2H8N)2[Ni(H2O)6)](SO4)2·2H2O, the NiII cation is located on a centre of inversion and exhibits a slightly distorted octahedral arrangement of water molecules. The Ni - O bond lengths in the complex [Ni(H2O)6]2+ cation show a distribution as in the related Tutton salt (NH4)2[Ni(H2O)6](SO4)2, but are longer in average [2.056 (13) versus 2.037 (12) Å]. The noncoordinating water molecules and dimethylammonium cations connect the sulfate and [Ni(H2O)6]2+ octahedra via O - H⋯O and N - H⋯O hydrogen bonds from weak up to medium strength into a three-dimensional framework whereby the complex metal cations and sulfate anions are arranged in sheets parallel (001).


Bewernick B.H.,University of Bonn | Kayser S.,University of Bonn | Sturm V.,University of Cologne | Schlaepfer T.E.,University of Bonn | Schlaepfer T.E.,Johns Hopkins University
Neuropsychopharmacology | Year: 2012

Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) was associated with antidepressant, anxiolytic, and procognitive effects in a small sample of patients suffering from treatment-resistant depression (TRD), followed over 1 year. Results of long-term follow-up of up to 4 years of NAcc-DBS are described in a group of 11 patients. Clinical effects, quality of life (QoL), cognition, and safety are reported. Eleven patients were stimulated with DBS bilateral to the NAcc. Main outcome measures were clinical effect (Hamilton Depression Rating Scale, Montgomery-Asperg Rating Scale of Depression, and Hamilton Anxiety Scale) QoL (SF-36), cognition and safety at baseline, 12 months (n11), 24 months (n=10), and last follow-up (maximum 4 years, n=5). Analyses were performed in an intent-to-treat method with last observation carried forward, thus 11 patients contributed to each point in time. In all, 5 of 11 patients (45%) were classified as responders after 12 months and remained sustained responders without worsening of symptoms until last follow-up after 4 years. Both ratings of depression and anxiety were significantly reduced in the sample as a whole from first month of NAcc-DBS on. All patients improved in QoL measures. One non-responder committed suicide. No severe adverse events related to parameter change were reported. First-time, preliminary long-term data on NAcc-DBS have demonstrated a stable antidepressant and anxiolytic effect and an amelioration of QoL in this small sample of patients suffering from TRD. None of the responders of first year relapsed during the observational period (up to 4 years). © 2012 American College of Neuropsychopharmacology. All rights reserved.


Fiener P.,University of Cologne | Auerswald K.,TU Munich | Van Oost K.,Catholic University of Louvain
Earth-Science Reviews | Year: 2011

Surface runoff and associated erosion processes adversely affect soil and surface water quality. There is increasing evidence that a sound understanding of spatial-temporal dynamics of land use and management are crucial to understanding surface runoff processes and underpinning mitigation strategies. In this review, we synthesise the effects of (1) temporal patterns of land management of individual fields, and (2) spatio-temporal interaction of several fields within catchments by applying semivariance analysis, which allows the extent and range of the different patterns to be compared. Consistent effects of management on the temporal dynamics of surface runoff of individual fields can be identified, some of which have been incorporated into small-scale hydrological models. In contrast, the effects of patchiness, the spatial organisation of patches with different soil hydrological properties, and the effects of linear landscape structures are less well understood and are rarely incorporated in models. The main challenge for quantifying these effects arises from temporal changes within individual patches, where the largest contrasts usually occur in mid-summer and cause a seasonally varying effect of patchiness on the overall catchment response. Some studies indicate that increasing agricultural patchiness, due to decreasing field sizes, reduces the catchment-scale response to rainfall, especially in cases of Hortonian runoff. Linear structures associated with patchiness of fields (e.g. field borders, ditches, and ephemeral gullies) may either increase or decrease the hydraulic connectivity within a catchment. The largest gap in research relates to the effects and temporal variation of patch interaction, the influence of the spatial organisation of patches and the interaction with linear structures. In view of the substantial changes in the structure of agricultural landscapes occurring throughout the world, it is necessary to improve our knowledge of the influence of patchiness and connectivity, and to implement this knowledge in new modelling tools. © 2011 Elsevier B.V.


Maier B.,University of Cologne | Wong G.C.L.,California Nano Systems Institute
Trends in Microbiology | Year: 2015

The bacterial type IV pilus (T4P) is a versatile molecular machine with a broad range of functions. Recent advances revealed that the molecular components and the biophysical properties of the machine are well conserved among phylogenetically distant bacterial species. However, its functions are diverse, and include adhesion, motility, and horizontal gene transfer. This review focusses on the role of T4P in surface motility and bacterial interactions. Different species have evolved distinct mechanisms for intracellular coordination of multiple pili and of pili with other motility machines, ranging from physical coordination to biochemical clocks. Coordinated behavior between multiple bacteria on a surface is achieved by active manipulation of surfaces and modulation of pilus-pilus interactions. An emerging picture is that the T4P actively senses and responds to environmental conditions. © 2015 Elsevier Ltd.


Choi Y.-H.,University of Cologne | Kurtz A.,Berlin Brandenburg Center for Regenerative Therapies | Kurtz A.,Charite - Medical University of Berlin | Stamm C.,Berlin Brandenburg Center for Regenerative Therapies
Human Gene Therapy | Year: 2011

Despite refinements of medical and surgical therapies, heart failure remains a fatal disease. Myocardial infarction is the most common cause of heart failure, and only palliative measures are available to relieve symptoms and prolong the patient's life span. Because mammalian cardiomyocytes irreversibly exit the cell cycle at about the time of birth, the heart has traditionally been considered to lack any regenerative capacity. This paradigm, however, is currently shifting, and the cellular composition of the myocardium is being targeted by various regeneration strategies. Adult progenitor and stem cell treatment of diseased human myocardium has been carried out for more than 10 years (Menasche et al., 2001; Stamm et al., 2003), and it has become clear that, in humans, the regenerative capacity of hematopoietic stem cells and endothelial progenitor cells, despite potent proangiogenic effects, is limited (Stamm et al., 2009). More recently, mesenchymal stem cells (MSCs) and related cell types are being evaluated in preclinical models of heart disease as well as in clinical trials (see Published Clinical Trials, below). MSCs have the capacity to self-renew and to differentiate into lineages that normally originate from the embryonic mesenchyme (connective tissues, blood vessels, blood-related organs) (Caplan, 1991; Prockop, 1997; Pittenger et al., 1999). The current definition of MSCs includes plastic adherence in cell culture, specific surface antigen expression (CD105 +/CD90 +/CD73 +, CD34 -/CD45 -/CD11b - or CD14 -/CD19 - or CD79α -/HLA-DR1 -), and multilineage in vitro differentiation potential (osteogenic, chondrogenic, and adipogenic) (Dominici et al., 2006). If those criteria are not met completely, the term "mesenchymal stromal cells" should be used for marrow-derived adherent cells, or other terms for MSC-like cells of different origin. For the purpose of this review, MSCs and related cells are discussed in general, and cell type-specific properties are indicated when appropriate. We first summarize the preclinical data on MSCs in models of heart disease, and then appraise the clinical experience with MSCs for cardiac cell therapy. © 2011 Mary Ann Liebert, Inc.


Becker M.,IRD Montpellier | Karpytchev M.,CNRS Coastal and Marine Environment Laboratory | Lennartz-Sassinek S.,University of Cologne
Geophysical Research Letters | Year: 2014

Detection and attribution of human influence on sea level rise are important topics that have not yet been explored in depth. We question whether the sea level changes (SLC) over the past century were natural in origin. SLC exhibit power law long-term correlations. By estimating Hurst exponent through Detrended Fluctuation Analysis and by applying statistics of Lennartz and Bunde [], we search the lower bounds of statistically significant external sea level trends in longest tidal records worldwide. We provide statistical evidences that the observed SLC, at global and regional scales, is beyond its natural internal variability. The minimum anthropogenic sea level trend (MASLT) contributes to the observed sea level rise more than 50% in New York, Baltimore, San Diego, Marseille, and Mumbai. A MASLT is about 1mm/yr in global sea level reconstructions that is more than half of the total observed sea level trend during the XXth century. Key Points Long-term persistence impacts on sea level rise estimation Sea level change is clearly unnatural in two thirds of the longest tidal records Sea level change magnitude cannot be explained without human influence © 2014. American Geophysical Union. All Rights Reserved.


Barbui T.,Ospedale Papa Giovanni XXIII | Thiele J.,University of Cologne | Vannucchi A.M.,University of Florence | Tefferi A.,Mayo Medical School
Leukemia | Year: 2014

The aim of this review is to critically address the validity and clinical applicability of three major diagnostic classification systems for polycythemia vera (PV), that is, those proposed by the Polycythemia Vera Study Group (PVSG), the British Committee for Standards in Haematology (BCSH) and the World Health Organization (WHO). Special focus is on which one of the three red cell parameters (hemoglobin - HB, hematocrit - HCT and red cell mass - RCM) should be used as the diagnostic hallmark of PV. The revised BCSH employed a persistently raised HCT level as the first diagnostic criterion in combination with the presence of a JAK2V617F mutation. On the other hand, the WHO classification used a raised HB value as a surrogate for increased RCM in association with molecular markers and for the first time, the bone marrow (BM) morphology was included as a minor criterion. Ongoing controversy and discussion regards the use of certain threshold values for HCT and HB as surrogates for RCM as well as the existence of prodromal-latent disease, so-called masked PV (mPV). It has been shown that mPV can be recognized in patients not meeting the required HB or HCT threshold levels by both the WHO and BCSH criteria. These cases present with the same baseline clinical features as overt PV but present worsened survival. A critical reappraisal of the WHO criteria may suggest either to reduce the thresholds for HB or to consider HCT values as major diagnostic criterion, as in the BCSH, in association with JAK2V617F mutation. The clinical utility of using HCT as reference variable is supported also by results of clinical trials which explicitly recommend to use the HCT threshold for monitoring treatment. In questionable cases as in mPV, BM biopsy examinations should be mandated together with mutation analysis. © 2014 Macmillan Publishers Limited.


Tefferi A.,Mayo Medical School | Thiele J.,University of Cologne | Vannucchi A.M.,University of Florence
Leukemia | Year: 2014

Disease-specific mutations facilitate diagnostic precision and drug target discovery. In myeloproliferative neoplasms (MPN), this is best exemplified by the chronic myeloid leukemia-associated BCR-ABL1. No other mutation in MPN has thus far shown a similar degree of diagnostic accuracy or therapeutic relevance. However, JAK2 and KIT mutations are detected in more than 90% of patients with polycythemia vera and systemic mastocytosis, respectively, and are therefore used as highly sensitive clonal markers in these diseases. JAK2 and MPL mutations also occur in essential thrombocythemia (ET) and primary myelofibrosis (PMF), but their diagnostic value is limited by suboptimal sensitivity and specificity. The molecular diagnostic gap in JAK2/MPL-unmutated ET/PMF is now partially addressed by the recent discovery of calreticulin (CALR) mutations in the majority of such cases. However, bone marrow morphology remains the central diagnostic platform and is essential for distinguishing ET from prefibrotic PMF and diagnosing patients those do not express JAK2, MPL or CALR (triple-negative). The year 2013 was also marked by the description of CSF3R mutations in the majority of patients with chronic neutrophilic leukemia (CNL). Herein, we argue for the inclusion of CALR and CSF3R mutations in the World Health Organization classification system for ET/PMF and CNL, respectively. © 2014 Macmillan Publishers Limited.


Happe A.,University of Cologne
The International journal of periodontics & restorative dentistry | Year: 2013

Thin facial soft tissue may lead to visible soft tissue discoloration around implants and therefore to esthetic deficiencies. The aim of this article is to present a surgical approach to peri-implant soft tissue discoloration caused by the shinethrough effects of restorative materials in the anterior maxilla. A clinical case is used to illustrate the approach. A minimally invasive tunneling approach and connective tissue graft are used. The optical outcome is documented in an objective and standardized manner using a spectrophotometer after a follow-up of 12 months. The presented technique clearly improved the clinical condition and esthetic outcome. Spectrophotometric follow-up revealed a soft tissue color difference between the implant and adjacent tooth (control) that was clearly less than initially presented. In the area 3 mm apical to the soft tissue margin, this difference was beneath the clinically perceptible threshold of 3.7.


Rosenkranz S.,University of Cologne | Preston I.R.,Tufts Medical Center
European Respiratory Review | Year: 2015

Right heart catheterisation (RHC) plays a central role in identifying pulmonary hypertension (PH) disorders, and is required to definitively diagnose pulmonary arterial hypertension (PAH). Despite widespread acceptance, there is a lack of guidance regarding the best practice for performing RHC in clinical practice. In order to ensure the correct evaluation of haemodynamic parameters directly measured or calculated from RHC, attention should be drawn to standardising procedures such as the position of the pressure transducer and catheter balloon inflation volume. Measurement of pulmonary arterial wedge pressure, in particular, is vulnerable to over- or under-wedging, which can give rise to false readings. In turn, errors in RHC measurement and data interpretation can complicate the differentiation of PAH from other PH disorders and lead to misdiagnosis. In addition to diagnosis, the role of RHC in conjunction with noninvasive tests is widening rapidly to encompass monitoring of treatment response and establishing prognosis of patients diagnosed with PAH. However, further standardisation of RHC is warranted to ensure optimal use in routine clinical practice. © ERS 2015.


Lordick F.,University of Leipzig | Holscher A.H.,University of Cologne | Haustermans K.,Catholic University of Leuven | Wittekind C.,University of Leipzig
Langenbeck's Archives of Surgery | Year: 2013

Background: The treatment of localized esophageal cancer has been debated controversially over the past decades. Neoadjuvant treatment was used empirically, but evidence was limited due to the lack of high-quality confirmatory studies. Meanwhile, data have become much clearer due to recently published well-conducted randomized controlled trials and meta-analyses. Methods: Neoadjuvant and perioperative platinum fluoropyrimidine-based combination chemotherapy has now an established role in the treatment of stage II and stage III esophageal adenocarcinoma and cancer of the esophago-gastric junction. Neoadjuvant chemoradiation is now the standard of care for treating stage II and stage III esophageal squamous cell cancer and can also be considered for treating esophageal adenocarcinoma. Results: Patients with esophageal squamous cell cancer treated with definitive chemoradiation achieve comparable long-term survival compared with surgery. Short-term mortality is less with chemoradiation alone, but local tumor control is significantly better with surgery. Conclusion: This expert review article outlines current data and literature and delineates recommendable treatment guidelines for localized esophageal cancer. © 2012 Springer-Verlag.


Glockner A.,BDH Klinik Greifswald | Cornely O.A.,University of Cologne
Mycoses | Year: 2013

Recent guideline recommendations on the management of candidaemia provide valuable treatment guidance for routine clinical practice, but need to be interpreted in the light of the actual situation of the patient and the local epidemiology of fungal infections. Echinocandins emerge as the generally preferred primary treatment. Treatment should be initiated immediately after notification of a Candida-positive blood culture in all patients. Ambiguous issues include the definition of optimum duration of treatment, the indication and time point to step down to oral azoles, catheter management, and the appropriate approach in critically ill patients at high risk for candidaemia in the absence of definitive proof of infection. Patients with clinical suspicion of antifungal treatment failure need prompt workup for adequacy of treatment, focal sources of sustained infection and potential superinfection. © 2012 Blackwell Verlag GmbH.


Hoffmann K.,Institute of Medical Genetics | Heller R.,University of Cologne
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

Normally, one inherits one chromosome of each pair from one parent and the second chromosome from the other parent. Uniparental disomy (UPD) describes the inheritance of both homologues of a chromosome pair from the same parent. The biological basis of UPD syndromes is disturbed genomic imprinting. The consequences of UPD depend on the specific chromosome/segment involved and its parental origin. Phenotypes range from unapparent to unmasking of an autosomal-recessive disease to presentation as a syndromic imprinting disorder. Whilst paternal UPD(7) is clinically unapparent, maternal UPD(7) is one of several causes of Silver-Russell syndrome. Presentation of paternal UPD(14) ("Kagami syndrome") is a thoracic dysplasia syndrome with mental retardation and limited survival. Findings in maternal UPD(14) ("Temple") syndrome show an age-dependent overlap with the well-known maternal UPD(15) (Prader-Willi) syndrome and are dominated by initial failure to thrive followed by obesity, learning difficulties and precocious puberty. Diagnostic strategies to tackle the genetic heterogeneity of UPD(7) and UPD(14) syndromes will be explained. Management issues in UPD(7) and UPD(14) patients will be discussed, and finally areas requiring further research will be outlined. © 2010 Elsevier Ltd. All rights reserved.


Recently, Gao et al. and Chappie et al. elucidated the crystal structures of the polytetrameric stalk domain of the dynamin-like virus resistance protein, MxA, and of the G-domain dimer of the large, membrane-deforming GTPase, dynamin, respectively. Combined, they provide a hypothetical oligomeric structure for the complete dynamin protein. Here, it is discussed how the oligomers are expected to form and how they participate in dynamin mediated vesicle fission during the process of endocytosis. The proposed oligomeric structure is compared with the novel mechanochemical model of dynamin function recently proposed by Bashkirov et al. and Pucadyil and Schmid. In conclusion, the new model of the dynamin oligomer has the potential to explain how short self-limiting fissogenic dynamin assemblies are formed and how concerted GTP hydrolysis is achieved. The oligomerisation of two other dynamin superfamily proteins, the guanylate binding proteins (GBPs) and the immunity-related GTPases (IRGs), is addressed briefly. © 2010 WILEY Periodicals, Inc.


Wu H.,University of Cologne
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

Electronic and magnetic structures of the recently synthesized cobalt oxyselenide La2 Co2 Se2 O3 (structurally similar to the superconducting iron pnictides) are studied through density-functional calculations. The obtained results show that this material is a Mott insulator and it has a very stable Co2+ high-spin ground state with a t2g -like orbital ordering, which is substantiated by the calculated crystal-field excitation energies. The square lattice of the Co2+ spins is found to have a strong antiferromagnetic (a weak ferromagnetic) coupling for the second-nearest neighbors via O (Se2) and an intermediate antiferromagnetic one for the first-nearest neighbors with the strength ratio about 10:1:3. The present results account for the available experimental data and the prediction of a planar frustrated (2×2) antiferromagnetic structure would motivate a new experiment. © 2010 The American Physical Society.


Gather M.C.,University of Iceland | Gather M.C.,Harvard University | Meerholz K.,University of Cologne | Danz N.,Fraunhofer Institute for Applied Optics and Precision Engineering | Leosson K.,University of Iceland
Nature Photonics | Year: 2010

Plasmonicsthe study of the interaction between electromagnetic waves and electron plasmas on metal surfaces and in metallic nanostructureshas received much attention in recent years, with potential new applications ranging from subwavelength photonic circuits to photothermal cancer therapy. In many cases, however, the substantial attenuation of the electromagnetic wave due to absorption (ohmic loss) in the metal is of serious concern. Introduction of optical gain into the dielectric material adjacent to the metal surface has been identified as a means of compensating for the absorption loss, but the experimental realization of lossless propagation or optical gain in plasmonic waveguides has proven elusive. Here, we demonstrate direct proof of plasmonic propagation with net positive gain over macroscopic distances. The gain is provided by an optically pumped layer of fluorescent conjugated polymer adjacent to the metal surface in a dielectric-metal-dielectric plasmonic waveguide. © 2010 Macmillan Publishers Limited. All rights reserved.


Bschor T.,Jewish Hospital of Berlin | Bschor T.,TU Dresden | Baethge C.,University of Cologne
Acta Psychiatrica Scandinavica | Year: 2010

Objective: Switching antidepressants is a common strategy for managing treatment-resistant depressed patients. However, no systematic reviews have been conducted to date. Method: We systematically searched MEDLINE/EMBASE/Cochrane Central Register of Controlled Trials and additional sources. We included double-blind studies of patients with depressive symptomatology who were not responding to initial antidepressant monotherapy and were subsequently randomized to another antidepressant or to continue the same antidepressant. Results were pooled for meta-analysis of response + remission rates using a fixed-effects model. Results: A total of three studies were included. Switching to another antidepressant was not superior to continuing the initial antidepressant in any of these studies. Our meta-analysis showed no significant advantages to either strategy and no significant heterogeneity of results [OR for response rates: 0.85 (95% CI: 0.55-1.30) favoring continuing]. Conclusion: There is a discrepancy between the published evidence and the frequent decision to switch antidepressants, indicating an urgent need for more controlled studies. Pending such studies we recommend that physicians rely on more thoroughly evaluated strategies. © 2009 John Wiley & Sons A/S.


Bergami M.,University of Cologne
Communicative and Integrative Biology | Year: 2015

In contrast to most areas of the adult brain, the dentate gyrus (DG) of the hippocampus is endowed with the capability to generate new neurons life-long. While recent evidence suggests that these adult-born neurons exert specialized functions in information processing compared to pre-existing DG granule neurons, to which extent the establishment of their evolving connectivity may be regulated by experience has been elusive. We recently demonstrated that environmental enrichment (EE) induces a surprising input-specific reorganization of the presynaptic connectivity of adultborn neurons, and that this form of structural plasticity appears to large degree confined to a defined period of few weeks shortly after their generation. Here, I briefly discuss how these findings may uncover a previously unknown layer of complexity in the processes regulating the synaptic integration of adult-born neurons and propose that their circuit incorporation within the pre-existing hippocampal network is not prefigured but rather modulated by specific experiences. Synaptic plasticity of adult-born hippocampal neurons © Matteo Bergami.


Rindler-Daller T.,University of Texas at Austin | Rindler-Daller T.,University of Cologne | Shapiro P.R.,University of Texas at Austin
Monthly Notices of the Royal Astronomical Society | Year: 2012

Various extensions of the standard model of particle physics predict the existence of very light bosons, with masses ranging from about 10 -5eV for the QCD axion down to 10 -33eV for ultra-light particles. These particles could be responsible for all or part of the cold dark matter (CDM) in the Universe. For such particles to serve as CDM, their phase-space density must be high enough to form a Bose-Einstein condensate (BEC). The fluid-like nature of BEC-CDM dynamics differs from that of standard collisionless CDM, however, so different signature effects on galactic haloes may allow observations to distinguish them. Standard CDM has problems with galaxy observations on small scales; cuspy central density profiles of haloes and the overabundance of subhaloes seem to conflict with observations of dwarf galaxies. It has been suggested that BEC-CDM can overcome these shortcomings for a large range of particle mass m and self-interaction coupling strength g. For quantum coherence to influence structure on the scale of galactic haloes of radius R and mass M, either the de-Broglie wavelength λ deB≲R, which requires m≳m H≅ 10 -25(R/100kpc) -1/2(M/10 12M ⊙) -1/2eV, or else λ deB≪R but gravity is balanced by self-interaction, which requires m≫m Handg≫g H≅ 2 × 10 -64(R/100kpc)(M/10 12M ⊙) -1 eV cm 3. Here we study the largely neglected effects of angular momentum on BEC haloes. Dimensionless spin parameters λ≃ 0.05 are expected from tidal-torquing by large-scale structure formation, just as for standard CDM. Since laboratory BECs develop quantum vortices if rotated rapidly enough, we ask whether this amount of angular momentum is sufficient to form vortices in BEC haloes, which would affect their structure with potentially observable consequences. The minimum angular momentum required for a halo to sustain a vortex, L QM, corresponds to ℏ per particle, or ℏM/m. For λ= 0.05, this requires m≥ 9.5m H, close enough to the particle mass required to influence structure on galactic scales that BEC haloes may be subject to vortex formation. While this is a necessary condition, it is not sufficient. To determine if and when quantum vortices will form in BEC haloes with a given λ-value, we study the equilibrium of self-gravitating, rotating, virialized BEC haloes which satisfy the Gross-Pitaevskii-Poisson equations, and calculate under what conditions vortices are energetically favoured, in two limits: either just enough angular momentum for one vortex or a significant excess of angular momentum. For λ= 0.05, vortex formation is energetically favoured for L/L QM≥ 1 as long as bothm/m H≥ 9.5 andg/g H≥ 68.0. Hence, vortices are expected for a wide range of BEC parameters. However, vortices cannot form for vanishing self-interaction (i.e. when λ deB≲R), and a range of particle parameters also remain even for BEC haloes supported by self-interaction, for which vortices will not form. Such BEC haloes can be modelled by compressible, (n= 1)-polytropic, irrotational Riemann-S ellipsoids. © 2012 The Authors Monthly Notices of the Royal Astronomical Society © 2012 RAS.


Bauer K.,University of Cologne
Cochrane database of systematic reviews (Online) | Year: 2012

Chronic lymphocytic leukaemia (CLL) accounts for 25% of all leukaemias and is the most common lymphoid malignancy in western countries. Standard treatments include mono- or polychemotherapies, usually combined with monoclonal antibodies such as rituximab or alemtuzumab. However, the impact of these agents remains unclear, as there are hints for increased risk of severe infections. The objectives of this review are to provide an evidence-based answer regarding the clinical benefits and harms of monoclonal anti-CD20 antibodies (such as rituximab, ofatumumab, GA101) compared to no further therapy or to other anti-leukaemic therapies in patients with CLL, irrespective of disease status. We searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 12, 2011), MEDLINE (from January 1990 to 4 January 2012), and EMBASE (from 1990 to 20 March 2009) as well as conference proceedings (American Society of Hematology, American Society of Clinical Oncology, European Hematology Association and European Society of Medical Oncology) for randomised controlled trials (RCTs). We included RCTs examining monoclonal anti-CD20 antibodies compared to no further therapy or to anti-leukaemic therapy such as chemotherapy or monoclonal antibodies in patients with newly diagnosed or relapsed CLL. We used hazard ratios (HR) as effect measures for overall survival (OS), progression-free survival (PFS) and time to next treatment, and risk ratios (RR) for response rates, treatment-related mortality (TRM) and adverse events (AEs). Two review authors independently extracted data and assessed quality of trials. We screened a total of 1150 records. Seven RCTs involving 1763 patients were identified, but only five could be included in the two separate meta-analyses we performed. We judged the overall the quality of these trials as moderate to high. All trials were randomised and open-label studies. However, two trials were published as abstracts only, therefore we were unable to assess the potential risk of bias for these trials in detail.Three RCTs (N = 1421) assessed the efficacy of monoclonal anti-CD20 antibodies (i.e. rituximab) plus chemotherapy compared to chemotherapy alone. The meta-analyses showed a statistically significant OS (HR 0.78, 95% confidence interval (CI) 0.62 to 0.98, P = 0.03, the number needed to treat for an additional beneficial effect (NNTB) was 12) and PFS (HR 0.64, 95% CI 0.55 to 0.74, P < 0.00001) advantage for patients receiving rituximab. In the rituximab-arm occurred more AEs, World Health Organization (WHO) grade 3 or 4 (3 trials, N = 1398, RR 1.15, 95% CI 1.08 to 1.23, P < 0.0001; the number needed to harm for an additional harmful outcome (NNTH) was 9), but that did not lead to a statistically significant difference regarding TRM (3 trials, N = 1415, RR 1.19, 95% CI 0.70 to 2.01, P = 0.52).Two trials (N = 177) evaluated rituximab versus alemtuzumab. Neither study reported OS or PFS. There was no statistically significant difference between arms regarding complete response rate (CRR) (RR 1.21, 95% CI 0.94 to 1.58, P = 0.14) or TRM (RR 0.31, 95% CI 0.06 to 1.51, P = 0.15).


Bergner N.,University of Cologne
Cochrane database of systematic reviews (Online) | Year: 2012

Primary central nervous system lymphoma (PCNSL) is a variant of extranodal non-Hodgkin lymphoma (NHL) that accounts for about 2% to 5% of all primary intracranial tumours with immunocompetent patients. It appears at a median age of 62 years. A standard of care for PCNSL patients has not been defined yet, but high-dose methotrexate (HD-MTX) is considered to be a beneficial chemotherapy in PCNSL treatment. Currently, HD-MTX is combined with numerous other chemotherapy drugs to improve outcomes of HD-MTX monotherapy. However, the impact of additional chemotherapy remains unclear, as there is evidence of a higher risk of adverse events (AEs) such as infective complications. We performed a systematic review of randomised controlled trials (RCTs) to assess the efficacy and safety of additional chemotherapy to HD-MTX in the treatment of immunocompetent PCNSL patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5) and MEDLINE (from 1950 to May 2012) as well as conference proceedings for RCTs. Two review authors (NB, NS) independently screened search results. We included RCTs comparing HD-MTX in combination with additional chemotherapy to mono-chemotherapy with HD-MTX in immunocompetent patients off all ages in first-line treatment of PCNSL. As an effect measure we used hazard ratios (HR) and 95% confidence intervals (CI) for overall survivals (OS) and progression-free survival (PFS). For effect measure of complete remission rate (CRR), partial response rate (PRR), treatment-related mortality (TRM) and AEs we used risk ratios (RR). Two review authors (NB, NS) independently extracted data and assessed the quality of trials. Our search strategies led to 699 potentially relevant references. Of these, one RCT involving 79 patients was included. We judged the quality of the trial as moderate. The study was reported as a randomised open-label study and published as a full-text article.Even though PFS was statistically significantly improved for patients treated with HD-MTX plus cytarabine (HR 0.54; 95% CI 0.31 to 0.92; P = 0.01), this did not translate to a statistical significant OS benefit (HR 0.65; 95% CI 0.38 to 1.13; P = 0.07). AEs, especially infective complications, hepatotoxicity and haematological toxicities, were assessed more often in patients undergoing HD-MTX therapy combined with cytarabine. However, there were no statistically significant differences in terms of TRM (RR 3.08; 95% CI 0.33 to 28.32; P = 0.35). Owing to the small number of included trials and patients, the findings in this review remain uncertain. In summary, the presently available evidence (one small trial) showed a benefit in terms of PFS, ORR and CRR but no statistically significant difference regarding OS for patients with PCNSL treated with HD-MTX plus cytarabine compared to HD-MTX alone. However, the risk of severe infections and toxicity was significantly higher in patients treated with combined chemotherapy. More RCTs with additional chemotherapy to HD-MTX therapy with higher numbers of patients and longer follow-up periods are needed to confirm the results of this review and determine whether the PFS benefit will translate into an OS advantage. At least the one included study shows that RCTs of moderate quality and with valuable outcomes for this malignant disease are feasible.


Schaaf M.,University of Cologne
Cochrane database of systematic reviews (Online) | Year: 2012

Follicular lymphoma (FL) is the most common indolent and second most common Non-Hodgkin`s lymphoma (NHL) in the Western world. Standard treatment usually includes rituximab and chemotherapy. High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is an option for patients in advanced stages or for second-line therapy, leading to improved progression-free survival (PFS) rates. However, the impact of HDT and ASCT remains unclear, as there are hints of an increased risk of second cancers. We performed a systematic review with meta-analysis of randomised controlled trials (RCTs) comparing HDT plus ASCT with chemotherapy or immuno-chemotherapy in patients with FL with respect to overall survival (OS), PFS, treatment-related mortality (TRM), adverse events and secondary malignancies. We searched CENTRAL, MEDLINE, and EMBASE as well as conference proceedings from January 1985 to September 2011 for RCTs. Two review authors independently screened search results. Randomised controlled trials comparing chemotherapy or immuno-chemotherapy with HDT followed by ASCT in adults with previously untreated or relapsed FL. We used hazard ratios (HR) as effect measures used for OS and PFS as well as relative risks for response rates. Two review authors independently extracted data and assessed the quality of trials. Our search strategies led to 3046 potentially relevant references. Of these, five RCTs involving 1093 patients were included; four trials in previously untreated patients and one trial in relapsed patients. Overall, the quality of the five trials is judged to be moderate. All trials were reported as randomised and judged to be open-label studies, because usually trials evaluating stem cell transplantation are not blinded. Due to the small number of studies in each analysis (four or less), the quantification of heterogeneity was not reliable and not evaluated in further detail. A potential source of bias are uncertainties in the HR calculation. For OS, the HR had to be calculated for three trials from survival curves, for PFS for two trials.We found a statistically significant increased PFS in previously untreated FL patients in the HDT + ASCT arm (HR = 0.42 (95% confidence interval (CI) 0.33 to 0.54; P < 0.00001). However, this effect is not transferred into a statistically significant OS advantage (HR = 0.97; 95% 0.76 to 1.24; P = 0.81). The subgroup of trials adding rituximab to both intervention arms (one trial) confirms these results and the trial had to be stopped early after an interim analysis due to a statistically significant PFS advantage in the HDT + ASCT arm (PFS: HR = 0.36; 95% CI 0.23 to 0.55; OS: HR = 0.88; 95% CI 0.40 to 1.92). In the four trials in previously untreated patients there are no statistically significant differences between HDT + ASCT and the control-arm in terms of TRM (RR = 1.28; 95% CI 0.25 to 6.61; P = 0.77), secondary acute myeloid leukaemia/myelodysplastic syndromes (RR = 2.87; 95% CI 0.7 to 11.75; P = 0.14) or solid cancers (RR = 1.20; 95% CI 0.25 to 5.77; P = 0.82). Adverse events were rarely reported and were observed more frequently in patients undergoing HDT + ASCT (mostly infections and haematological toxicity).For patients with relapsed FL, there is some evidence (one trial, N = 70) that HDT + ASCT is advantageous in terms of PFS and OS (PFS: HR = 0.30; 95% CI 0.15 to 0.61; OS: HR = 0.40; 95% CI 0.18 to 0.89). For this trial, no results were reported for TRM, adverse events or secondary cancers. In summary, the currently available evidence suggests a strong PFS benefit for HDT + ASCT compared with chemotherapy or immuno-chemotherapy in previously untreated patients with FL. No statistically significant differences in terms of OS, TRM and secondary cancers were detected. These effects are confirmed in a subgroup analysis (one trial) adding rituximab to both treatment arms. Further trials evaluating this approach are needed to determine this effect more precisely in the era of rituximab. Moreover, longer follow-up data are necessary to find out whether the PFS advantage will translate into an OS advantage in previously untreated patients with FL.There is evidence that HDT + ASCT is advantageous in patients with relapsed FL.


Kiefer C.,University of Cologne
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2012

I describe how we can understand the classical appearance of our world from a universal quantum theory. The essential ingredient is the process of decoherence. I start with a general discussion in ordinary quantum theory and then turn to quantum gravity and quantum cosmology. There is a whole hierarchy of classicality from the global gravitational field to the fluctuations in the cosmic microwave background, which serve as the seeds for the structure in the Universe. © 2012 The Royal Society.


Tokano T.,University of Cologne
Icarus | Year: 2012

The impact of Titans large-scale topography and surface roughness on the atmospheric angular momentum budget is investigated by the Cologne Titan general circulation model that is run with and without topography constrained by Cassini. On seasonal timescales the angular momentum exchange is dominated by the friction torque, which oscillates semi-annually. Topography gives rise to a large diurnal and small seasonal mountain torque. The diurnal mountain torque is caused by surface pressure variations associated with Saturns tide, but has no net effect on the atmospheric angular momentum. The seasonal mountain torque is mainly contributed by low-latitude mountains that are hit by easterly surface winds. The seasonal mountain torque causes a net transfer of angular momentum from the surface to the atmosphere, which is counterbalanced by an opposite angular momentum transfer by the friction torque. The atmospheric angular momentum is larger if topography is included. © 2012 Elsevier Inc.


Allogeneic haematopoietic stem cell transplantation (HSCT) is an established treatment for many malignant and non-malignant haematological disorders. Graft-versus-host disease (GVHD), a condition frequently occurring after HSCT, is the result of host tissues being attacked by donor immune cells. One strategy for the prevention of GVHD is the administration of anti-thymocyte globulins (ATG), a set of polyclonal antibodies directed against a variety of immune cell epitopes, leading to immunosuppression and immunomodulation. To assess the effect of ATG used for the prevention of graft-versus-host disease (GVHD) in patients undergoing allogeneic HSCT with regard to overall survival, incidence and severity of acute and chronic GVHD, incidence of relapse, incidence of infectious complications, non-relapse mortality, early mortality within 100 days of transplantation, progression-free survival, quality of life and adverse events. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE (January 1950 to February 2012), trials registries and conference proceedings. The search was conducted in October 2010 and was updated in July 2011 and February 2012. We did not apply any language restrictions. We included randomised controlled trials (RCTs) investigating the impact of ATG on GVHD prophylaxis in adults suffering from haematological diseases and undergoing allogeneic HSCT. Treatment arms had to differ only in the addition of ATG to the standard GVHD prophylaxis regimen. Two review authors screened abstracts, extracted data and analysed the data independently. We contacted study authors for additional information. We included in the meta-analysis six RCTs which met the pre-defined selection criteria, involving a total of 568 participants. Quality of data reporting was heterogeneous among these studies with a lack of detailed information in the early studies.The primary outcome of overall survival was not significantly changed by the addition of ATG for the prophylaxis of GVHD (harms ratio (HR) 0.88; 95% CI 0.67 to 1.15, P = 0.33).The incidence of treatment-requiring or severe acute GVHD (grade II to IV) was significantly lower in patients who received ATG (risk ratio (RR) 0.68; 95% CI 0.55 to 0.85, P = 0.009; number needed to treat (NNT) 8). Also, the incidence of severe acute GVHD (grade III to IV) was significantly reduced (HR 0.53; 95% CI 0.33 to 0.85, P = 0.0005; NNT 7) but comparable data were available for rabbit ATG only. However, pooled study results regarding the incidence of acute GVHD of all grades (I to IV) showed no significant benefit of ATG treatment (RR 0.89; 95% CI 0.74 to 1.06, P = 0.20).Meta-analysis of data regarding the incidence of overall chronic GVHD (both, limited and extensive) was not possible. Nevertheless, studies reporting on extensive chronic GVHD (only studies evaluating rabbit ATG) suggested a lower incidence of extensive chronic GVHD whereas others that only reported on overall chronic GVHD did not show an advantage for ATG.Pooled results regarding the incidence of relapse were not significantly different (RR 1.13; 95% CI 0.75 to 1.68, P = 0.56), as well as pooled results regarding non-relapse mortality (HR 0.82; 95% CI 0.55 to 1.24, P = 0.35).Due to the lack of comparable data, we could not perform meta-analysis of data regarding the incidence of chronic GVHD, relapse-related mortality, progression-free survival, quality of life, adverse events and engraftment. Our systematic review suggests that the addition of ATG during allogeneic HSCT significantly reduces the incidence of severe grades (II to IV) of acute GvHD, whereas the incidence of overall acute GVHD (grades I to IV) was not significantly lowered. This indicates a reduction of the severity but not the incidence of acute GVHD. However, this effect did not lead to a significant improvement of overall survival, which may be due to the severe potential side effects of the consecutively increased immunosuppression.Furthermore, future research is needed to clarify the effect of ATG on the incidence and severity of chronic GVHD and consequently on all aspects of quality of life.From the currently available data, no recommendation on the general use of ATG in allogeneic HSCT can be supported. Therefore, a careful consideration of the use of ATG based on the patient's condition and the risk factors of the transplantation setting should be made.


Skoetz N.,University of Cologne
Cochrane database of systematic reviews (Online) | Year: 2012

Chronic lymphocytic leukaemia (CLL) accounts for 25% of all leukaemias and is the most common lymphoid malignancy in Western countries. Standard treatment  includes mono- or poly-chemotherapies. Nowadays, monoclonal antibodies are added, especially alemtuzumab and rituximab. However, the impact of these agents remains unclear, as there are hints of an increased risk of severe infections. To assess alemtuzumab compared with no further therapy, or with other anti-leukaemic therapy in patients with CLL. We searched CENTRAL and MEDLINE (from January 1985 to November 2011), and EMBASE (from 1990 to 2009) as well as conference proceedings for randomised controlled trials (RCTs). Two review authors (KB, NS) independently screened search results. We included RCTs comparing alemtuzumab with no further therapy or comparing alemtuzumab with anti-leukaemic therapy such as chemotherapy or monoclonal antibodies in patients with histologically-confirmed B-cell CLL. Both pretreated and chemotherapy-naive patients were included. We used hazard ratios (HR) as an effect measure for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) for response rates, treatment-related mortality (TRM) and adverse events. Two review authors independently extracted data and assessed the quality of trials. Our search strategies led to 1542 potentially relevant references. Of these, we included five RCTs involving 845 patients. Overall, we judged the quality of the five trials as moderate. All trials were reported as randomised and open-label studies. However, two trials were published as abstracts only, therefore, we were unable to assess the potential risk of bias for these trials in detail. Because of the small number of studies in each analysis (two), the quantification of heterogeneity was not reliable.Two trials (N = 356) assessed the efficacy of alemtuzumab compared with no further therapy. One trial (N = 335), reported a statistically significant OS advantage for all patients receiving alemtuzumab (HR 0.65 (95% confidence interval (CI) 0.45 to 0.94; P = 0.021). However, no improvement was seen for the subgroup of patients in Rai stage I or II (HR 1.07; 95% CI 0.62 to 1.84; P = 0.82). In both trials, the complete response rate (CRR) (RR 2.61; 95% CI 1.26 to 5.42; P = 0.01) and PFS (HR 0.58; 95% CI 0.44 to 0.76; P < 0.0001) were statistically significantly increased under therapy with alemtuzumab. The potential heterogeneity seen in the forest plot could be due to the different study designs: One trial evaluated alemtuzumab additional to fludarabine as relapse therapy; the other trial examined alemtuzumab compared with no further therapy for consolidation after first remission.There was no statistically significant difference for TRM between both arms (RR 0.57; 95% CI 0.17 to 1.90; P = 0.36). A statistically significant higher rate of CMV reactivation (RR 10.52; 95% CI 1.42 to 77.68; P = 0.02) and infections (RR 1.32; 95% CI 1.01 to 1.74; P = 0.04) occurred in patients receiving alemtuzumab. Seven severe infections (64%) in the alemtuzumab arm in the GCLLSG CLL4B study led to premature closure.Two trials (N = 177), evaluated alemtuzumab versus rituximab. Neither study reported OS or PFS. We could not detect a statistically significant difference for CRR (RR 0.85; 95% CI 0.67 to 1.08; P = 0.18) or TRM (RR 3.20; 95% CI 0.66 to 15.50; P = 0.15) between both arms. However, the CLL2007FMP trial was stopped early due to an increase in mortality in the alemtuzumab arm. More serious adverse events occurred in this arm (43% versus 22% (rituximab), P = 0.006).One trial (N = 297), assessed the efficacy of alemtuzumab compared with chemotherapy (chlorambucil). For this trial, no HR is reported for OS.


Pfister H.,University of Cologne
Journal of Investigative Dermatology | Year: 2015

In this issue, Genders et al. (2015) demonstrate in a cohort of organ transplant recipients that betapapillomavirus seropositivity around transplantation significantly increases the risk of developing keratinocyte carcinomas. These results further substantiate an etiologic role of betapapillomaviruses in skin cancer and raise prospects of anti-viral immunotherapy. © 2015 The Society for Investigative Dermatology.


Hofmann P.,University of Cologne | Wagner T.,Northumbria University
Paleoceanography | Year: 2011

This study presents high resolution organic and inorganic proxy records for Coniacian to Santonian black shale on the Demerara Rise (ODP Site 1261) in the western tropical Atlantic off South America. We integrate these records with approximately time equivalent geochemical data from the eastern tropical Atlantic off tropical Africa (ODP Site 959) to extract the underlying relationships of Intertropical Convergence Zone (ITCZ) dynamics and black shale formation in the tropical Cretaceous Atlantic at orbital time scales. The geochemical records from the Demerara Rise show repetitive fluctuations in productivity, ocean redox conditions, and clastic sediment supply consistent with a dynamic paleo-upwelling regime off tropical South America. Upwelling intensity most likely was driven by shifts of the mean annual position of the ITCZ, which connects the large-scale precipitation and wind field patterns of the Hadley cells. Upwelling was strongest off South America and burial of oil-prone organic matter most pronounced when the ITCZ was in its southernmost position, which maximized the impact of NE trade winds on the inner, tropical part of the northern Hadley cell. Geochemical records from the Deep Ivorian Basin (equatorial Atlantic) suggest that source rock formation occurred in phase with regions north of the equator. Off tropical Africa, however, black shale formation was primarily driven by regional rainfall and nutrient export. The results of this study provide a conceptual framework that explains the formation, distribution and quality of petroleum source rocks below the tropical component of the Hadley cells on orbital time scales. Copyright 2011 by the American Geophysical Union.


Antebi A.,Max Planck Institute for Biology of Ageing | Antebi A.,University of Cologne | Antebi A.,Baylor College of Medicine
Current Topics in Developmental Biology | Year: 2013

Hormones play a critical role in driving major stage transitions and developmental timing events in many species. In the nematode C. elegans the steroid hormone receptor, DAF-12, works at the confluence of pathways regulating developmental timing, stage specification, and longevity. DAF-12 couples environmental and physiologic signals to life history regulation, and it is embedded in a rich architecture governing diverse processes. Here, we highlight the molecular insights, extraordinary circuitry, and signaling pathways governing life stage transitions in the worm and how they have yielded fundamental insights into steroid regulation of biological time. © 2013 Elsevier Inc.


Maahn M.,University of Cologne | Kollias P.,McGill University
Atmospheric Measurement Techniques | Year: 2012

The Micro Rain Radar 2 (MRR) is a compact Frequency Modulated Continuous Wave (FMCW) system that operates at 24 GHz. The MRR is a low-cost, portable radar system that requires minimum supervision in the field. As such, the MRR is a frequently used radar system for conducting precipitation research. Current MRR drawbacks are the lack of a sophisticated post-processing algorithm to improve its sensitivity (currently at +3 dBz), spurious artefacts concerning radar receiver noise and the lack of high quality Doppler radar moments. Here we propose an improved processing method which is especially suited for snow observations and provides reliable values of effective reflectivity, Doppler velocity and spectral width. The proposed method is freely available on the web and features a noise removal based on recognition of the most significant peak. A dynamic dealiasing routine allows observations even if the Nyquist velocity range is exceeded. Collocated observations over 115 days of a MRR and a pulsed 35.2 GHz MIRA35 cloud radar show a very high agreement for the proposed method for snow, if reflectivities are larger than g-5 dBz. The overall sensitivity is increased to g-14 and g-8 dBz, depending on range. The proposed method exploits the full potential of MRR's hardware and substantially enhances the use of Micro Rain Radar for studies of solid precipitation. © 2012 Author(s).


Brocker J.,Max Planck Institute for the Physics of Complex Systems | Szendro I.G.,University of Cologne
Quarterly Journal of the Royal Meteorological Society | Year: 2012

Data assimilation refers to the problem of finding trajectories of a prescribed dynamical model in such a way that the output of the model (usually some function of the model states) follows a given time series of observations. Typically though, these two requirements cannot both be met at the same time-tracking the observations is not possible without the trajectory deviating from the proposed model equations, while adherence to the model requires deviations from the observations. Thus, data assimilation faces a trade-off. In this contribution, the sensitivity of the data assimilation with respect to perturbations in the observations is identified as the parameter which controls the trade-off. A relation between the sensitivity and the out-of-sample error is established, which allows the latter to be calculated under operational conditions. A minimum out-of-sample error is proposed as a criterion to set an appropriate sensitivity and to settle the discussed trade-off. Two approaches to data assimilation are considered, namely variational data assimilation and Newtonian nudging, also known as synchronization. Numerical examples demonstrate the feasibility of the approach. Copyright © 2011 Royal Meteorological Society.


Recent clinical trials with chimeric antigen receptor (CAR) redirected T cells targeting CD19 revealed particular efficacy in the treatment of leukemia/lymphoma, however, were accompanied by a lasting depletion of healthy B cells. We here explored CD30 as an alternative target, which is validated in lymphoma therapy and expressed by a broad variety of Hodgkin’s and non-Hodgkin’s lymphomas. As a safty concern, however, CD30 is also expressed by lymphocytes and hematopoietic stem and progenitor cells (HSPCs) during activation. We revealed that HRS3scFv-derived CAR T cells are superior since they were not blocked by soluble CD30 and did not attack CD30+ HSPCs while eliminating CD30+ lymphoma cells. Consequently, normal hemato- and lymphopoiesis was not affected in the long-term in the humanized mouse; the number of blood B and T cells remained unchanged. We provide evidence that the CD30+ HSPCs are protected against a CAR T-cell attack by substantially lower CD30 levels than lymphoma cells and higher levels of the granzyme B inactivating SP6/PI9 serine protease, which furthermore increased upon activation. Taken together, adoptive cell therapy with anti-CD30 CAR T cells displays a superior therapeutic index in the treatment of CD30+ malignancies leaving healthy activated lymphocytes and HSPCs unaffected.Molecular Therapy (2016); doi:10.1038/mt.2016.82. © 2016 American Society of Gene & Cell Therapy


Schilbach L.,University of Cologne
Frontiers in Human Neuroscience | Year: 2014

Social neuroscience studies the neurobiological underpinnings of people making sense of people. Due to both conceptual and methodological constraints, the majority of studies in this field of research, however, has employed experimental paradigms that focus on social cognition from an observer's rather than from an interactor's point of view (offline vs. online social cognition). This calls for an increased effort to systematically investigate the neural bases of participation in real-time social interaction. In light of the ontogenetic primacy of social interaction over observation and the idea that neural networks established during social interaction may be "re-used" during observation, other important objectives of the field will be to relate new findings into the neural bases of social interaction to previous work investigating the neural bases of social observation as well as to find ways to directly compare the two. © 2014 Schilbach.


Hinzen K.-G.,University of Cologne
Journal of Seismology | Year: 2012

Vertically oriented objects, such as tombstones, monuments, columns, and stone lanterns, are often observed to shift and rotate during earthquake ground motion. Such observations are usually limited to the mesoseismal zone. Whether near-field rotational ground motion components are necessary in addition to pure translational movements to explain the observed rotations is an open question. We summarize rotation data from seven earthquakes between 1925 and 2009 and perform analog and numeric rotation testing with vertically oriented objects. The free-rocking motion of a marble block on a sliding table is disturbed by a pulse in the direction orthogonal to the rocking motion. When the impulse is sufficiently strong and occurs at the 'right' moment, it induces significant rotation of the block. Numeric experiments of a free-rocking block show that the initiation of vertical block rotation by a cycloidal acceleration pulse applied orthogonal to the rocking axis depends on the amplitude of the pulse and its phase relation to the rocking cycle. Rotation occurs when the pulse acceleration exceeds the threshold necessary to provoke rocking of a resting block, and the rocking block approaches its equilibrium position. Experiments with blocks subjected to full 3D strong motion signals measured during the 2009 L'Aquila earthquake confirm the observations from the tests with analytic ground motions. Significant differences in the rotational behavior of a monolithic block and two stacked blocks exist. © 2011 Springer Science+Business Media B.V.


Brizuela D.,University of the Basque Country | Brizuela D.,University of Cologne
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

The classical and quantum evolution of a generic probability distribution is analyzed. To that end, a formalism based on the decomposition of the distribution in terms of its statistical moments is used, which makes explicit the differences between the classical and quantum dynamics. In particular, there are two different sources of quantum effects. Distributional effects, which are also present in the classical evolution of an extended distribution, are due to the fact that all moments cannot be vanishing because of the Heisenberg uncertainty principle. In addition, the noncommutativity of the basic quantum operators add some terms to the quantum equations of motion that explicitly depend on the Planck constant and are not present in the classical setting. These are thus purely quantum effects. Some particular Hamiltonians are analyzed that have very special properties regarding the evolution they generate in the classical and quantum sector. In addition, a large class of inequalities obeyed by high-order statistical moments, and in particular uncertainty relations that bound the information that is possible to obtain from a quantum system, are derived. © 2014 American Physical Society.


Masuda T.,University of Tokyo | Nishinari K.,University of Tokyo | Schadschneider A.,University of Cologne
Physical Review Letters | Year: 2014

We propose a simple microscopic model for arching phenomena at bottlenecks. The dynamics of particles in front of a bottleneck is described by a one-dimensional stochastic cellular automaton on a semicircular geometry. The model reproduces oscillation phenomena due to the formation and collapsing of arches. It predicts the existence of a critical bottleneck size for continuous particle flows. The dependence of the jamming probability on the system size is approximated by the Gompertz function. The analytical results are in good agreement with simulations. © 2014 American Physical Society.


Micklitz T.,Brazilian Center for Research in Physics (CBPF) | Muller C.A.,University of Konstanz | Muller C.A.,National University of Singapore | Altland A.,University of Cologne
Physical Review Letters | Year: 2014

Signatures of Anderson localization in the momentum distribution of a cold atom cloud after a quantum quench are studied. We consider a quasi-one-dimensional cloud initially prepared in a well-defined momentum state, and expanding for some time in a disorder speckle potential. Quantum interference generates a peak in the forward scattering amplitude which, unlike the common weak localization backscattering peak, is a signature of strong Anderson localization. We present a nonperturbative, and fully time resolved description of the phenomenon, covering the entire diffusion-to-localization crossover. Our results should be observable by present day experiments. © 2014 American Physical Society.


Hoberg K.,Kuehne Logistics University | Thonemann U.W.,University of Cologne
International Journal of Production Economics | Year: 2014

Advanced inventory policies require timely system-wide information on inventories and customer demand to accurately control the entire supply chain. However, the presence of unsynchronized processes, processing lags or inadequate communication structures hinder the widespread availability of real-time information. Therefore, inventory systems often have to deal with obsolete data which can seriously harm the overall supply chain performance. In this paper, we apply transfer function methods to analyze the effect of information delays on the performance of supply chains. We expose the common echelon-stock policy to information delays and determine to what extent a delay in inventory information and point-of-sale data deteriorates the inventory policies performance. We compare the performance of this policy with the performance of an installation-stock policy that is independent of information delays since it only requires local information. We find that this simple policy should be preferred in certain settings compared to relying on a complex policy with outdated system-wide information. We derive an echelon-stock policy that compensates for information delays and show that its performance improves significantly in their presence. We note potential applications of the approach in service parts supply chains, the hardwood supply chain, and in fast moving consumer goods settings. © 2014 Elsevier B.V.


Bramkamp M.,Ludwig Maximilians University of Munich | Bramkamp M.,University of Cologne
Biological Chemistry | Year: 2012

Membrane dynamics are essential for numerous cellular processes in eukaryotic and prokaryotic cells. In eukaryotic cells, membrane fusion and fission are often catalyzed by large GTPases of the dynamin protein family. These proteins couple GTP hydrolysis to membrane deformation, which eventually leads to fusion or fission of the lipid bilayer. Mutations in eukaryotic dynamin-like proteins (DLPs) are associated with various diseases underscoring the importance to fully understand the biochemistry of these proteins. In recent years, a wealth of structural and biochemical data have been published that allow a detailed analysis of how dynamins or DLPs modulate biological membranes. However, less is known about the function of bacterial DLPs, although structural data exist. This review summarizes current knowledge about bacterial dynamins and discusses structural and functional properties in comparison to their eukaryotic counterparts. © 2012 Walter de Gruyter GmbH, Berlin/Boston.


Chandler J.W.,University of Cologne
Cellular and Molecular Life Sciences | Year: 2012

Plant development and architecture is regulated by meristems that initiate lateral organs on their flanks. The gene regulatory networks that govern the transition of a vegetative shoot apical meristem into an inflorescence meristem (IM), together with those necessary to specify floral meristem (FM) identity have been elucidated in Arabidopsis thaliana and are highly complex and redundant. FMs are initiated in the axils of cryptic bracts and evidence suggests that FMs emerge and differentiate along an abaxial/adaxial axis, in contrast to existing models of centroradial positional information within FMs. Real-time imaging has revealed dynamic cell division and gene expression patterns associated with incipient primordia in the IM. This review, however, outlines how little is known concerning the identity of these primordia, the timing of FM specification and commitment in relation to the establishment of FM identity, and the interplay between bract and FM founder cell recruitment and development. © 2012 Springer Basel AG.


Malecki J.,University of British Columbia | Sela E.,University of Cologne | Affleck I.,University of British Columbia
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

The observation of the quantum critical point in a series double quantum dot system depends on the distinct separation of two scales, T K ≫ T *, where T K is the Kondo temperature and T * is the scale at which the system renormalizes away from the quantum critical point to a stable Fermi-liquid fixed point. Using the two-impurity Kondo model, we provide a derivation of T * based on the renormalization group (RG) to lowest order. This result is confirmed by a numerical RG (NRG) analysis which supplements the analytic derivation with additional quantitative precision. The form of the low-energy Fermi-liquid fixed point is derived and subsequently confirmed by the NRG. From this analysis, we conclude that the aforementioned separation of scales is satisfied, allowing the possibility that the quantum critical point may be measured in a future experiment on such double quantum dot systems. © 2010 The American Physical Society.


Plutzer J.,National Institute of Environmental Health | Ongerth J.,University of Wollongong | Karanis P.,University of Cologne
International Journal of Hygiene and Environmental Health | Year: 2010

Giardia duodenalis (synonymous Giardia lamblia and Giardia intestinalis) is a flagellated protozoan parasite that reproduces in the small intestine causing giardiasis. It is a cosmopolitan pathogen with a very wide host range, including domestic and wild animal species, as well as human beings. In this paper the current knowledge about the taxonomy and phylogeny of G. duodenalis is summarized from the international literature and data on the detection and epidemiology are also reviewed concentrating on the last 20 years. Authors highlighted the current knowledge and some aspects on G. duodenalis in particular, water transmission and in vitro cultivation. The review sheds light on the difficulties of the strain differentiation and multilocus molecular analysis of Giardia strains especially when applied to water samples containing low numbers of cysts and components complicating the problem of tracking sources of contamination. Genetic elements determining or conferring traits such as infectivity, pathogenicity, virulence, and immune interaction contributing to clearance are currently not well established, if at all. These should be useful and important topics for future research. © 2010 Elsevier GmbH.


Scaal M.,University of Cologne
Seminars in Cell and Developmental Biology | Year: 2016

The segmental organization of the vertebrate body is most obviously visible in the vertebral column, which consists of a series of vertebral bones and interconnecting joints and ligaments. During embryogenesis, the vertebral column derives from the somites, which are the primary segments of the embryonic paraxial mesoderm. Anatomical, cellular and molecular aspects of vertebral column development have been of interest to developmental biologists for more than 150 years. This review briefly summarizes the present knowledge on early steps of vertebral column development in amniotes, starting from sclerotome formation and leading to the establishment of the anatomical bauplan of the spine composed of vertebral bodies, vertebral arches, intervertebral discs and ribs, and their specific axial identities along the body axis. © 2015 Elsevier Ltd.


Nomura K.,University of Cologne | Rodriguez-Guzman R.,Rice University | Robledo L.M.,Autonomous University of Madrid
Physical Review C - Nuclear Physics | Year: 2013

The interacting boson model with configuration mixing, with parameters derived from the self-consistent mean-field calculation employing the microscopic Gogny energy density functional, is applied to the systematic analysis of the low-lying structure in Hg isotopes. Excitation energies, electromagnetic transition rates, deformation properties, and ground-state properties of the 172-204Hg nuclei are obtained by mapping the microscopic deformation energy surface onto the equivalent interacting boson model Hamiltonian in the boson condensate. These results point to the overall systematic trend of the transition from the near-spherical vibrational state in lower-mass Hg nuclei close to 172Hg, the onset of the intruder prolate configuration as well as the manifest prolate-oblate shape coexistence around the midshell nucleus 184Hg, and a weakly oblate deformed structure beyond 190Hg up to the spherical vibrational structure toward the near-semimagic nucleus 204Hg, as observed experimentally. The quality of the present method in the description of the complex shape dynamics in Hg isotopes is examined. © 2013 American Physical Society.


Rubbert-Roth A.,University of Cologne
Rheumatology (United Kingdom) | Year: 2012

Biologic treatments-including five TNF-α inhibitors, the IL-1 receptor antagonist anakinra, the IL-6 receptor inhibitor tocilizumab, the selective inhibitor of T-cell co-stimulation abatacept and the B-cell-directed mAb rituximab-have provided effective therapeutic options for patients with RA with inadequate response to conventional DMARDs. However, the fact that these agents are immune modulators has raised safety concerns, prompting careful evaluation in clinical trials and intensive post-marketing surveillance. Serious infections may arise, and diagnosis may be delayed by an atypical spectrum of signs and symptoms. Patients may experience reactivation of latent tuberculosis, hepatitis B or C or opportunistic infections. RA is a risk factor for cancer, and biologic therapy may modestly increase the risk of lymphoma and some solid tumours beyond background. During biologic therapy, demyelinating disorders of the CNS have been noted, and pre-existing disease manifestations may be aggravated. Hepatic transaminase levels may increase, although these elevations are usually mild to moderate, transient and without clinical consequence. Hyperlipidaemia, which is responsive to lipid-lowering therapy, may develop, and patients with congestive heart failure may experience symptom exacerbation. Safe use of biologic agents requires thorough risk assessment of potential candidates for treatment and careful monitoring during and after therapy. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Hartwig B.,Max Planck Institute for Plant Breeding Research | James G.V.,Max Planck Institute for Plant Breeding Research | Konrad K.,University of Cologne | Schneeberger K.,Max Planck Institute for Plant Breeding Research | Turck F.,Max Planck Institute for Plant Breeding Research
Plant Physiology | Year: 2012

Mapping-by-sequencing (or SHOREmapping) has revitalized the powerful concept of forward genetic screens in plants. However, as in conventional genetic mapping approaches, mapping-by-sequencing requires phenotyping of mapping populations established from crosses between two diverged accessions. In addition to the segregation of the focal phenotype, this introduces natural phenotypic variation, which can interfere with the recognition of quantitative phenotypes. Here, we demonstrate how mapping-by-sequencing and candidate gene identification can be performed within the same genetic background using only mutagen-induced changes as segregating markers. Using a previously unknown suppressor of mutants of like heterochromatin protein1 (lhp1), which in its functional form is involved in chromatin-mediated gene repression, we identified three closely linked ethyl methanesulfonate-induced changes as putative candidates. In order to assess allele frequency differences between such closely linked mutations, we introduced deep candidate resequencing using the new Ion Torrent Personal Genome Machine sequencing platform to our mutant identification pipeline and thereby reduced the number of causal candidate mutations to only one. Genetic analysis of two independent additional alleles confirmed that this mutation was causal for the suppression of lhp1. © 2012 American Society of Plant Biologists. All Rights Reserved.


Wood W.,University of Bath | Eming S.A.,University of Cologne
EMBO Reports | Year: 2012

The fourth EMBO conference on 'The Molecular and Cellular Basis of Regeneration and Repair', held in September 2012, brought together researchers from both the regeneration and wound-healing fields. The meeting spanned a wide range of research topics from basic science to clinical application, and a veritable melting pot of model organisms and approaches resulted in an excellent fourth conference in this series. © 2012 European Molecular Biology Organization.


Steinwachs C.F.,University of Cologne | Kamenshchik A.Y.,National Institute of Nuclear Physics, Italy | Kamenshchik A.Y.,Russian Academy of Sciences
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2011

Using the generalized Schwinger-DeWitt technique, we calculate the divergent part of the one-loop effective action for gravity nonminimally coupled to a multiplet of scalar fields. All the calculations are consistently done in the Jordan frame. © 2011 American Physical Society.


Hecking H.,University of Cologne
Oxford Review of Economic Policy | Year: 2016

The paper investigates how a carbon price could halt the comeback of coal, which started in the early 2000s. Since the year 2000, coal has provided roughly 40 per cent of global primary energy growth. The success of coal in the primary energy mix is due to the fact that it is abundant, cheap, and most often a domestic resource. However, global coal reserves, if burnt, would surpass the remaining carbon budget for a 2°C target by a factor of two. The paper shows that a carbon price of 25-100 USD per tonne of CO2 would be needed to phase out coal in the power sector, depending on the technology and the world region, even when assuming significant technological progress. © The Author 2016. Published by Oxford University Press.


Rothenberger A.,University of Gottingen | Dopfner M.,University of Cologne
European Child and Adolescent Psychiatry | Year: 2011

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomized controlled trials as these are usually only shortterm. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPHMR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence. © 2011 The Author(s).


Fun A.,University Utrecht | Wensing A.M.J.,University Utrecht | Verheyen J.,University of Cologne | Nijhuis M.,University Utrecht
Retrovirology | Year: 2012

Human Immunodeficiency Virus (HIV) maturation plays an essential role in the viral life cycle by enabling the generation of mature infectious virus particles through proteolytic processing of the viral Gag and GagPol precursor proteins. An impaired polyprotein processing results in the production of non-infectious virus particles. Consequently, particle maturation is an excellent drug target as exemplified by inhibitors specifically targeting the viral protease (protease inhibitors; PIs) and the experimental class of maturation inhibitors that target the precursor Gag and GagPol polyproteins. Considering the different target sites of the two drug classes, direct cross-resistance may seem unlikely. However, coevolution of protease and its substrate Gag during PI exposure has been observed both in vivo and in vitro. This review addresses in detail all mutations in Gag that are selected under PI pressure. We evaluate how polymorphisms and mutations in Gag affect PI therapy, an aspect of PI resistance that is currently not included in standard genotypic PI resistance testing. In addition, we consider the consequences of Gag mutations for the development and positioning of future maturation inhibitors. © 2012 Fun et al.; licensee BioMed Central Ltd.


Niefind K.,University of Cologne | Issinger O.-G.,University of Southern Denmark
Biochimica et Biophysica Acta - Proteins and Proteomics | Year: 2010

At the first glance CK2α, the catalytic subunit of protein kinase CK2, is a rigid molecule: in contrast to many eukaryotic protein kinases in CK2α the canonical regulatory key elements like the activation segment occur exclusively in their typical active conformations. This observation fits well to the constitutive activity of the enzyme, meaning, its independence from phosphorylation or other characteristic control factors. Most CK2α structures are based on the enzyme from Zea mays, supplemented by an increasing number of human CK2α structures. In the latter a surprising plasticity of important ATP-binding elements - the interdomain hinge region and the glycine-rich loop - was discovered. In fully active CK2α the hinge region is open and does not anchor the ATP ribose, but alternatively it can adopt a closed conformation, form hydrogen bonds to the ribose moiety and thus retract the γ-phospho group from its functional position. In addition to this partially inactive state human CK2α was recently found in a fully inactive conformation. It is incompatible with ATP-binding due to a combination of a closed hinge and a collapse of the glycine-rich loop into the ATP cavity. These conformational transitions are apparently correlated with the occupation state of a remote docking site located at the interface to the non-catalytic subunit CK2β: if CK2β blocks this site, the fully active conformation of CK2α is stabilized, while the binding of certain small molecule seems to favour the partially and fully inactive states. This observation may be exploited to design effective and selective CK2 inhibitors. © 2009 Elsevier B.V. All rights reserved.


Cejnar P.,Charles University | Jolie J.,University of Cologne | Casten R.F.,Yale University
Reviews of Modern Physics | Year: 2010

Signatures of criticality in the evolution of the nuclear ground-state shapes across the N×Z plane are discussed. Attention is paid to specific data indicating sudden structural changes in various isotopic and isotonic chains of medium-mass and heavy even-even nuclei, as well as to diverse theoretical aspects of the models used to describe these changes. The interacting boson model and the geometric collective model, in particular, are discussed in detail, the former providing global predictions for the evolution of collective observables in nuclei between closed shells and the latter yielding a parameter-efficient description of nuclei at the critical points of shape transitions. Some issues related to the mechanism of first- and second-order quantum phase transitions in general many-body systems are also outlined. © 2010 The American Physical Society.


Based on a comprehensive computerized literature search supplemented by a specific manual search of the literature, the present review article focuses on concrete aspects of the application of surface electromyography (EMG) for evaluation of the masticatory muscles in general and of the masseter and anterior temporal muscles in particular, and presents the current base of knowledge on the clinical relevance of surface EMG in dental applications. In the first stage of the review, publications from the year 2000 or later reporting the results of controlled clinical trials (randomized as far as available) of patients with craniomandibular or temporomandibular disorders (TMD) were analyzed. Data from the selected publications were systematically compiled and divided into subject areas as follows: Resting activity, maximal and sub-maximal voluntary contraction, symmetry of EMG activity, and fatigue effects; EMG activity during mastication, factors (including pain) that affect EMG activity, and the impact of adjusting static and dynamic occlusal relationships; Effects of occlusal splints and other occlusal treatments. Surface electromyography is in principle a suitable tool for neuromuscular function analysis in the field of dentistry. If used according to the specific recommendations and in conjunction with a thorough and conscientious clinical history and physical examination, surface EMG measurements can provide objective, documentable, valid, and reproducible data on the functional condition of the masticatory muscles of an individual patient.


Popkov V.,University of Cologne | Popkov V.,University of Florence | Prosen T.,University of Ljubljana
Physical Review Letters | Year: 2015

We report a two-parametric irreducible infinitely dimensional representation of the Lax integrability condition for the Fermi Hubbard chain. In addition to being of fundamental interest, hinting at possible novel quantum symmetry of the model, our construction allows for an explicit representation of an exact steady state many-body density operator for a nonequilibrium boundary-driven Hubbard chain with arbitrary (asymmetric) particle source (sink) rates at the left (right) end of the chain and with arbitrary boundary values of chemical potentials. © 2015 American Physical Society.


Chandler J.W.,University of Cologne
Plant, Cell and Environment | Year: 2016

Auxin signalling involves the activation or repression of gene expression by a class of auxin response factor (ARF) proteins that bind to auxin response elements in auxin-responsive gene promoters. The release of ARF repression in the presence of auxin by the degradation of their cognate auxin/indole-3-acetic acid repressors forms a paradigm of transcriptional response to auxin. However, this mechanism only applies to activating ARFs, and further layers of complexity of ARF function and regulation are being revealed, which partly reflect their highly modular domain structure. This review summarizes our knowledge concerning ARF binding site specificity, homodimer and heterodimer multimeric ARF association and cooperative function and how activator ARFs activate target genes via chromatin remodelling and evolutionary information derived from phylogenetic comparisons from ARFs from diverse species. ARFs are regulated in diverse ways, and their importance in non-auxin-regulated pathways is becoming evident. They are also embedded within higher-order transcription factor complexes that integrate signalling pathways from other hormones and in response to the environment. The ways in which new information concerning ARFs on many levels is causing a revision of existing paradigms of auxin response are discussed. © 2015 John Wiley & Sons Ltd.


Hunzelmann N.,University of Cologne | Brinckmann J.,University of Lubeck
Annals of the Rheumatic Diseases | Year: 2010

Systemic sclerosis (SSc) is a chronic inflammatory autoimmune disease involving the connective tissue of the skin and various internal organs. In recent years research on SSc has evolved to provide a better understanding of the interdependence of the three major systems involved-namely, the vascular system, the immune system and the connective tissue. Hypoxia is increasingly recognised as a decisive factor in modulating the inflammatory process in SSc, activating fibroblasts and changing their phenotype. In addition, several mediators synthesised by immune cells, including cytokines such as transforming growth factor β (TGFβ) and platelet-derived growth factor (PDGF), cooperate in inducing the activation of fibroblasts and their differentiation into myofibroblasts. Therefore, a variety of intracellular and extracellular strategies to inhibit the activity of TGFβ and PDGF are currently receiving intense investigation. To further improve our therapeutic strategies for this paradigmatic fibrotic disease, an improved understanding of connective tissue remodelling as it takes place in the different stages of SSc will be imperative.


The IMPROVE-IT study has demonstrated a significant reduction of LDL-C when ezetimibe was given in addition to statins. Although the number of strokes and MI was reduced after 7 to 10 years of this treatment, mortality was unaffected, however. Additive ezetimibe treatment can be recommended only, if a better or longer life has been proved - which is not the case. © Georg Thieme Verlag KG Stuttgart New York.


This study aimed to assess the frequency of and the contributing factors for second primary malignancies (SPMs) and Richter’s transformations (RTs) following first-line treatment of chronic lymphocytic leukemia within four phase II/III trials of the GCLLSG evaluating fludarabine (F) vs F+cyclophosphamide (FC), chlorambucil vs F, FC without or with rituximab, and bendamustine+R (BR). Among 1458 patients, 239 (16.4%) experienced either an SPM (N=191) or a RT (N=75). Solid tumors (N=115; 43.2% of all second neoplasias) appeared most frequently, followed by RTs (N=75; 28.2%). Patients showed a 1.23-fold increased risk of solid tumors in comparison to the age-matched general population from the German cancer registry. Age>65 (hazard ratio (HR) 2.1; P<0.001), male sex (HR 1.7; P=0.01), co-morbidities (HR 1.6; P=0.01) and number of subsequent treatments⩾1 (HR 12.1; P<0.001) showed an independent adverse prognostic impact on SPM-free survival. Serum thymidine kinase>10 U/l at trial enrollment (HR 3.9; P=0.02), non-response to first-line treatment (HR 3.6; P<0.001) and number of subsequent treatments⩾1 (HR 30.2; P<0.001) were independently associated with increased risk for RT.Leukemia advance online publication, 27 May 2016; doi:10.1038/leu.2016.113. © 2016 Macmillan Publishers Limited


Picker S.M.,University of Cologne
Transfusion and Apheresis Science | Year: 2011

Platelets (PLTs), play a key role in hemostasis, clot stability and retraction as well as in vascular repair and anti-microbial host defense. Upon vessel wall damage, PLTs undergo a highly regulated set including adhesion, spreading, aggregation, release reactions as well as exposure of procoagulant surfaces to rapidly form a hemostatic plug that occludes the site of damage. When PLT function is impaired, the bleeding risk increases, but (hyperreactive) PLTs are also involved in many pathophysiological events like thrombosis, vessel constriction, atherogenesis, tumor growth and metastasis, inflammation including atherosclerosis and the subsequent formation of arterial thrombi resulting in stroke and myocardial infarction.While hereditary PLT function disorders are very rare, acquired PLT function abnormalities occur in the course of many diseases and can be associated with many drugs, i.e., non-steroidal anti-inflammatorics, antibiotics or heparin. Therefore, apart from disease diagnosis, severity, and prognosis, assessment of PLT function also serves for identifying the efficacy of anti-PLT therapy and PLT hyperfunction as a possible predictor for thromboembolic events. Since PLTs undergo a lot of measurable changes during storage ex-vivo, one effort of transfusion medicine is the quality monitoring of PLT concentrates (PCs), but also the detection of donors with PLT dysfunction and the determination of patients in which PLT transfusions are effective.The majority of PLT tests focus only on PLT functions involved directly in hemostasis including adhesion/aggregation, coagulation, and clot retraction. Traditional tests, almost complex, time-consuming, and poorly specified, are meanwhile enriched by more user friendly and easy-to-use point-of-care tests on fully automated instruments within whole blood without the requirement of sample processing. These tests help identifying surgical patients at increased risk of post-operative bleeding or with resistance to anti-PLT therapy, therefore at increased risk of thromboembolism. However, up to now, no study shows real outcome benefits by including these tests into the disease management. To date, no function test is suitable to address all distinct steps of PLT activation or reliably predict PLT behavior in vivo following transfusion. © 2011 Elsevier Ltd.


Gordon J.-S.,University of Cologne
Kennedy Institute of Ethics Journal | Year: 2011

This article examines the special relation between common morality and particular moralities in the four-principles approach and its use for global ethics. It is argued that the special dialectical relation between common morality and particular moralities is the key to bridging the gap between ethical universalism and relativism. The four-principles approach is a good model for a global bioethics by virtue of its ability to mediate successfully between universal demands and cultural diversity. The principle of autonomy (i.e., the idea of individual informed consent), however, does need to be revised so as to make it compatible with alternatives such as family- or community-informed consent. The upshot is that the contribution of the four-principles approach to global ethics lies in the so-called dialectical process and its power to deal with cross-cultural issues against the background of universal demands by joining them together. © 2011 by The Johns Hopkins University Press.


Organ-transplant-recipients exhibit cancerization of the skin from which multiple human papillomavirus (HPV)-positive squamous cell carcinomas (SCCs) arise. However, the molecular basis for HPV-induced invasion of skin keratinocytes is not known. We generated a transgenic mouse model expressing the E7 oncoprotein of HPV8 in the murine epidermis under the control of the keratin-14 promoter and showed that E7 is carcinogenic in mice. We further showed that both, the E7-expressing keratinocyte and mesenchymal components of the extracellular matrix as critical in eliciting the invasive behavior. E7 expression in basal keratinocytes, grown on fibronectin, led to epithelial–mesenchymal transition mediated by a cadherin switch. E7-positive keratinocytes displayed enhanced EDA-fibronectin expression and secretion and stimulated dermal fibroblasts to express EDA-fibronectin. Deposition of fibronectin was also detected in the peritumoral stroma of HPV8-positive skin SCC. When grown on fibronectin, E7-positive keratinocytes, in particular stem cell-like cells, exhibited increased cell surface levels of the α3-integrin chain. Functional blocking confirmed α3 as a critical molecule sufficient to induce E7-mediated invasion. This mechanistic link is further supported by expression of an E7-mutant, impaired in targeting α3 to the cell surface. These findings highlight the importance of epithelial–extracellular matrix interaction required for keratinocyte invasion and provide further mechanistic evidence for a role of HPV in skin carcinogenesis.Oncogene advance online publication, 25 January 2016; doi:10.1038/onc.2015.512. © 2016 Macmillan Publishers Limited