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Leipzig, Germany

Leipzig University , located in Leipzig in the Free State of Saxony, Germany, is one of the oldest universities in the world and the second-oldest university in Germany. Famous alumni include Leibniz, Goethe, Ranke, Nietzsche, Wagner, Angela Merkel, Raila Odinga, Tycho Brahe and nine Nobel laureates are associated with this university.The university was founded on December 2, 1409 by Frederick I, Elector of Saxony and his brother William II, Margrave of Meissen, and originally comprised the four scholastic faculties. Since its inception the university has engaged in teaching and research for over 600 years without interruption. Wikipedia.


Renner R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Seikowski K.,University of Leipzig
Acta Dermato-Venereologica | Year: 2014

Pain is a ubiquitous problem in patients with chronic leg wounds. The pain may be caused by the underlying pathology of the leg ulceration, the wound, wound treatment, or complications such as skin irritation around the ulcer. The objectives of this research were to evaluate the level of suffering endured by patients because of their ulcer-related pain, and to evaluate whether and how this pain is treated. In addition, to determine whether this pain influences quality of life and health status. In 2010, data were collected in order to characterize the patients by socio-demographic facts, such as age, gender, co-morbidity, pathogenesis of the wound, wound status of new patients, wound pain, and use of analgesics. In addition, modified EQ-5D questionnaires were distributed with additional questions concerning pain experience, treatment, and general health status. Of 103 patients, 45 were male and 58 female. Mean age was 67.8 years (males 65 years, females 70 years). Up to 69% had leg ulcerations due to vascular disease. Out of the 103 distributed questionnaires, 49 were returned and evaluated. Analysis showed that 82% of these patients reported wound-related pain, and 42% estimated their analgesics as not sufficiently pain relieving (mean value of the visual analogue scale (VAS) 4.9). Mean health status was 50.5 (maximal health status 100). Patients with a pain value ≥ 5 showed a lesser mean health status (42.2) than patients with a pain value < 5 (60.3). The proportion of patients receiving no, or only weak, analgesics was nearly the same for patients with VAS ≥ 5 and with VAS < 5. Further research in pain therapy is of utmost importance to improve the quality of life of patients with chronic wounds. © 2014 The Authors.


Goller S.,University of Bremen | Lohrey M.,University of Leipzig
SIAM Journal on Computing | Year: 2013

One-counter automata (OCA) are pushdown automata which operate only on a unary stack alphabet. We study the computational complexity of model checking computation tree logic (CTL) on transition systems induced by OCA. A PSPACE upper bound is inherited from the modal μ-calculus for this problem proved by Serre. First, we analyze the periodic behavior of CTL over OCA and derive a model checking algorithm whose running time is exponential only in the number of control locations and a syntactic notion of the formula that we call leftward until depth. In particular, model checking fixed OCA against CTL formulas with a fixed leftward until depth is in P. This generalizes a corresponding recent result of Göller, Mayr, and To for the expression complexity of CTL's fragment EF. Second, we prove that already over some fixed OCA, CTL model checking is PSPACE-hard, i.e., expression complexity is PSPACE-hard. Third, we show that there already exists a fixed CTL formula for which model checking of OCA is PSPACE-hard, i.e., data complexity is PSPACE-hard as well. To obtain the latter result, we employ two results from complexity theory: (i) Converting a natural number in Chinese remainder presentation into binary presentation is in logspace-uniform NC1 and (ii) PSPACE is AC0-serializable. We demonstrate that our approach can be used to obtain further results. We show that model checking CTL's fragment EF over OCA is hard for PNP, thus establishing a matching lower bound. Moreover, we show that the following problem is hard for PSPACE: Given a one-counter Markov decision process, a set of target states with counter value zero each, and an initial state, to decide whether the probability that the initial state will eventually reach one of the target states is arbitrarily close to 1. This improves a recently proved lower bound for every level of the boolean hierarchy shown by Brázdil et al. Finally, we prove that there is a fixed CTL formula for which model checking 2-clock timed automata is PSPACE-hard, generalizing a PSPACE-hardness result for the combined complexity by Laroussinie, Markey, and Schnoebelen. © 2013 Society for Industrial and Applied Mathematics.


Borries C.,German Aerospace Center | Hoffmann P.,University of Leipzig
Journal of Geophysical Research: Space Physics | Year: 2010

A first description of the characteristics of the F2-layer ionosphere oscillations with periods between 2 and 30 days (so-called planetary wave-type oscillations, PWTO) is derived using regional maps of total electron content (TEC), covering the northern hemisphere from 50°N to the North Pole. Oscillations forced by quasiperiodic variations of solar signals (e.g., extreme ultraviolet irradiation and solar wind) are identified and separated using wavelet transformation. It is found that up to 50% of the PWTO intensity in the F2-layer ionosphere occur due to solar variability. The signals that are not obviously related to solar variability are spectrally decomposed to characterize oscillations by their period and wave number. Climatological analyses of the occurring oscillations in TEC reveal similarities to stratospheric planetary waves (PW). These are typical periods of PW, the strongest wave activity during winter and the enhancement of the wave activity at similar latitudes. But there are also major differences to stratospheric PW. In the ionosphere zonal mean oscillations are dominant, stationary waves are not observed, and the dominant periods are shorter than the typical periods of PW in the stratosphere. However, the obtained results are in good agreement with recent numerical modeling results that showed no stationary wave propagation into the F2-region ionosphere and only fast, short-period waves that propagate up to the lower thermosphere. © 2010 by the American Geophysical Union.


Pfefferle D.,Max Planck Institute for Evolutionary Anthropology | Pfefferle D.,University of Leipzig | Pfefferle D.,University of Puerto Rico at San Juan
Proceedings. Biological sciences / The Royal Society | Year: 2014

Widespread evidence exists that when relatives live together, kinship plays a central role in shaping the evolution of social behaviour. Previous studies showed that female rhesus macaques (Macaca mulatta) recognize familiar maternal kin using vocal cues. Recognizing paternal kin might, however, be more difficult as rhesus females mate promiscuously during the possible conception period, most probably concealing paternity. Behavioural observations indicate that semi free-ranging female rhesus macaques prefer to associate with their paternal half-sisters in comparison to unrelated females within the same group, particularly when born within the same age cohort. However, the cues and mechanism/s used in paternal kin discrimination remain under debate. Here, we investigated whether female rhesus macaques use the acoustic modality to discriminate between paternal half-sisters and non-kin, and tested familiarity and phenotype matching as the underlying mechanisms. We found that test females responded more often to calls of paternal half-sisters compared with calls of unrelated females, and that this discrimination ability was independent of the level of familiarity between callers and test females, which provides, to our knowledge, the first evidence for acoustic phenotype matching. Our study strengthens the evidence that female rhesus macaques can recognize their paternal kin, and that vocalizations are used as a cue.


Hirrlinger J.,Max Planck Institute for Experimental Medicine | Hirrlinger J.,University of Leipzig | Hirrlinger J.,Carl Ludwig Institute for Physiology | Nave K.-A.,Max Planck Institute for Experimental Medicine
GLIA | Year: 2014

In the mammalian brain, the subcortical white matter comprises long-range axonal projections and their associated glial cells. Here, astrocytes and oligodendrocytes serve specific functions during development and throughout adult life, when they meet the metabolic needs of long fiber tracts. Within a short period of time, oligodendrocytes generate large amount of lipids, such as cholesterol, and membrane proteins for building the myelin sheaths. After myelination has been completed, a remaining function of glial metabolism is the energetic support of axonal transport and impulse propagation. Astrocytes can support axonal energy metabolism under low glucose conditions by the degradation of stored glycogen. Recently it has been recognized that the ability of glycolytic oligodendrocytes to deliver pyruvate and lactate is critical for axonal functions in vivo. In this review, we discuss the specific demands of oligodendrocytes during myelination and potential routes of metabolites between glial cells and myelinated axons. As examples, four specific metabolites are highlighted (cholesterol, glycogen, lactate, and N-acetyl-aspartate) that contribute to the specific functions of white matter glia. Regulatory processes are discussed that could be involved in coordinating metabolic adaptations and in providing feedback information about metabolic states. © 2014 Wiley Periodicals, Inc.


Kubus P.,Childrens Heart Center | Vit P.,Childrens University Hospital Brno | Gebauer R.A.,University of Leipzig | Materna O.,Childrens Heart Center | Janousek J.,Childrens Heart Center
Circulation: Arrhythmia and Electrophysiology | Year: 2014

Background-Data on the results and clinical effect of an invasive risk stratification strategy in asymptomatic young patients with the Wolff-Parkinson-White electrocardiographic pattern are scarce. Methods and Results-Eighty-five consecutive patients aged <18 years with a Wolff-Parkinson-White pattern and persistent preexcitation at maximum exercise undergoing invasive risk stratification were retrospectively studied. Adverse accessory pathway (AP) properties were defined according to currently consented criteria as any of the following: shortest preexcited RR interval during atrial fibrillation/rapid atrial pacing =250 ms (or antegrade effective refractory period =250 ms if shortest preexcited RR interval was not available) or inducible atrioventricular re-entrant tachycardia. Age at evaluation was median 14.9 years. Eighty-two patients had a structurally normal heart and 3 had hypertrophic cardiomyopathy. A single manifest AP was present in 80, 1 manifest and 1 concealed AP in 4, and 2 manifest APs in 1 patient. Adverse AP properties were present in 32 of 85 patients (37.6%) at baseline and in additional 16 of 44 (36.4%) after isoproterenol. Ablation was performed in 41 of these 48 patients. Ablation was deferred in the remaining 7 for pathway proximity to the atrioventricular node. In addition, 18 of the low-risk patients were ablated based on patient/parental decision. Conclusions-Adverse AP properties at baseline were exhibited by 37.6% of the evaluated patients with an asymptomatic Wolff-Parkinson-White preexcitation persisting at peak exercise. Isoproterenol challenge yielded additional 36.4% of those tested at higher risk. Ablation was performed in a total of 69.4% of patients subjected to invasive risk stratification. © 2014 American Heart Association, Inc.


Koch M.,Yale University | Koch M.,University of Leipzig | Horvath T.L.,Yale University
Molecular Psychiatry | Year: 2014

The brain receives and integrates environmental and metabolic information, transforms these signals into adequate neuronal circuit activities, and generates physiological behaviors to promote energy homeostasis. The responsible neuronal circuitries show lifetime plasticity and guaranty metabolic health and survival. However, this highly evolved organization has become challenged nowadays by chronic overload with nutrients and reduced physical activity, which results in an ever-increasing number of obese individuals worldwide. Research within the last two decades has aimed to decipher the responsible molecular and cellular mechanisms for regulation of the hypothalamic melanocortin neurons, which have a key role in the control of food intake and energy metabolism. This review maps the central connections of the melanocortin system and highlights its global position and divergent character in physiological and pathological metabolic events. Moreover, recently uncovered molecular and cellular processes in hypothalamic neurons and glial cells that drive plastic morphological and physiological changes in these cells, and account for regulation of food intake and energy metabolism, are brought into focus. Finally, potential functional interactions between metabolic disorders and psychiatric diseases are discussed. © 2014 Macmillan Publishers Limited All rights reserved.


Bluher M.,University of Leipzig
Internist | Year: 2014

The incidence of obesity has increased dramatically during recent decades. Obesity increases the risk for metabolic and cardiovascular diseases and may therefore contribute to premature death. With increasing fat mass, secretion of adipose tissue derived bioactive molecules (adipokines) changes towards a proinflammatory, diabetogenic and atherogenic pattern. Adipokines are involved in the regulation of appetite and satiety, energy expenditure, activity, endothelial function, hemostasis, blood pressure, insulin sensitivity, energy metabolism in insulin sensitive tissues, adipogenesis, fat distribution and insulin secretion in pancreatic β-cells. Therefore, adipokines are clinically relevant as biomarkers for fat distribution, adipose tissue function, liver fat content, insulin sensitivity and chronic inflammation and have the potential for future pharmacological treatment strategies for obesity and related diseases. This review focuses on the clinical relevance of selected adipokines as markers or predictors of obesity-related diseases and as potential therapeutic tools or targets in metabolic and cardiovascular diseases. © 2014 Springer-Verlag.


Preuss M.,University of Leipzig
Medical Hypotheses | Year: 2012

Brain edema concepts comprised interstitial, cytotoxic and vasogenic edema as three separate concepts. This is a theory of initiation of brain edema genesis arising from the neuron's cellular metabolism on the basis of energy failure by relative hyperglycolysis and resulting lactacidosis. It can describe edema genesis in trauma, hemorrhage, stroke and infections. © 2012 Elsevier Ltd.


Claussen I.,University of Gottingen | Mayr S.G.,University of Leipzig
New Journal of Physics | Year: 2011

We report on vibrating reed measurements combined with density functional theory-based calculations to assess the elastic and damping properties of Fe-Pd ferromagnetic shape memory alloy splats. While the austenite-martensite phase transformation is generally accompanied by lattice softening, a severe modulus defect and elevated damping behavior are characteristic of the martensitic state. We interpret the latter in terms of twin boundary motion between pinning defects via partial 'twinning' dislocations. Energy dissipation is governed by twin boundary drag, primarily due to lattice imperfections, as concluded from the temperature dependence of damping and related activation enthalpies. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Schakel A.M.J.,University of Leipzig | Schakel A.M.J.,Federal University of Pernambuco
Annals of Physics | Year: 2011

The effective action describing the gapless Nambu-Goldstone, or Anderson-Bogoliubov, mode of a zero-temperature dilute Fermi gas at unitarity is derived up to next-to-leading order in derivatives from the microscopic theory. Apart from a next-to-leading order term that is suppressed in the BCS limit, the effective action obtained in the strong-coupling unitary limit is proportional to that obtained in the weak-coupling BCS limit. © 2010 Elsevier Inc.


Hartwigsen G.,University of Leipzig | Siebner H.R.,Copenhagen University
Aphasiology | Year: 2012

Background: Current models emphasize that language-related functions are predominantly organized in left-lateralized fronto-temporo-parietal cortical networks.Aims: In this review, we summarize how "online" transcranial magnetic stimulation (TMS) during a language task can be used in healthy individuals to characterize the contribution of the stimulated area to a specific language function with a focus on the functional relevance of the right hemisphere. We first give an introduction to some basic mechanisms of TMS and outline the prerequisites for carrying out TMS studies of language. In particular, we highlight some methodological limitations and pitfalls of the TMS approach. We then review online TMS studies of language processing with a particular focus on the contribution of right hemisphere brain regions to language processing.Main Contribution: The majority of TMS studies on language have targeted a single left- hemisphere cortical area during a language task to identify the relevance of that area for a specific aspect of language processing. TMS has also been used to characterize the involvement of homologous right hemisphere regions. These studies have provided evidence for a significant role of right hemisphere regions in different aspects of language processing, including word comprehension, reading and paralinguistic features like emotional prosody.Conclusions: Recently, two areas have been targeted simultaneously with TMS while subjects performed a language task. This multifocal TMS approach has opened up new possibilities to compare the functional involvement of homologous regions in the right and left hemisphere and allows for the characterization of interhemispheric compensation during language processing. © 2012 Copyright 2012 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business.


Thiele H.,University of Leipzig
Deutsche Medizinische Wochenschrift | Year: 2013

This review will address the pathophysiology, incidence, current outcome and treatment options of patients with cardiogenic shock complicating acute myocardial infarction. The major focus will be on the current evidence based on randomized clinical trials and the current guideline recommendations for the treatment of cardiogenic shock. © Georg Thieme Verlag KG A A Stuttgart A A New York A A.


De Medeiros P.,University of Cardiff | Hollands S.,University of Leipzig
Classical and Quantum Gravity | Year: 2013

We show how the rigid conformal supersymmetries associated with a certain class of pseudo-Riemannian spin manifolds define a Lie superalgebra. The even part of this superalgebra contains conformal isometries and constant R-symmetries. The odd part is generated by twistor spinors valued in a particular R-symmetry representation. We prove that any manifold which admits a conformal symmetry superalgebra of this type must generically have dimension less than 7. Moreover, in dimensions 3, 4, 5 and 6, we provide the generic data from which the conformal symmetry superalgebra is prescribed. For conformally flat metrics in these dimensions, and compact R-symmetry, we identify each of the associated conformal symmetry superalgebras with one of the conformal superalgebras classified by Nahm. We also describe several examples for Lorentzian metrics that are not conformally flat. © 2013 IOP Publishing Ltd.


De Medeiros P.,University of Cardiff | Hollands S.,University of Leipzig
Classical and Quantum Gravity | Year: 2013

By conformally coupling vector and hyper multiplets in Minkowski space, we obtain a class of field theories with extended rigid conformal supersymmetry on any Lorentzian 4-manifold admitting twistor spinors. We construct the conformal symmetry superalgebras which describe classical symmetries of these theories and derive an appropriate BRST operator in curved spacetime. In the process, we elucidate the general framework of cohomological algebra which underpins the construction. We then consider the corresponding perturbative quantum field theories. In particular, we examine the conditions necessary for conformal supersymmetries to be preserved at the quantum level, i.e. when the BRST operator commutes with the perturbatively defined S-matrix, which ensures superconformal invariance of amplitudes. To this end, we prescribe a renormalization scheme for time-ordered products that enter the perturbative S-matrix and show that such products obey certain Ward identities in curved spacetime. These identities allow us to recast the problem in terms of the cohomology of the BRST operator. Through a careful analysis of this cohomology, and of the renormalization group in curved spacetime, we establish precise criteria which ensure that all conformal supersymmetries are preserved at the quantum level. As a by-product, we provide a rigorous proof that the beta-function for such theories is one-loop exact. We also briefly discuss the construction of chiral rings and the role of non-perturbative effects in curved spacetime. © 2013 IOP Publishing Ltd.


Ziemer M.,University of Leipzig
JDDG - Journal of the German Society of Dermatology | Year: 2013

Graft-versus-host disease is a complex multiorgan disease which mainly occurs in patients after allogeneic hematopoietic stem cell transplantation. The skin is the most frequently affected organ. Care and therapy of patients requires an interdisciplinary approach with dermatology in a key position. Due to the increasing use of peripheral blood stem cells, the increasing age of transplanted patients, the increasing use of unrelated donors, and the broadening of the indications for hematopoietic stem cell transplantation, the incidence of GVHD has been rising in the last decade. Based on extensive clinical and investigational data, the following article tries to give a practical overview for the specialistís daily routine. © Blackwell Verlag GmbH, Berlin.


Rillich J.,Free University of Berlin | Stevenson P.A.,University of Leipzig
Hormones and Behavior | Year: 2014

Social defeat, i.e. losing an agonistic dispute with a conspecific, is followed by a period of suppressed aggressiveness in many animal species, and is generally regarded as a major stressor, which may play a role in psychiatric disorders such as depression and post-traumatic stress disorder. Despite numerous animal models, the mechanisms underlying loser depression and subsequent recovery are largely unknown. This study on crickets is the first to show that a neuromodulator, dopamine (DA), is necessary for recovery of aggression after social defeat. Crickets avoid any conspecific male just after defeat, but regain their aggressiveness over 3. h. This recovery was prohibited after depleting nervous stores of DA and octopamine (OA, the invertebrate analogue of noradrenaline) with α-methyl-tyrosine (AMT). Loser recovery was also prohibited by the insect DA-receptor (DAR) antagonist fluphenazine, but not the OA-receptor (OAR) blocker epinastine, or yohimbine, which blocks receptors for OA's precursor tyramine. Conversely, aggression was restored prematurely in both untreated and amine depleted losers given either chlordimeform (CDM), a tissue permeable OAR-agonist, or the DA-metabolite homovanillyl alcohol (HVA), a component of the honeybee queen mandibular pheromone. As in honeybees, HVA acts in crickets as a DAR-agonist since its aggression promoting effect on losers was selectively blocked by the DAR-antagonist, but not by the OAR-antagonist. Conversely, CDM's aggression promoting effect was selectively blocked by the OAR-antagonist, but not the DAR-antagonist. Hence, only DA is necessary for recovery of aggressiveness after social defeat, although OA can promote loser aggression independently to enable experience dependent adaptive responses. © 2014 Elsevier Inc.


Vogel A.,University of Leipzig | Feller S.E.,Wabash College
Journal of Membrane Biology | Year: 2012

The preferred conformations of the glycerol region of a phospholipid have been explored using replica exchange molecular dynamics (MD) simulations and compared with the results of standard MD approaches and with experiment. We found that due to isomerization rates in key torsions that are slow on the timescale of atomistic MD simulations, standard MD is not able to produce accurate equilibrium conformer distributions from reasonable trajectory lengths (e.g., on the 100 ns) timescale. Replica exchange MD, however, results in quite efficient sampling due to the rapid increase in isomerization rate with temperature. The equilibrium distributions obtained from replica exchange MD have been compared with the results of experimental nuclear magnetic resonance observations. This comparison suggests that the sampling approach demonstrated here is a valuable tool that can be used in evaluating force fields for molecular simulation of lipids. © 2011 Springer Science+Business Media, LLC.


Paasch U.,University of Leipzig
Aktuelle Dermatologie | Year: 2013

Recent insights to the potential of fractional skin treatments have established standard laser procedures to treat aged and sun-damaged skin and scars. On top of this the concept has been extended to fibrosing conditions, to remove foreign bodies and to treat inflammatory skin diseases. The biggest potential however is foreseen with the option of a contact-free temporary opening of the epidermal barrier (TOR, German: gate) to promote new and intensified treatment regimens. To date those concepts are predominantly experimental although first clinical studies show a better response rate if actinic keratoses are treated by fractional laser intensified PDT in comparison to the conventional PDT. Possible risks may arise from the fact that fractional laser home-devices are available. Used in conjunction with topicals of all origin, toxic and allergic reactions may occur. Principles of current fractional laser interventions are presented as facts while visions are given as fictive future indications. © Georg Thieme Verlag KG Stuttgart ·. New York.


Paasch U.,University of Leipzig | Haedersdal M.,Copenhagen University
Expert Review of Medical Devices | Year: 2011

Ablative fractional resurfacing (AFR) creates microscopic vertical ablated channels that are surrounded by a thin layer of coagulated tissue, constituting the microscopic treatment zones (MTZs). AFR induces epidermal and dermal remodeling, which raises new possibilities for the treatment of a variety of skin conditions, primarily chronically photodamaged skin, but also acne and burn scars. In addition, it is anticipated that AFR can be utilized in the laser-assisted delivery of topical drugs. Clinical efficacy coupled with minimal downtime has driven the development of various fractional ablative laser systems. Fractionated CO2 (10,600-nm), erbium yttrium aluminum garnet, 2940-nm and yttrium scandium gallium garnet, 2790-nm lasers are available. In this article, we present an overview of AFR technology, devices and histopathology, and we summarize the current clinical possibilities with AFR incorporating our personal experience. AFR is still in the exploratory era, and systematic investigations of clinical outcomes related to various system settings are needed.


Knofler G.U.,University of Leipzig
Quintessence international (Berlin, Germany : 1985) | Year: 2011

To investigate the impact on microbiologic variables of full-mouth scaling (FMS) and conventional scaling and root planing (cSRP) after 12 months. In a prospective randomized controlled clinical study, 37 volunteers with moderate chronic periodontitis were treated by FMS or by cSRP in two sessions at 4-week intervals. Clinical attachment level, probing depth, and bleeding on probing were recorded at baseline as well as at 6 and 12 months. Four subgingival plaque samples were taken from the deepest sites in premolars and molars at baseline and after 12 months. Pooled sample analysis was performed using real-time polymerase chain reaction for the identification of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. At baseline, the bacterial load of A actinomycetemcomitans was significantly higher in the cSRP group compared to the FMS group (P = .042). In the cSRP group, this load decreased significantly (P = .011), leading to similar quantities of A actinomycetemcomitans in both groups. Further, significant reductions in frequency were found in the FMS group for T forsythia and P gingivalis and in the cSRP group for A actinomycetemcomitans and T denticola. The data suggest that both therapy modalities lead to similar effects on target periodontal pathogen species. FMS compared to cSRP was not favorable in reduction of periodontopathogens.


Masuda N.,University of Tokyo | Klemm K.,University of Leipzig | Eguiluz V.M.,Institute Fisica Interdisciplinar y Sistemas Complejos IFISC CSIC UIB
Physical Review Letters | Year: 2013

Interactions among units in complex systems occur in a specific sequential order, thus affecting the flow of information, the propagation of diseases, and general dynamical processes. We investigate the Laplacian spectrum of temporal networks and compare it with that of the corresponding aggregate network. First, we show that the spectrum of the ensemble average of a temporal network has identical eigenmodes but smaller eigenvalues than the aggregate networks. In large networks without edge condensation, the expected temporal dynamics is a time-rescaled version of the aggregate dynamics. Even for single sequential realizations, diffusive dynamics is slower in temporal networks. These discrepancies are due to the noncommutability of interactions. We illustrate our analytical findings using a simple temporal motif, larger network models, and real temporal networks. Published by American Physical Society.


Castaneda J.M.M.,University of Leipzig | Guilarte J.M.,University of Salamanca | Mosquera A.M.,University of Salamanca | Mosquera A.M.,University of Caldas
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

In this paper the quantum vacuum energies induced by massive fluctuations of one real scalar field on a configuration of two partially transparent plates are analyzed. The physical properties of the infinitely thin plates are characterized by two Dirac-δ potentials. We find that an attractive or repulsive Casimir force arises between the plates when the weights of the δ's have equal or different sign. If some of the plates absorb fluctuations below some threshold of energy (the corresponding weight is negative), there is the need to set a minimum mass to the scalar field fluctuations to preserve unitarity in the corresponding quantum field theory. Two repulsive δ interactions are compatible with massless fluctuations. The effect of Dirichlet boundary conditions at the endpoints of the interval (-a,a) on a massless scalar quantum field theory defined on this interval is tantamount to letting the weights of the repulsive δ interactions go to +∞. © 2013 American Physical Society.


Mohr F.W.,University of Leipzig | Morice M.-C.,Hopital Prive Jacques Cartier | Kappetein A.P.,Erasmus University Rotterdam | Feldman T.E.,Evanston Hospital | And 9 more authors.
The Lancet | Year: 2013

Background We report the 5-year results of the SYNTAX trial, which compared coronary artery bypass graft surgery (CABG) with percutaneous coronary intervention (PCI) for the treatment of patients with left main coronary disease or three-vessel disease, to confirm findings at 1 and 3 years. Methods The randomised, clinical SYNTAX trial with nested registries took place in 85 centres in the USA and Europe. A cardiac surgeon and interventional cardiologist at each centre assessed consecutive patients with de-novo three-vessel disease or left main coronary disease to determine suitability for study treatments. Eligible patients suitable for either treatment were randomly assigned (1:1) by an interactive voice response system to either PCI with a first-generation paclitaxel-eluting stent or to CABG. Patients suitable for only one treatment option were entered into either the PCI-only or CABG-only registries. We analysed a composite rate of major adverse cardiac and cerebrovascular events (MACCE) at 5-year follow-up by Kaplan-Meier analysis on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT00114972. Findings 1800 patients were randomly assigned to CABG (n=897) or PCI (n=903). More patients who were assigned to CABG withdrew consent than did those assigned to PCI (50 vs 11). After 5 years' follow-up, Kaplan-Meier estimates of MACCE were 26•9% in the CABG group and 37•3% in the PCI group (p<0•0001). Estimates of myocardial infarction (3•8% in the CABG group vs 9•7% in the PCI group; p<0•0001) and repeat revascularisation (13•7% vs 25•9%; p<0•0001) were significantly increased with PCI versus CABG. All-cause death (11•4% in the CABG group vs 13•9% in the PCI group; p=0•10) and stroke (3•7% vs 2•4%; p=0•09) were not significantly different between groups. 28•6% of patients in the CABG group with low SYNTAX scores had MACCE versus 32•1% of patients in the PCI group (p=0•43) and 31•0% in the CABG group with left main coronary disease had MACCE versus 36•9% in the PCI group (p=0•12); however, in patients with intermediate or high SYNTAX scores, MACCE was significantly increased with PCI (intermediate score, 25•8% of the CABG group vs 36•0% of the PCI group; p=0•008; high score, 26•8% vs 44•0%; p<0•0001). Interpretation CABG should remain the standard of care for patients with complex lesions (high or intermediate SYNTAX scores). For patients with less complex disease (low SYNTAX scores) or left main coronary disease (low or intermediate SYNTAX scores), PCI is an acceptable alternative. All patients with complex multivessel coronary artery disease should be reviewed and discussed by both a cardiac surgeon and interventional cardiologist to reach consensus on optimum treatment. Funding Boston Scientific.


Auer B.R.,University of Leipzig
Energy Economics | Year: 2014

In this article, we test for the existence of daily seasonality in returns and volatilities of crude oil. Using a dummy-augmented GARCH specification for the period from May 1987 to October 2013, our key findings are as follows: (i) Volatilities on Mondays are significantly higher than on all other weekdays, providing the important insight that seasonal effects should be considered when forecasting crude oil volatility. (ii) Returns on the other hand tend to be lower on Mondays than on other weekdays, suggesting profitable investment strategies based on this seasonal pattern. In fact, the analysis of a simple long-short trading rule based on the Monday effect provides some evidence that it can outperform a passive buy-and-hold approach. However, it cannot do so to an extent that is statistically significant. (iii) Our seasonality results are fairly robust to the choice of other frequently used GARCH model variants, like GARCH-M, TGARCH and CGARCH. © 2014 Elsevier B.V.


Asorey M.,University of Zaragoza | Munoz-Castaneda J.M.,University of Leipzig
Nuclear Physics B | Year: 2013

The infrared behaviour of quantum field theories confined in bounded domains is strongly dependent on the shape and structure of space boundaries. The most significant physical effect arises in the behaviour of the vacuum energy. The Casimir energy can be attractive or repulsive depending on the nature of the boundary. We calculate the vacuum energy for a massless scalar field confined between two homogeneous parallel plates with the most general type of boundary conditions depending on four parameters. The analysis provides a powerful method to identify which boundary conditions generate attractive or repulsive Casimir forces between the plates. In the interface between both regimes we find a very interesting family of boundary conditions which do not induce any type of Casimir force. We also show that the attractive regime holds far beyond identical boundary conditions for the two plates required by the Kenneth-Klich theorem and that the strongest attractive Casimir force appears for periodic boundary conditions whereas the strongest repulsive Casimir force corresponds to anti-periodic boundary conditions. Most of the analysed boundary conditions are new and some of them can be physically implemented with metamaterials. © 2013 Elsevier B.V.


Nauheimer L.,Ludwig Maximilians University of Munich | Nauheimer L.,University of Leipzig | Metzler D.,Ludwig Maximilians University of Munich | Renner S.S.,Ludwig Maximilians University of Munich
New Phytologist | Year: 2012

The family Araceae (3790 species, 117 genera) has one of the oldest fossil records among angiosperms. Ecologically, members of this family range from free-floating aquatics (Pistia and Lemna) to tropical epiphytes. Here, we infer some of the macroevolutionary processes that have led to the worldwide range of this family and test how the inclusion of fossil (formerly occupied) geographical ranges affects biogeographical reconstructions. Using a complete genus-level phylogeny from plastid sequences and outgroups representing the 13 other Alismatales families, we estimate divergence times by applying different clock models and reconstruct range shifts under different models of past continental connectivity, with or without the incorporation of fossil locations. Araceae began to diversify in the Early Cretaceous (when the breakup of Pangea was in its final stages), and all eight subfamilies existed before the K/T boundary. Early lineages persist in Laurasia, with several relatively recent entries into Africa, South America, South-East Asia and Australia. Water-associated habitats appear to be ancestral in the family, and DNA substitution rates are especially high in free-floating Araceae. Past distributions inferred when fossils are included differ in nontrivial ways from those without fossils. Our complete genus-level time-scale for the Araceae may prove to be useful for ecological and physiological studies. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.


The paediatric Hodgkin lymphoma treatment optimisation concepts aim at reduction of treatment intensity with preservation of the high cure rates. A negative interim FDG-PET result after 2 cycles of chemotherapy is associated with a good prognosis. In the current EuroNet-PHL-C1 study radiotherapy is being omitted, if interim PET becomes negative. In addition to the early interim PET after 2 cycles of chemotherapy, all patients undergo an initial PET investigation which is part of the staging processs and plays an essential role for the interpretation of the interim PET. Skeletal involvement can be detected by a typical FDG-PET uptake pattern with high sensitivity and specifi ty. Therefore, in the forthcoming EuroNet-PHL-C2 study bone marrow biopsy and bone scintigraphy will no longer be part of the staging algorithm. © Georg Thieme Verlag KG Stuttgart • New York.


Baumann R.,University of Leipzig
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2011

Splitting results in non-mononotonic formalisms have a long tradition. On the one hand, these results can be used to improve existing computational procedures, and on the other hand they yield deeper theoretical insights into how a non-monotonic approach works. In the 90's Lifschitz and Turner [1,2] proved splitting results for logic programs and default theory. In this paper we establish similar results for Dung style argumentation frameworks (AFs) under the most important semantics, namely stable, preferred, complete and grounded semantics. Furthermore we show how to use these results in dynamical argumentation. © 2011 Springer-Verlag Berlin Heidelberg.


Kotschote M.,University of Leipzig
Journal of Mathematical Fluid Mechanics | Year: 2010

The aim of this work is to prove an existence and uniqueness result for a non-isothermal model of capillary compressible fluids derived by J. E. Dunn and J. Serrin (1985). The proof is essentially based on the maximal regularity result of the associated linear problem, where we can fall back upon useful results proved before. Using the maximal regularity the nonlinear problem can be approached by the contraction mapping principle. © 2009 Birkhäuser Verlag, Basel.


Bendixen A.,University of Leipzig | Bendixen A.,Hungarian Academy of Sciences | Andersen S.K.,University of California at San Diego
Clinical Neurophysiology | Year: 2013

Objectives: Combining behavioral and neurophysiological measurements inevitably implies mutual constraints, such as when the neurophysiological measurement requires fast-paced stimulus presentation and hence the attribution of a behavioral response to a particular preceding stimulus becomes ambiguous. We develop and test a method for validly assessing behavioral detection performance in spite of this ambiguity. Methods: We examine four approaches taken in the literature to treat such situations. We analytically derive a new variant of computing the classical parameters of signal detection theory, hit and false alarm rates, adapted to fast-paced paradigms. Results: Each of the previous approaches shows specific shortcomings (susceptibility towards response window choice, biased estimates of behavioral detection performance). Superior performance of our new approach is demonstrated for both simulated and empirical behavioral data. Further evidence is provided by reliable correspondence between behavioral performance and the N2b component as an electrophysiological indicator of target detection. Conclusions: The appropriateness of our approach is substantiated by both theoretical and empirical arguments. Significance: We demonstrate an easy-to-implement solution for measuring target detection performance independent of the rate of event presentation. Thus overcoming the measurement bias of previous approaches, our method will help to clarify the behavioral relevance of different measures of cortical activation. © 2012 International Federation of Clinical Neurophysiology.


Pirozhenko I.G.,Joint Institute for Nuclear Research | Bordag M.,University of Leipzig
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

The electromagnetic vacuum energy is considered in the presence of a perfectly conducting plane and a ball with dielectric permittivity ε and magnetic permeability μ, μ≠1. The attention is focused on the Casimir repulsion in this system caused by the magnetic permeability of the sphere. In the case of a perfectly permeable sphere, μ=∞, the vacuum energy is estimated numerically. The short- and long-distance asymptotes corresponding to the repulsive force and respective low-temperature corrections and high-temperature limits are found for a wide range of μ. The constraints on the Casimir repulsion in this system are discussed. © 2013 American Physical Society.


Renner R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Simon J.C.,University of Leipzig
Journal of Dermatological Science | Year: 2012

Background: Chronic wounds are both time consuming as well as costly. A new therapeutic option for those wounds might be amelogenin, which supplies a temporary matrix to the fibroblasts and keratinocytes. Objective: To prove the hypotheses for a divergent therapeutic outcome, we treated granulated vs. sclerotic chronic venous leg ulcers with amelogenin (Xelma ®) 1×/week for 5-8weeks. Methods: The analysis of the treatment was performed by applying a recently published mathematical model. This model can predict and evaluate different wound treatment methods by treating only few patients which is even more practicable for diseases with different influencing factors within patients groups because it is easier to collect only a small homogenous number of patients than multiple. Results: We treated 12 granulated vs. 16 sclerotic ulcerations. 5 (42%) of the granulated ulcerations with a mean initial wound area of 18.3cm 2 showed optimal wound healing (>90% epithelization). The average area of new epithelia was 11.9cm 2.Nine (56%) of the sclerotic ulcerations showed optimal wound healing with an initial wound area of 7.5cm 2 and a total average area of 4.1cm 2 with new epithelia. For comparison of those groups, we extrapolate to a hypothetic mean sclerotic wound area of 18.3cm 2 analogue to the granulated ulcerations. This calculates to a mean neoepithel of only 6cm 2 for sclerotic ulcerations. Further on, we calculated about 2% of the wound area that proliferated in contrast to about 3% in granulated wounds. Conclusions: Although sclerotic ulcerations show higher growth rates, Xelma ® seems to be more effective in granulated ulcerations. For larger sclerotic ulcerations the mean maximal covered wound area with neoepithelia is reduced to about 33% in contrast to 65% in granulated ulcerations. © 2012 Japanese Society for Investigative Dermatology.


Heiker J.T.,University of Leipzig
Journal of Peptide Science | Year: 2014

While genome-wide association studies as well as candidate gene studies have revealed a great deal of insight into the contribution of genetics to obesity development and susceptibility, advances in adipose tissue research have substantially changed the understanding of adipose tissue function. Its perception has changed from passive lipid storage tissue to active endocrine organ regulating and modulating whole-body energy homeostasis and metabolism and inflammatory and immune responses by secreting a multitude of bioactive molecules, termed adipokines. The expression of human vaspin (serpinA12) is positively correlated to body mass index and insulin sensitivity and increases glucose tolerance in vivo, suggesting a compensatory role in response to diminished insulin signaling in obesity. Recently, considerable insight has been gained into vaspin structure, function, and specific target tissue-dependent effects, and several lines of evidence suggest vaspin as a promising candidate for drug development for the treatment of obesity-related insulin resistance and inflammation. These will be summarized in this review with a focus on molecular mechanisms and pathways. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.


Baumann R.,University of Leipzig
Frontiers in Artificial Intelligence and Applications | Year: 2014

Notions of equivalence which guarantee intersubstitutability w.r.t. further modifications have received considerable interest in nonmonotonic reasoning. This paper is within the context of abstract argumentation and we focus on the most general form of a dynamic scenarios, so-called updates as well as certain sub-classes, namely local, normal and arbitrary deletions. We provide characterization theorems for the corresponding equivalence notions and draw the relations to the recently proposed kinds of expansion equivalence [15, 3]. Many of the results rely on abstract concepts like context-free kernels or semantics satisfying isolate-inclusion. Therefore, the results may apply to future semantics as well as further equivalence notions. © 2014 The Authors and IOS Press.


Ngomo A.-C.N.,University of Leipzig
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2014

Links between knowledge bases build the backbone of the Linked Data Web. In previous works, the combination of the results of time-efficient algorithms through set-theoretical operators has been shown to be very timeefficient for Link Discovery. However, the further optimization of such link specifications has not been paid much attention to. We address the issue of further optimizing the runtime of link specifications by presenting HELIOS, a runtime optimizer for Link Discovery. HELIOS comprises both a rewriter and an execution planner for link specifications. The rewriter is a sequence of fixed-point iterators for algebraic rules. The planner relies on time-efficient evaluation functions to generate execution plans for link specifications. We evaluate HELIOS on 17 specifications created by human experts and 2180 specifications generated automatically. Our evaluation shows that HELIOS is up to 300 times faster than a canonical planner. Moreover, HELIOS’ improvements are statistically significant. © Springer International Publishing Switzerland 2014.


Ziemer M.,University of Leipzig | Kardaun S.H.,University of Groningen | Liss Y.,Albert Ludwigs University of Freiburg | Mockenhaupt M.,Albert Ludwigs University of Freiburg
British Journal of Dermatology | Year: 2012

Background Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions with high morbidity and mortality. Some expressions of lupus erythematosus (LE) may cause enormous difficulties in differentiating them from SJS and TEN by showing large areas of sheet-like epidermal necrosis. Objective To evaluate clinically and histopathologically probable or definite cases of SJS/TEN with a history of systemic or other LE [(S)LE]. Methods This was a retrospective analysis of validated cases of SJS/TEN with a history of (S)LE, based on a large population-based national registry. Results Among 1366 patients with SJS/TEN, 17 with a sufficiently documented history of (S)LE and representative histological material could be identified, suggesting a considerable over-representation of LE in patients with SJS/TEN. Eight of these showed clinically and/or histopathologically some LE-characteristic features interfering with the diagnosis of SJS/TEN. Differentiation could be elaborated on clinical and histopathological grounds: four patients were classified as SJS/TEN with a preceding (S)LE exacerbation and/or LE-typical histopathological features, and four as 'TEN-like' (S)LE. Conclusion Most patients with SJS/TEN and a history of (S)LE demonstrate clinical and histopathological properties allowing clear differentiation. However, occasionally acute cutaneous manifestations of (S)LE and SJS/TEN can be phenotypically similar, caused by extensive epidermal necrosis. Although no feature by itself is conclusive, a combination of recent (S)LE exacerbation, evident photodistribution, annular lesions and absent or only mild focal erosive mucosal involvement may favour LE over SJS/TEN clinically. Histopathologically, in particular, junctional vacuolar alteration, and the presence of solitary necrotic keratinocytes at lower epidermal levels, combined with moderate to dense periadnexal and perivascular lymphocytic infiltrates with a variable presence of melanophages, and mucin point to a LE-related origin. © 2011 The Authors. BJD © 2011 British Association of Dermatologists.


Hlawitschka M.,University of Leipzig
IEEE transactions on ultrasonics, ferroelectrics, and frequency control | Year: 2011

Real-time beam predictions are highly desirable for the patient-specific computations required in ultrasound therapy guidance and treatment planning. To address the longstanding issue of the computational burden associated with calculating the acoustic field in large volumes, we use graphics processing unit (GPU) computing to accelerate the computation of monochromatic pressure fields for therapeutic ultrasound arrays. In our strategy, we start with acceleration of field computations for single rectangular pistons, and then we explore fast calculations for arrays of rectangular pistons. For single-piston calculations, we employ the fast near-field method (FNM) to accurately and efficiently estimate the complex near-field wave patterns for rectangular pistons in homogeneous media. The FNM is compared with the Rayleigh-Sommerfeld method (RSM) for the number of abscissas required in the respective numerical integrations to achieve 1%, 0.1%, and 0.01% accuracy in the field calculations. Next, algorithms are described for accelerated computation of beam patterns for two different ultrasound transducer arrays: regular 1-D linear arrays and regular 2-D linear arrays. For the array types considered, the algorithm is split into two parts: 1) the computation of the field from one piston, and 2) the computation of a piston-array beam pattern based on a pre-computed field from one piston. It is shown that the process of calculating an array beam pattern is equivalent to the convolution of the single-piston field with the complex weights associated with an array of pistons. Our results show that the algorithms for computing monochromatic fields from linear and regularly spaced arrays can benefit greatly from GPU computing hardware, exceeding the performance of an expensive CPU by more than 100 times using an inexpensive GPU board. For a single rectangular piston, the FNM method facilitates volumetric computations with 0.01% accuracy at rates better than 30 ns per field point. Furthermore, we demonstrate array calculation speeds of up to 11.5 X 10(9) field-points per piston per second (0.087 ns per field point per piston) for a 512-piston linear array. Beam volumes containing 256(3) field points are calculated within 1 s for 1-D and 2-D arrays containing 512 and 20(2) pistons, respectively, thus facilitating future real-time thermal dose predictions.


Harrison C.,Guys and St Thomas NHS Foundation Trust | Kiladjian J.-J.,University Paris Diderot | Al-Ali H.K.,University of Leipzig | Gisslinger H.,Medical University of Vienna | And 10 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Treatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis. METHODS: We assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy. The primary end point and key secondary end point of the study were the percentage of patients with at least a 35% reduction in spleen volume at week 48 and at week 24, respectively, as assessed with the use of magnetic resonance imaging or computed tomography. RESULTS: A total of 28% of the patients in the ruxolitinib group had at least a 35% reduction in spleen volume at week 48, as compared with 0% in the group receiving the best available therapy (P<0.001); the corresponding percentages at week 24 were 32% and 0% (P<0.001). At 48 weeks, the mean palpable spleen length had decreased by 56% with ruxolitinib but had increased by 4% with the best available therapy. The median duration of response with ruxolitinib was not reached, with 80% of patients still having a response at a median follow-up of 12 months. Patients in the ruxolitinib group had an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. The most common hematologic abnormalities of grade 3 or higher in either group were thrombocytopenia and anemia, which were managed with a dose reduction, interruption of treatment, or transfusion. One patient in each group discontinued treatment owing to thrombocytopenia, and none discontinued owing to anemia. Nonhematologic adverse events were rare and mostly grade 1 or 2. Two cases of acute myeloid leukemia were reported with the best available therapy. CONCLUSIONS: Continuous ruxolitinib therapy, as compared with the best available therapy, was associated with marked and durable reductions in splenomegaly and disease-related symptoms, improvements in role functioning and quality of life, and modest toxic effects. An influence on overall survival has not yet been shown. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00934544.). Copyright © 2012 Massachusetts Medical Society.


Kortmann R.-D.,University of Leipzig
Expert Review of Anticancer Therapy | Year: 2014

Radiation therapy is the backbone in the management of intracranial germinoma. In localized disease chemotherapy followed by whole brain irradiation is the present standard providing cure rates in excess of 90%. Craniospinal irradiation alone in metastatic disease provides equally excellent outcome. Chemotherapy is able to convert macroscopic to microscopic disease permitting a dose reduction to the tumor site and possibly the ventricular system and is investigated in prospective trials. Chemotherapy alone cannot replace radiotherapy as sole treatment. Whole-ventricular radiotherapy followed by a boost to tumor site without chemotherapy might be feasible. New treatment technologies such as intensity-modulated radiotherapy or proton therapy permit a dose reduction to non-target brain. Data on functional outcome are conflicting and based on small heterogeneous series only mandating prospective investigations. © 2014 Informa UK, Ltd.


Fletcher W.J.,Goethe University Frankfurt | Fletcher W.J.,University of Manchester | Zielhofer C.,University of Leipzig
Catena | Year: 2013

In this paper we explore the evidence for Holocene Rapid Climate Changes (RCCs) in Western Mediterranean records, examining similarities and differences in the timing and nature of impacts on different components of the natural environment (vegetation, fluvial and coastal sedimentation, fire activity, soil formation). Marine, lacustrine, and fluvial archives of the Western Mediterranean (Iberian Peninsula and Northwest Africa) provide evidence for both pervasive millennial-scale climatic variability and abrupt (decadal- to centennial-scale) transitions. We focus in particular on three RCCs characterised by high-latitude cooling, glacier advances and North-Atlantic ice-rafting events: the mid-Holocene RCC interval 6-5. cal. ka BP, the late-Holocene RCC interval 3.5-2.5. cal. ka BP, and the historical RCC interval known as the Little Ice Age (LIA, 1300-1950. AD). Evidence from multiple records indicates wide-ranging impacts of RCCs in the Western Mediterranean region. The three RCC intervals were characterised, however, by contrasting hydrological situations in the Western Mediterranean, with prevailing dry conditions including marked aridification events during the RCC intervals 6-5 and 3.5-2.5. cal. ka BP, and prevailing or recurrent wet conditions during the LIA. We examine issues of proxy sensitivity in palaeoecological and geomorphological records and evaluate examples of contrasting geomorphological responses to regional climatic triggers between humid and semi-arid sectors of the Western Mediterranean. Finally, we consider the long-term sensitivity of the region to rapid climate change, the role of threshold changes, and the extent to which this region represents a "fragile" landscape. © 2011 Elsevier B.V.


Berg T.,University of Leipzig
Current Topics in Microbiology and Immunology | Year: 2010

The transcription factor c-Myc is overexpressed in many tumors in human beings and has been identified as a highly promising target for cancer therapy. Most biological functions of c-Myc require heterodimerization with its activation partner Max. Inhibition of the protein-protein interactions between c-Myc and Max by small molecules has been shown to be a feasible and powerful approach toward the inhibition of c-Myc functions. More recently, stabilization of Max homodimers to reduce the amount of Max available for activating c-Myc has also been demonstrated to counteract Myc activity. This review summarizes our current knowledge on small organic molecules that inhibit c-Myc by modulating protein-protein interactions relevant for the biological function of this important oncoprotein. © Springer-Verlag Berlin Heidelberg 2011.


Mierke C.T.,University of Leipzig | Mierke C.T.,Friedrich - Alexander - University, Erlangen - Nuremberg
New Journal of Physics | Year: 2013

The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock-down cells and αvβ3low cells was not altered. In summary, these results suggest that the αvβ3 integrin enhances cancer cell invasion through increased cellular stiffness and enhanced cytoskeletal remodeling dynamics, which enables the cells to generate and transmit contractile forces to overcome the steric hindrance of 3D ECMs. © IOP Publishing and Deutsche Physikalische Gesellschaft.


Allgaier M.,Institute Of Biomedicina Ibub | Allgaier C.,University of Leipzig | Allgaier C.,ACA Pharma Concept GmbH
Frontiers in Bioscience - Landmark | Year: 2014

Alzheimer's disease (AD) is characterized by progressive decrease in cognitive function and loss of short-term memory known to be associated with a dysfunction of the cholinergic system. The pathological hallmarks of AD are beta-amyloid (Abeta) plaques and neurofibrillary tangles (NFTs) consisting of hyperphosphorylated tau. Hypercholesterolemia and disturbances in glucose metabolism are another risk factors. During the last two decades therapeutic strategies were mainly targeting the Abeta hypothesis. As this approach virtually failed to show a significant clinical benefit research on potential therapeutics has been shifted to tau pathology. However, also this approach has as yet not yielded in new therapeutics. Hence, rebalancing the cholinergic input to improve the cognitive symptoms of AD by inhibition of acetylcholine esterase (AChE) is still the only mechanistic target in addition to N-methyl-D-aspartate (NMDA) receptor blockade by memantine that can be addressed by currently approved medications. Despite the fact that the available AChE inhibitors are directed at an identical target they exhibit some pharmacodynamic and pharmacokinetic features that should be considered when used clinically.


Mood may be associated with several aspects of psychopathology. Though mood is more context dependent than other psychological variables it is useful to calculate norms. Based on a representative sample of the German general population (N=2 443), mood was assessed with the Multidimensional Mood Questionnaire MDBF (short form A). The correlations among the 3 bipolar scales (good - bad mood, alertness - tiredness and calmness - restlessness) ranged between 0.70 and 0.75. Good mood and alertness decline with increasing age. Males (compared to females) show higher mean values in alertness and calmness. The mean scores presented in this article can be used as comparison values for clinical samples. © Georg Thieme Verlag KG Stuttgart · New York.


Przybilla J.,The Interdisciplinary Center | Rohlf T.,The Interdisciplinary Center | Rohlf T.,Max Planck Institute for Mathematics in the Sciences | Loeffler M.,The Interdisciplinary Center | And 2 more authors.
Aging Cell | Year: 2014

Summary: During aging, a decline in stem cell function is observed in many tissues. This decline is accompanied by complex changes of the chromatin structure among them changes in histone modifications and DNA methylation which both affect transcription of a tissue-specific subset of genes. A mechanistic understanding of these age-associated processes, their interrelations and environmental dependence is currently lacking. Here, we discuss related questions on the molecular, cellular, and population level. We combine an individual cell-based model of stem cell populations with a model of epigenetic regulation of transcription. The novel model enables to simulate age-related changes of trimethylation of lysine 4 at histone H3 and of DNA methylation. These changes entail expression changes of genes that induce age-related phenotypes (ARPs) of cells. We compare age-related changes of regulatory states in quiescent stem cells occupying a niche with those observed in proliferating cells. Moreover, we analyze the impact of the activity of the involved epigenetic modifiers on these changes. We find that epigenetic aging strongly affects stem cell heterogeneity and that homing at stem cell niches retards epigenetic aging. Our model provides a mechanistic explanation how increased stem cell proliferation can lead to progeroid phenotypes. Adapting our model to properties observed for aged hematopoietic stem cell (HSC) clones, we predict that the hematopoietic ARP activates young HSCs and thereby retards aging of the entire HSC population. In addition, our model suggests that the experimentally observed high interindividual variance in HSC numbers originates in a variance of histone methyltransferase activity. © 2013 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.


Hagendorff A.,University of Leipzig
Herz | Year: 2012

Echocardiography plays an important role in emergency medicine because this non-invasive method is universally available and provides crucial diagnostic findings for acute decision making. The cardiac etiology in the presence of acute chest pain, acute dyspnea, hemodynamic instability or shock, new heart murmurs, chest trauma, peripheral embolism and cardiac arrest can be determined by echocardiography in the emergency scenario. The analysis of left ventricular function documents myocardial ischemia and myocardial infarction. Analysis of right ventricular function documents right heart infarction, pulmonary embolism, tension pneumothorax and sequelae of chest trauma. Echocardiography differentiates between different entities of shock. The analysis of heart valves is a domain of echocardiography. Affections of the pericardium and the hemodynamic sequelae can also be determined. It is obvious that echocardiography with its multiple diagnostic applications can only be well performed, especially in emergency medicine after in-depth education and training in this method. © 2012 Urban & Vogel, Muenchen.


Lordick F.,University of Leipzig | Kang Y.-K.,Asan Medical Center | Chung H.-C.,Yonsei University | Salman P.,Fundacion Arturo Lopez Perez | And 12 more authors.
The Lancet Oncology | Year: 2013

Background: Patients with advanced gastric cancer have a poor prognosis and few efficacious treatment options. We aimed to assess the addition of cetuximab to capecitabine-cisplatin chemotherapy in patients with advanced gastric or gastro-oesophageal junction cancer. Methods: In our open-label, randomised phase 3 trial (EXPAND), we enrolled adults aged 18 years or older with histologically confirmed locally advanced unresectable (M0) or metastatic (M1) adenocarcinoma of the stomach or gastro-oesophageal junction. We enrolled patients at 164 sites (teaching hospitals and clinics) in 25 countries, and randomly assigned eligible participants (1:1) to receive first-line chemotherapy with or without cetuximab. Randomisation was done with a permuted block randomisation procedure (variable block size), stratified by disease stage (M0 vs M1), previous oesophagectomy or gastrectomy (yes vs no), and previous (neo)adjuvant (radio)chemotherapy (yes vs no). Treatment consisted of 3-week cycles of twice-daily capecitabine 1000 mg/m2 (on days 1-14) and intravenous cisplatin 80 mg/m2 (on day 1), with or without weekly cetuximab (400 mg/m2 initial infusion on day 1 followed by 250 mg/m2 per week thereafter). The primary endpoint was progression-free survival (PFS), assessed by a masked independent review committee in the intention-to-treat population. We assessed safety in all patients who received at least one dose of study drug. This study is registered at EudraCT, number 2007-004219-75. Findings: Between June 30, 2008, and Dec 15, 2010, we enrolled 904 patients. Median PFS for 455 patients allocated capecitabine-cisplatin plus cetuximab was 4·4 months (95% CI 4·2-5·5) compared with 5·6 months (5·1-5·7) for 449 patients who were allocated to receive capecitabine-cisplatin alone (hazard ratio 1·09, 95% CI 0·92-1·29; p=0·32). 369 (83%) of 446 patients in the chemotherapy plus cetuximab group and 337 (77%) of 436 patients in the chemotherapy group had grade 3-4 adverse events, including grade 3-4 diarrhoea, hypokalaemia, hypomagnesaemia, rash, and hand-foot syndrome. Grade 3-4 neutropenia was more common in controls than in patients who received cetuximab. Incidence of grade 3-4 skin reactions and acne-like rash was substantially higher in the cetuximab-containing regimen than in the control regimen. 239 (54%) of 446 in the cetuximab group and 194 (44%) of 436 in the control group had any grade of serious adverse event. Interpretation: Addition of cetuximab to capecitabine-cisplatin provided no additional benefit to chemotherapy alone in the first-line treatment of advanced gastric cancer in our trial. Funding: Merck KGaA. © 2013 Elsevier Ltd.


Wittenburg H.,University of Leipzig
Best Practice and Research: Clinical Gastroenterology | Year: 2010

Gallstones are common in Western countries and due to pain and complications pose a substantial burden on health care systems. In general, cholesterol gallstones are distinguished from bilirubin gallstones. Bilirubin gallstones form if the ion product of unconjugated bilirubin and calcium in gallbladder bile exceeds the solubilisation capacities of mixed micelles and vesicles. Cholesterol gallstones develop if the amount of cholesterol in gallbladder bile exceeds the maximum concentration that is soluble at the given concentration of bile salts and phospholipids. In addition, cholesterol gallstone formation requires hypomotility of the gallbladder and a mucin gel as nucleation matrix for monohydrate crystals. The individual risk of gallstone formation is determined by interactions of lithogenic alleles of gallstone susceptibility genes and multiple environmental factors. For asymptomatic gallstones, expectant management is recommended, whereas an episode of gallstone-associated pain substantially increases the risk of complications such as cholecystitis, cholangitis and pancreatitis and therefore necessitates cholecystectomy. © 2010 Elsevier Ltd. All rights reserved.


Background: Binge eating disorder is a prevalent adolescent disorder, associated with increased eating disorder and general psychopathology as well as an increased risk for overweight and obesity. As opposed to binge eating disorder in adults, there is a lack of validated psychological treatments for this condition in adolescents. The goal of this research project is therefore to determine the efficacy of age-adapted cognitive-behavioral therapy in adolescents with binge eating disorder - the gold standard treatment for adults with binge eating disorder.Methods/design: In a single-center efficacy trial, 60 12- to 20-year-old adolescents meeting diagnostic criteria of binge eating disorder (full-syndrome or subthreshold) according to the Diagnostic and Statistical Manual of Mental Disorders 4th or 5th Edition, will be centrally randomized to 4 months of cognitive-behavioral therapy (n = 30) or a waiting-list control condition (n = 30). Using an observer-blind design, patients are assessed at baseline, mid-treatment, post-treatment, and at 6- and 12-month follow-ups after the end of treatment. In 20 individual outpatient sessions, cognitive-behavioral therapy for adolescents focuses on eating behavior, body image, and stress; parents receive psychoeducation on these topics. Primary endpoint is the number of episodes with binge eating over the previous 28 days at post-treatment using a state-of-the art clinical interview. Secondary outcome measures address the specific eating disorder psychopathology, general psychopathology, mental comorbidity, self-esteem, quality of life, and body weight.Discussion: This trial will allow us to determine the short- and long-term efficacy of cognitive-behavioral therapy in adolescent binge eating disorder, to determine cost-effectiveness, and to identify predictors of treatment outcome. Evidence will be gathered regarding whether this treatment will help to prevent excessive weight gain. If efficacy can be demonstrated, the results from this trial will enhance availability of evidence-based treatment of adolescent binge eating disorder.Trial registration: German Clinical Trials Register: DRKS00000542. © 2013 Hilbert; licensee BioMed Central Ltd.


Wolf T.,University of Leipzig | Meyer B.C.,TU Dortmund
Ecological Indicators | Year: 2010

Housing suburbanisation led in the past decades to problems caused by deconcentration of population and intensive area-consumption. Major social, economic and ecological functions for a sustainable spatial decision support in the suburban landscape are described and functionalised by indicators and modelled using GIS with the aim to minimise the problems related to the suburbanisation. The indicators chosen include human-ecological functions, accessibility and infrastructure development and the regulation and regeneration of population and biocoenosis. Out of a balanced list of 11 indicators (one is used twice) the regulation of traffic noise immissions, the landscape accessibility to the nearest freeway and the habitat network integration of sites are modelled, assessed and discussed detailed. The indicator modelling operationalises a wide range of methods including the analysis of travel costs, distance functions, visibility analysis and landscape metrics on the basis of public available data (biotope types, digital elevation model and road data). The methods are applied to a suburban agricultural landscape northeast of Leipzig in Saxony/Germany (66 km2). Three scenarios developed for the aggregation of multiple considerations are demonstrated with maps - based on the status quo of the "(mono)-functional landscape", the "multi functional landscape" and the "sustainable landscape". The scenarios aggregate an increasing number of indicators to form a comprehensive assessment. The result maps clearly show the suitable areas for private housing that fulfil e.g. silence, recreational functions while simultaneously ensuring nature protection. The paper emphasises the integrative prospects of landscape functions for monitoring, indicator assessment and the integration to land use decision-making in the context of spatial planning. © 2009 Elsevier Ltd. All rights reserved.


Zahn S.,University of Leipzig | Stark A.,TU Darmstadt
Physical Chemistry Chemical Physics | Year: 2015

The dissolution of 1-alkyl-3-methylimidazolium chloride ILs with short alkyl chains in trihexyltetradecylphosphonium chloride does not only exhibit a large negative entropy. Also, in the resulting mixtures, the phosphonium cation diffuses faster than the much smaller imidazolium cation. Both unexpected features originate from the formation of a large symmetric ion cluster cage in which the imidazolium cation is caught by three chloride anions and four phosphonium cations. © the Owner Societies 2015.


Bernhard M.,University of Leipzig | Benger J.R.,University of Bristol
Current Opinion in Critical Care | Year: 2015

Purpose of review This article evaluates the latest scientific evidence regarding airway management during in-hospital and out-of-hospital cardiopulmonary resuscitation (CPR). Recent findings In the in-hospital setting, observational research suggested that the quality of CPR using 'no flow ratio' as a surrogate marker was improved when advanced airway techniques were used. A registry study demonstrated that an initial failed intubation attempt was associated with an average delay of 3min in time to return of spontaneous circulation. A prospective observational study showed that the Glide Scope videolaryngoscope was associated with a first-pass success rate of 93%, with no differences between less and more experienced physicians. In the out-of-hospital setting, a registry study suggested that intubation leads to a better outcome compared with supraglottic airway devices. However, no advanced airway devices showed a better outcome than basic airway techniques. An observational study reported that the i-gel supraglottic airway device offers a first-pass insertion success rate of 90%, and was easier to establish than the Portex Soft Seal laryngeal mask airway. Other out-of-hospital observational studies showed that the laryngeal tube offers a lower first-pass insertion success rate than expected, and complications of this device may influence later definitive airway management and the outcome as a whole. Summary Recent studies of airway management during CPR rely mostly on registry and observational designs. Prospective randomized trials are needed to determine the optimal approach to airway management during cardiac arrest, but have not yet been completed. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Mossner J.,University of Leipzig
Digestive Diseases | Year: 2010

This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca2+ signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis. Copyright © 2011 S. Karger AG, Basel.


Winkler I.,Hungarian Academy of Sciences | Winkler I.,University of Szeged | Schroger E.,University of Leipzig
Brain and Language | Year: 2015

Communication by sounds requires that the communication channels (i.e. speech/speakers and other sound sources) had been established. This allows to separate concurrently active sound sources, to track their identity, to assess the type of message arriving from them, and to decide whether and when to react (e.g., reply to the message). We propose that these functions rely on a common generative model of the auditory environment. This model predicts upcoming sounds on the basis of representations describing temporal/sequential regularities. Predictions help to identify the continuation of the previously discovered sound sources to detect the emergence of new sources as well as changes in the behavior of the known ones. It produces auditory event representations which provide a full sensory description of the sounds, including their relation to the auditory context and the current goals of the organism. Event representations can be consciously perceived and serve as objects in various cognitive operations. © 2015 The Authors.


Gratwohl A.,University of Basel | Niederwieser D.,University of Leipzig
Current Problems in Dermatology | Year: 2012

Hematopoietic stem cell transplantation (HSCT) has evolved over the last half century from experimental bone marrow transplantation for patients with incurable leukemia or bone marrow failure to standard of care for a broad range of patients with congenital or acquired disorders of the hematopoietic system or radio-, chemo- or immune-sensitive malignancies. More than 60,000 such transplants are currently carried out annually worldwide with increasing frequency. HSCT has always been closely linked to Dermatology from its very beginning through its main and most devastating complication graft-versus-host disease. Treatment complications of HSCT have provided a great deal of insight into basic mechanisms of immunology, clinical medicine and networking in general. It remains a challenge to turn this knowledge from the two disciplines into benefit for the future patients with disturbed immune function and skin diseases. © 2012 S. Karger AG, Basel.


Preschl B.,University of Zurich | Maercker A.,University of Zurich | Wagner B.,University of Leipzig
BMC Psychiatry | Year: 2011

Background: Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy.Methods: This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment.Results: With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group.Conclusions: Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group.Trial registration: ACTRN12611000563965. © 2011 Preschl et al; licensee BioMed Central Ltd.


Berg T.,University of Leipzig
Current topics in microbiology and immunology | Year: 2011

The transcription factor c-Myc is overexpressed in many tumors in human beings and has been identified as a highly promising target for cancer therapy. Most biological functions of c-Myc require heterodimerization with its activation partner Max. Inhibition of the protein-protein interactions between c-Myc and Max by small molecules has been shown to be a feasible and powerful approach toward the inhibition of c-Myc functions. More recently, stabilization of Max homodimers to reduce the amount of Max available for activating c-Myc has also been demonstrated to counteract Myc activity. This review summarizes our current knowledge on small organic molecules that inhibit c-Myc by modulating protein-protein interactions relevant for the biological function of this important oncoprotein.


Uhlmann A.,University of Leipzig
Entropy | Year: 2010

Convex roof extensions are widely used to create entanglement measures in quantum information theory. The aim of the article is to present some tools which could be helpful for their treatment. Sections 2 and 3 introduce into the subject. It follows descriptions of the Wootters' method, of the "subtraction procedure", and examples on how to use symmetries. © 2010.


Rother T.,German Aerospace Center | Wauer J.,University of Leipzig
Applied Optics | Year: 2010

In this paper we discuss the influence of two different sets of weighting functions on the accuracy behavior of T-matrix calculations for scalar scattering problems. The first set of weighting functions is related to one of Waterman's original approaches. The other set results into a least-squares scheme for the transmission problem. It is shown that both sets of weighting functions produce results with a converse accuracy behavior in the near and far fields. Additional information, such as reciprocity and the fulfillment of the boundary condition, are needed to choose the set of weighting functions that is most appropriate for a certain application. The obtained criteria are applied afterward to an iterative T-matrix approach we developed to analyze scattering on regular particle geometries with an impressed but slight surface irregularity. However, its usefulness is demonstrated in this paper by analyzing the far-field scattering behavior of Chebyshev particles of higher orders. © 2010 Optical Society of America.


Our interdisciplinary team is based in a teaching hospital department for psychosomatics and therapeutic interventions for mothers and children. This tertiary service provides assessment and treatment of infants, children and their families presenting with complex and severe feeding disorders. We specialise in the care of children with a variety of multiple problems e. g. presenting after premature birth, and their associated relationship problems. The complexity of issues requires intervention at multiple levels in order to address the individual and family needs of the child. Each case represents opportunities and challenges. The team also addresses integrated services provision across the spectrum of services involved as well as attempting to integrate therapeutic approaches across professional boundaries. This is illustrated by a case report and complemented by a literature review. © Vandenhoeck & Ruprecht GmbH & Co. KG, Göttingen 2011.


Mierke C.T.,University of Leipzig
Cell Biochemistry and Biophysics | Year: 2011

The malignancy of tumors depends on the biomechanical properties of cancer cells and their microenvironment, which enable cancer cells to migrate through the connective tissue, transmigrate through basement membranes and endothelial monolayers and form metastases in targeted organs. The current focus of cancer research is still based on biological capabilities such as molecular genetics and gene signaling, but these approaches ignore the mechanical nature of the invasion process of cancer cells. This review will focus on how structural, biochemical and mechanical properties of extracellular matrices (ECMs), and adjacent cells regulate the invasiveness of cancer cells. In addition, it presents how cancer cells create their own microenvironment by restructuring of the ECM and by interaction with stromal cells, which then further contribute to the progression of cancer disease. Finally, this review will point out that mechanical properties are a critical determinant for the efficiency of cancer cell invasion and the progression of cancer which might affect the future development of new cancer treatments. © 2011 Springer Science+Business Media, LLC.


Eschbach C.,University of Leipzig
Chemical senses | Year: 2011

How are odor mixtures perceived? We take a behavioral approach toward this question, using associative odor-recognition experiments in Drosophila. We test how strongly flies avoid a binary mixture after punishment training with one of its constituent elements and how much, in turn, flies avoid an odor element if it had been a component of a previously punished binary mixture. A distinguishing feature of our approach is that we first adjust odors for task-relevant behavioral potency, that is, for equal learnability. Doing so, we find that 1) generalization between mixture and elements is symmetrical and partial, 2) elements are equally similar to all mixtures containing it and that 3) mixtures are equally similar to both their constituent elements. As boundary conditions for the applicability of these rules, we note that first, although variations in learnability are small and remain below statistical cut-off, these variations nevertheless correlate with the elements' perceptual "weight" in the mixture; thus, even small differences in learnability between the elements have the potential to feign mixture asymmetries. Second, the more distant the elements of a mixture are to each other in terms of their physicochemical properties, the more distant the flies regard the elements from the mixture. Thus, titrating for task-relevant behavioral potency and taking into account physicochemical relatedness of odors reveals rules of mixture perception that, maybe surprisingly, appear to be fairly simple.


Mierke C.T.,University of Leipzig
Cell Adhesion and Migration | Year: 2015

Cellular motility is essential for many processes such as embryonic development, wound healing processes, tissue assembly and regeneration, immune cell trafficing and diseases such as cancer. The migration efficiency and the migratory potential depend on the type of migration mode. The previously established migration modes such as epithelial (non-migratory) and mesenchymal (migratory) as well as amoeboid (squeezing motility) relay mainly on phenomenological criteria such as cell morphology and molecular biological criteria such as gene expression. However, the physical view on the migration modes is still not well understood. As the process of malignant cancer progression such as metastasis depends on the migration of single cancer cells and their migration mode, this review focuses on the different migration strategies and discusses which mechanical prerequisites are necessary to perform a special migration mode through a 3-dimensional microenvironment. In particular, this review discusses how cells can distinguish and finally switch between the migration modes and what impact do the physical properties of cells and their microenvironment have on the transition between the novel migration modes such as blebbing and protrusive motility. © 2015 Taylor and Francis Group, LLC.


Merkenschlager A.,University of Leipzig
Notfall und Rettungsmedizin | Year: 2011

This paper is dedicated to the pediatric emergency "disturbed consciousness and coma". It describes the prehospital management of disturbed consciousness in the pediatric age group. It is primarily meant as a practical guideline for the initial evaluation and treatment in the out-of-hospital setting. The interface between the emergency physician and the admitting emergency room is important; thus, specific recommendations are given concerning subsequent clinical care. The algorithm presented is designed for the emergency scenario "the unconscious child" or "the child with disturbed consciousness," which corresponds to all situations with a Glasgow Coma Scale score less than 15 points. © 2011 Springer-Verlag.


The Childhood Trauma Questionnaire (CTQ) has become internationally accepted as an assessment of traumatic childhood experiences. The short version assesses aspects of childhood abuse and neglect. In order to check the psychometric properties of the German short form, the CTQ was used within a representative sample of the German population (N=2 500). The five factor structure of the original version showed only a sufficient model fit, because of high intercorrelations and weak internal consistency of the scale "physical neglect". The internal consistency of the other subscales was high with α≥0.80. Construct validity was supported by positive correlations with measures of anxiety/depression and negative correlations with life satisfaction. The German short form of the CTQ is a reliable and valid self rating instrument to assess childhood maltreatment retrospectively. The subscale "physical neglect" should be applied with caution. © Georg Thieme Verlag KG Stuttgart · New York.


Scharf N.T.,New York University | Stark A.,University of Leipzig | Hoffmann M.M.,New York University
Journal of Physical Chemistry B | Year: 2012

The structural and dynamic behavior of the ionic liquid 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([C 6mim][NTf2]) in chloroform has been studied by experimental measurements of 1H and 19F self-diffusion coefficients, viscosity, and excess molar volume in the concentration range of 0.001-1.0 mol·kg-1 and temperatures ranging from 15 to 45 °C. Within measurement uncertainty, the 1H and 19F self-diffusion coefficients are identical at the same experimental conditions of concentration and temperature, indicating that even to the lowest measured concentrations the cation and anion are not completely dissociated. The combined experimental data indicates a progression from ion pairing to aggregate formation as concentration increases where at concentrations near 0.1 mol·kg-1 aggregate formation becomes dominant. Concurrently with the formation of the IL aggregates at higher concentrations, we also observe an apparent breakdown of the validity of the Stokes-Einstein equation, which we explain by translational motion to become dominated by individual ion pairs moving rapidly between IL aggregates. © 2012 American Chemical Society.


Tutic A.,University of Leipzig
International Game Theory Review | Year: 2010

In this note we present an example of a TU game where both the value presented by Aumann and Drèze (1974) and the value introduced by Wiese (2007) do not exhibit a stable coalition structure. © 2010 World Scientific Publishing Company.


Morgner H.,University of Leipzig
Journal of Physical Chemistry C | Year: 2010

The hysteresis observed frequently in the adsorption isotherm of gas in porous material is currently subject to intense research. The nature of the hysteresis itself and in particular recent observations on the uptake dynamics inside the hysteresis loop are described as poorly understood puzzles even in recent literature (Wallacher, D.; Künzer, N.; Kovalev, D.; Knorr, N.; Knorr, K. Phys. Rev. Lett. 2004, 92, 195704-1; Valiullin, R.; Naumov, S.; Galvosas, P.; Kärger, J.; Woo, H.-J.; Porcheron, F.; Monson, P. Nature 2006, 443, 965-968). Detailed experiments combined with theoretical efforts have led to the identification of new problems rather than answers, e.g., the relaxation dynamics in pressure jump experiments is found to be "dramatically" slowed down inside the hysteresis loop (Valiullin et al. 2006). This has motivated the authors to postulate "a fundamental difference in the nature of the relaxation dynamics for states within the hysteresis region compared with those outside of this region". Here we present a computer simulation study on cylindrical pores. We determine the adsorption isotherm, i.e., a steady state property, and the uptake dynamics inside and outside of the hysteresis loop. Further, we study the behavior during incomplete passage through the hysteresis loop, a situation which has been characterized recently by PFG NMR (pulsed field gradient nuclear magnetic resonance) and again has motivated elaborate explanations (Naumov et al. 2008). It is noteworthy that all experimental observations are reproduced when describing diffusion by the Onsager ansatz which employs the gradient of the chemical potential as driving force. No ad hoc assumptions about a new transport mechanism inside the hysteresis region are needed. © 2010 American Chemical Society.


Adams V.,University of Leipzig | Niebauer J.,Paracelsus Medical University
Heart Failure Clinics | Year: 2015

Until the late 1980s, physical exercise training was a contraindication in patients with heart failure. Extensive research has demonstrated that exercise training reverses heart failure-associated pathology at the clinical and molecular levels. Exercise training has emerged as a class I recommendation in all major national and international guidelines for the treatment of chronic heart failure. Knowledge gained in clinical trials and molecular research builds a strong case for exercise training as a key therapeutic component of an evidence-based treatment of chronic heart failure. It is long overdue to provide patients with an infrastructure that enables them to benefit from this class I intervention. © 2015 Elsevier Inc.


Wessel D.L.,Childrens National Medical Center | Berger F.,German Heart Institute Berlin | Li J.S.,Duke Clinical Research Institute | Dahnert I.,University of Leipzig | And 4 more authors.
New England Journal of Medicine | Year: 2013

BACKGROUND: Infants with cyanotic congenital heart disease palliated with placement of a systemic-to-pulmonary-artery shunt are at risk for shunt thrombosis and death. We investigated whether the addition of clopidogrel to conventional therapy reduces mortality from any cause and morbidity related to the shunt. METHODS: In a multicenter, double-blind, event-driven trial, we randomly assigned infants 92 days of age or younger with cyanotic congenital heart disease and a systemic-to-pul-monary-artery shunt to receive clopidogrel at a dose of 0.2 mg per kilogram of body weight per day (467 infants) or placebo (439 infants), in addition to conventional therapy (including aspirin in 87.9% of infants). The primary efficacy end point was a composite of death or heart transplantation, shunt thrombosis, or performance of a cardiac procedure due to an event considered to be thrombotic in nature before 120 days of age. RESULTS: The rate of the composite primary end point did not differ significantly between the clopidogrel group (19.1%) and the placebo group (20.5%) (absolute risk difference, 1.4 percentage points; relative risk reduction with clopidogrel, 11.1%; 95% confidence interval, -19.2 to 33.6; P = 0.43), nor did the rates of the three components of the composite primary end point. There was no significant benefit of clopidogrel treatment in any subgroup, including subgroups defined by shunt type. Clopidogrel recipients and placebo recipients had similar rates of overall bleeding (18.8% and 20.2%, respectively) and severe bleeding (4.1% and 3.4%, respectively). CONCLUSIONS: Clopidogrel therapy in infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary-artery shunt, most of whom received concomitant aspirin therapy, did not reduce either mortality from any cause or shunt-related morbidity. (Funded by Sanofi-Aventis and Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00396877.) Copyright © 2013 Massachusetts Medical Society.


Klein A.A.,Papworth Hospital | Skubas N.J.,New York Medical College | Ender J.,University of Leipzig
Anesthesia and Analgesia | Year: 2014

Transcatheter aortic valve replacement (TAVR) is performed with increasing frequency in the United States since Food and Drug Administration approval in 2011. The procedure involves the replacement of a severely stenosed native or bioprosthetic aortic valve with a specially constructed valvular prosthesis that is mounted onto a stent, without the use of cardiopulmonary bypass and the complications of a major open surgical procedure. TAVR has been performed mostly in elderly patients with multiple comorbidities or who have undergone previous cardiac surgery. The most commonly used access routes are the femoral artery (transfemoral) or the cardiac apex (transapical), but the transaortic and transubclavian approaches are also used with varying frequency. Conscious sedation may be used in patients undergoing transfemoral TAVR, but the use of general anesthesia has not been shown to carry greater risk and permits the use of transesophageal echocardiography to assist in valve positioning and diagnose complications. Cardiovascular instability during TAVR is relatively common, necessitating invasive monitoring and frequent use of vasoactive medications. Complications of the procedure are still relatively common and the most frequent is vascular injury to the access sites or the aorta. Cardiovascular collapse may be the result of major hemorrhage pericardial effusion with tamponade or coronary occlusion due to incorrect valve placement. Persistent hypotension, myocardial stunning, or injury requiring open surgical intervention may necessitate the use of cardiopulmonary bypass, the facilities for which should always be immediately available. Ongoing and planned trials comparing conventional surgery with TAVR in lower risk and younger patients should determine the place of TAVR in the medium-to long-term future. © 2014 International Anesthesia Research Society.


This is the first of a 2-part study on the history of psychiatry in Eastern Germany, i. e. the Soviet Occupied Zone and later German Democratic Republic. It mainly covers the years post World War II up until the beginning of the 1970s. The first post-war years were determined by the new power holders' attempts to overcome National Socialist (Nazi) heritage and to re-organize mental health and care in general. The doctrine of a strict denazifization in East Germany must, however, be regarded as a myth. Promoted by centralized organization, there was an increase in communist party-ideological influence and harassment as well as aligning scientific views and research with Soviet paradigms (Pavlovization) during the 1950s and early 1960s. This, however, led to an enormous rise in exodus of skilled labor to West Germany, which in turn further increased the notorious lack of staff. After the erection of the inner-German wall, this problem was mitigated, yet never fully solved over the 40 years of the existence of the GDR. Despite adverse conditions, East German psychiatrists made major original contributions to the development of psychiatry in general, at least up until the 1960s. Academic psychiatry was mainly based on biological concepts that were further promoted by new somatic and psychopharmacological therapeutic options. In the 1960s, social psychiatric reformist forces emerged, primarily in the large psychiatric hospitals. The improvements achieved by these forces, however, were not implemented on a nation-wide scale, but mainly restricted to one particular or several institutions. © Georg Thieme Verlag KG.


Sippel S.R.,University of Leipzig
Journal of Peasant Studies | Year: 2015

Worldwide investments in agricultural land have gained much attention in recent years, resulting in renewed awareness of land as being a scarce and finite resource. This paper investigates a case of South-to-North land deals, namely investments from the Arab Gulf targeting agricultural land in Australia. For the Arab Gulf States that highly depend on external food supplies, investment abroad is one strategy to guarantee future food security. At the same time, leading Australian political and economic representatives have been eager to attract investments from the Gulf. Increasing foreign investment in Australian land has, however, provoked a vivid public debate in Australia. Concepts of foreign direct investment and its role are currently renegotiated on the federal level with regard to Australia's own food security, the ‘national interest’ and the redefinition of ‘Australian agricultural land’. While these concerns also play out on the local level, investments have to be seen within the wider context of Australian ruralities. The paper reveals how food security and commercial and financial interests intersect and become blurred within current transformations of the global agri-food system. © 2015 Taylor & Francis.


Mierke C.T.,University of Leipzig | Frey B.,Friedrich - Alexander - University, Erlangen - Nuremberg | Fellner M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Herrmann M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Fabry B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Cell Science | Year: 2011

Cell migration through connective tissue, or cell invasion, is a fundamental biomechanical process during metastasis formation. Cell invasion usually requires cell adhesion to the extracellular matrix through integrins. In some tumors, increased integrin expression is associated with increased malignancy and metastasis formation. Here, we have studied the invasion of cancer cells with different α5β1 integrin expression levels into loose and dense 3D collagen fiber matrices. Using a cell sorter, we isolated from parental MDA-MB-231 breast cancer cells two subcell lines expressing either high or low amounts of α5β1 integrins (α5β1 high or α5β1low cells, respectively). α5β1high cells showed threefold increased cell invasiveness compared to α5β1low cells. Similar results were obtained for 786-O kidney and T24 bladder carcinoma cells, and cells in which the α5 integrin subunit was knocked down using specific siRNA. Knockdown of the collagen receptor integrin subunit α2 also reduced invasiveness, but to a lesser degree than knockdown of integrin subunit α5. Fourier transform traction microscopy revealed that the α5β1high cells generated sevenfold greater contractile forces than α5β1low cells. Cell invasiveness was reduced after addition of the myosin light chain kinase inhibitor ML-7 in α5β1high cells, but not in α5β1low cells, suggesting that α5β1 integrins enhance cell invasion through enhanced transmission and generation of contractile forces.


Hellwig C.T.,University of Leipzig | Hellwig C.T.,Royal College of Surgeons in Ireland | Rehm M.,Royal College of Surgeons in Ireland
Molecular Cancer Therapeutics | Year: 2012

TRAIL and agonistic antibodies raised against TRAIL death receptors are highly promising new anticancer agents. In this brief review, we describe the recent advances in the molecular understanding of TRAIL signaling and the progress made in using TRAIL or agonistic antibodies clinically in mono- and combination therapies. Synergies have been reported in various scenarios of TRAIL-based multidrug treatments, and these can be used to potentiate the efficacy of therapies targeting TRAIL death receptors. We pay particular attention to structure the current knowledge on the diverse molecular mechanisms that are thought to give rise to these synergies and describe how different signaling features evoking synergies can be associated with distinct classes of drugs used in TRAIL-based combination treatments. ©2012 AACR.


The T box riboswitch controls bacterial transcription by structurally responding to tRNA aminoacylation charging ratios. Knowledge of the thermodynamic stability difference between two competing structural elements within the riboswitch, the terminator and the antiterminator, is critical for effective T box-targeted drug discovery. The ΔG of aminoacyl tRNA synthetase (aaRS) T box riboswitch terminators and antiterminators was predicted using DINAMelt and the resulting ΔΔG (ΔG Terminator - ΔG Antiterminator) values were compared. Average ΔΔG values did not differ significantly between the bacterial species analyzed, but there were significant differences based on the type of aaRS. The data indicate that, of the bacteria studied, there is little potential for drug targeting based on overall bacteria-specific thermodynamic differences of the T box antiterminator vs. terminator stability, but that aaRS-specific thermodynamic differences could possibly be exploited for designing drug specificity.


von Laberg C.,University of Leipzig
PloS one | Year: 2014

Using state-of-the-art technology, interactions of eye, head and intersegmental body movements were analyzed for the first time during multiple twisting somersaults of high-level gymnasts. With this aim, we used a unique combination of a 16-channel infrared kinemetric system; a three-dimensional video kinemetric system; wireless electromyography; and a specialized wireless sport-video-oculography system, which was able to capture and calculate precise oculomotor data under conditions of rapid multiaxial acceleration. All data were synchronized and integrated in a multimodal software tool for three-dimensional analysis. During specific phases of the recorded movements, a previously unknown eye-head-body interaction was observed. The phenomenon was marked by a prolonged and complete suppression of gaze-stabilizing eye movements, in favor of a tight coupling with the head, spine and joint movements of the gymnasts. Potential reasons for these observations are discussed with regard to earlier findings and integrated within a functional model.


Conrad K.,TU Dresden | Roggenbuck D.,GA Generic Assays GmbH | Reinhold D.,Otto Von Guericke University of Magdeburg | Sack U.,University of Leipzig
Autoimmunity Reviews | Year: 2012

Disease associated autoantibodies (AAB) are important biomarkers not only to confirm the diagnosis of the respective systemic autoimmune disease but also to diagnose the disease at very early stages (mono- or oligosymptomatic manifestations) or to diagnose the respective disease without the typical clinical manifestations (atypical forms). A confirmation of the diagnosis in early stages is required, if patients should benefit from early therapeutic intervention. Furthermore, AAB determinations are used for prognostic purposes and for monitoring of disease activity or response to therapy. For the advancement of autoantibody diagnostics in clinical practice the following aspects have to be considered: (i) The search for novel clinically relevant AAB and the identification of autoantigenic targets of AAB broadened the spectrum of autoimmune diagnostics and permit the diagnosis of former idiopathic diseases. (ii) To obtain steady diagnostic variables of clinically relevant AAB, the evaluation studies have to be standardized. (iii) Several special features and novel developments of autoantibody diagnostics make correct interpretation of antibody test results increasingly difficult. (iv) Beside standardization of AAB detection methods and quality management efforts the improvement of autoantibody diagnostics depends on further development of diagnostic algorithms including cost-effective multiparametric analyses. © 2011 Elsevier B.V.


Schmidt H.,University of Leipzig
Frontiers in Molecular Neuroscience | Year: 2012

Many neurons of the vertebrate central nervous system (CNS) express the Ca 2+binding protein calbindin D-28k (CB), including important projection neurons like cerebellar Purkinje cells but also neocortical interneurons. CB has moderate cytoplasmic mobility and comprises at least four EF-hands that function in Ca 2+binding with rapid to intermediate kinetics and affinity. Classically it was viewed as a pure Ca 2+buffer important for neuronal survival. This view was extended by showing that CB is a critical determinant in the control of synaptic Ca 2+dynamics, presumably with strong impact on plasticity and information processing. Already 30 years ago, in vitro studies suggested that CB could have an additional Ca 2+sensor function, like its prominent acquaintance calmodulin (CaM). More recent work substantiated this hypothesis, revealing direct CB interactions with several target proteins. Different from a classical sensor, however, CB appears to interact with its targets both, in its Ca 2+-loaded and Ca 2+-free forms. Finally, CB has been shown to be involved in buffered transport of Ca 2+, in neurons but also in kidney. Thus, CB serves a threefold function as buffer, transporter and likely as a non-canonical sensor. © 2012 Schmidt.


Background:In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker.Methods:Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n=387) or placebo (n=387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis.Results:Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml-1) vs non-Asian patients (3193 pg ml-1), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml-1 increase: 1.19; 95% CI 1.10–1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13–1.64; P=0.0010 (Asians).Conclusions:Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.British Journal of Cancer advance online publication, 31 March 2016; doi:10.1038/bjc.2016.30 www.bjcancer.com. © 2016 Cancer Research UK


During the immune response, the cytokine interleukin 8 (IL-8, CXCL8) functions as a strong chemoattractant for polymorphonuclear leukocytes helping to direct these cells to infected/injured sites. This review focuses on the interaction of IL-8 with sulfated glycosaminoglycans expressed on cell surfaces and the extracellular matrix. This interaction contributes to the recruitment of polymorphonuclear cells from blood, penetration of these cells through the vessel wall, and their directed migration to inflammatory sites. Regulatory aspects of the interplay between IL-8 and heparan sulfate, the most abundant glycosaminoglycan, are highlighted. In this field, the large natural heterogeneity of glycosaminoglycans represents a great challenge that impedes the modeling of IL-8 functions. The interaction of IL-8 with newly developed artificial sulfated hyaluronan derivatives is also considered as these artificial substrates are an important tool for development of new materials in regenerative medicine.


Ahsanullah,Free University of Berlin | Rademann J.,University of Leipzig | Rademann J.,Leibniz Institute for Molecular Pharmacology
Angewandte Chemie - International Edition | Year: 2010

Support and guidance: Azidopeptidyl phosphoranes on a solid support react very efficiently through cyclative cleavage to yield cyclopeptides with an incorporated triazole ring. The solid support is advantageous as cyclization is favored strongly over oligomerization reactions and thus only cyclized products are released. "Chemical equation presented". © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.


Gross J.,Julich Research Center | Janke W.,University of Leipzig | Bachmann M.,Julich Research Center
Computer Physics Communications | Year: 2011

We discuss the advantages of parallelization by multithreading on graphics processing units (GPUs) for parallel tempering Monte Carlo computer simulations of an exemplified bead-spring model for homopolymers. Since the sampling of a large ensemble of conformations is a prerequisite for the precise estimation of statistical quantities such as typical indicators for conformational transitions like the peak structure of the specific heat, the advantage of a strong increase in performance of Monte Carlo simulations cannot be overestimated. Employing multithreading and utilizing the massive power of the large number of cores on GPUs, being available in modern but standard graphics cards, we find a rapid increase in efficiency when porting parts of the code from the central processing unit (CPU) to the GPU. © 2011 Elsevier B.V. All rights reserved.


The gram-positive thermophilic actinomycete Thermobifida fusca KW3 secretes a highly hydrophobic carboxylesterase (TfCa) that is able to hydrolyze poly(ethylene terephthalate). TfCa was produced in the Escherichia coli strain BL21(DE3) as a fusion protein consisting of a pelB leader sequence to ensure periplasmic localization of the protein and a His(6) tag for use in its purification. To enhance the recombinant enzyme yield, the tfca gene from T. fusca KW3 was successfully optimized for codon usage in E. coli. In addition, the gene expression induction conditions were optimized and the temperature for cell cultivation was lowered to reduce inclusion body formation. The optimized codons and expression conditions yielded 4500-fold higher TfCa activity than the wild-type strain. Using a pH-controlled bioreactor for cultivation, a TfCa protein concentration of 41.6mg/L was achieved.


Schade M.,Humboldt University of Berlin | Berti D.,University of Florence | Huster D.,University of Leipzig | Herrmann A.,Humboldt University of Berlin | Arbuzova A.,Humboldt University of Berlin
Advances in Colloid and Interface Science | Year: 2014

Lipophilic nucleic acids have become a versatile tool for structuring and functionalization of lipid bilayers and biological membranes as well as cargo vehicles to transport and deliver bioactive compounds, like interference RNA, into cells by taking advantage of reversible hybridization with complementary strands. This contribution reviews the different types of conjugates of lipophilic nucleic acids, and their physicochemical and self-assembly properties. Strategies for choosing a nucleic acid, lipophilic modification, and linker are discussed. Interaction with lipid membranes and its stability, dynamic structure and assembly of lipophilic nucleic acids upon embedding into biological membranes are specific points of the review. A large diversity of conjugates including lipophilic peptide nucleic acid and siRNA provides tailored solutions for specific applications in bio- and nanotechnology as well as in cell biology and medicine, as illustrated through some selected examples. © 2014 Elsevier B.V.


Hollands S.,University of Leipzig | Ishibashi A.,Kinki University
Communications in Mathematical Physics | Year: 2015

Recently, Durkee and Reall have conjectured a criterion for linear instability of rotating, extremal, asymptotically Minkowskian black holes in d≥4 dimensions, such as the Myers–Perry black holes. They considered a certain elliptic operator, A, acting on symmetric trace-free tensors intrinsic to the horizon. Based in part on numerical evidence, they suggested that if the lowest eigenvalue of this operator is less than the critical value −1/4 (called “effective BF-bound”), then the black hole is linearly unstable. In this paper, we prove an extended version of their conjecture. Our proof uses a combination of methods such as (1) the “canonical energy method” of Hollands–Wald, (2) algebraically special properties of the near horizon geometries associated with the black hole, (3) the Corvino–Schoen technique, and (4) semiclassical analysis. Our method of proof is also applicable to rotating, extremal asymptotically Anti-deSitter black holes. In that case, we find additional instabilities for ultra-spinning black holes. Although we explicitly discuss in this paper only extremal black holes, we argue that our results can be generalized to near extremal black holes. © 2015, Springer-Verlag Berlin Heidelberg.


Lehmann J.,University of Leipzig | Hitzler P.,Wright State University
Machine Learning | Year: 2010

With the advent of the Semantic Web, description logics have become one of the most prominent paradigms for knowledge representation and reasoning. Progress in research and applications, however, is constrained by the lack of well-structured knowledge bases consisting of a sophisticated schema and instance data adhering to this schema. It is paramount that suitable automated methods for their acquisition, maintenance, and evolution will be developed. In this paper, we provide a learning algorithm based on refinement operators for the description logic ALCQ including support for concrete roles. We develop the algorithm from thorough theoretical foundations by identifying possible abstract property combinations which refinement operators for description logics can have. Using these investigations as a basis, we derive a practically useful complete and proper refinement operator. The operator is then cast into a learning algorithm and evaluated using our implementation DL-Learner. The results of the evaluation show that our approach is superior to other learning approaches on description logics, and is competitive with established ILP systems.


Holland J.,Ecole Polytechnique - Palaiseau | Hollands S.,University of Leipzig
Communications in Mathematical Physics | Year: 2015

We derive a novel formula for the derivative of operator product expansion (OPE) coefficients with respect to a coupling constant. The formula involves just the OPE coefficients themselves but no further input, and is in this sense self-consistent. Furthermore, unlike other formal identities of this general nature in quantum field theory (such as the formal expression for the Lagrangian perturbation of a correlation function), our formula requires no further UV-renormalization, i.e., it is completely well-defined from the start. This feature is a result of a cancelation of UV- and IR-divergences between various terms in our identity. Our proof, and an analysis of the features of the identity, is given for the example of massive, Euclidean φ4 theory in 4 dimensional Euclidean space. It relies on the renormalization group flow equation method and is valid to arbitrary, but finite orders in perturbation theory. The final formula, however, makes neither explicit reference to the renormalization group flow, nor to perturbation theory, and we conjecture that it also holds non-perturbatively. Our identity can be applied constructively because it gives a novel recursive algorithm for the computation of OPE coefficients to arbitrary (finite) perturbation order in terms of the zeroth order coefficients corresponding to the underlying free field theory, which in turn are trivial to obtain. We briefly illustrate the relation of this method to more standard methods for computing the OPE in some simple examples. © 2015, Springer-Verlag Berlin Heidelberg.


Meusinger H.,Thuringer Landessternwarte Tautenburg | Balafkan N.,University of Leipzig
Astronomy and Astrophysics | Year: 2014

Aims. A tiny fraction of the quasar population shows remarkably weak emission lines. Several hypotheses have been developed, but the weak line quasar (WLQ) phenomenon still remains puzzling. The aim of this study was to create a sizeable sample of WLQs and WLQ-like objects and to evaluate various properties of this sample. Methods. We performed a search for WLQs in the spectroscopic data from the Sloan Digital Sky Survey Data Release 7 based on Kohonen self-organising maps for nearly 105 quasar spectra. The final sample consists of 365 quasars in the redshift range z = 0.6 - 4.2 (z = 1.50 ± 0.45) and includes in particular a subsample of 46 WLQs with equivalent widths WMg ii< 11 Å and WC iv< 4.8 Å. We compared the luminosities, black hole masses, Eddington ratios, accretion rates, variability, spectral slopes, and radio properties of the WLQs with those of control samples of ordinary quasars. Particular attention was paid to selection effects. Results. The WLQs have, on average, significantly higher luminosities, Eddington ratios, and accretion rates. About half of the excess comes from a selection bias, but an intrinsic excess remains probably caused primarily by higher accretion rates. The spectral energy distribution shows a bluer continuum at rest-frame wavelengths 1500 Å. The variability in the optical and UV is relatively low, even taking the variability-luminosity anti-correlation into account. The percentage of radio detected quasars and of core-dominant radio sources is significantly higher than for the control sample, whereas the mean radio-loudness is lower. Conclusions. The properties of our WLQ sample can be consistently understood assuming that it consists of a mix of quasars at the beginning of a stage of increased accretion activity and of beamed radio-quiet quasars. The higher luminosities and Eddington ratios in combination with a bluer spectral energy distribution can be explained by hotter continua, i.e. higher accretion rates. If quasar activity consists of subphases with different accretion rates, a change towards a higher rate is probably accompanied by an only slow development of the broad line region. The composite WLQ spectrum can be reasonably matched by the ordinary quasar composite where the continuum has been replaced by that of a hotter disk. A similar effect can be achieved by an additional power-law component in relativistically boosted radio-quiet quasars, which may explain the high percentage of radio quasars. © 2014 ESO.


Sanders K.,University of Leipzig
Letters in Mathematical Physics | Year: 2015

We consider a linear scalar quantum field propagating in a spacetime of dimension d ≥ 2 with a static bifurcate Killing horizon and a wedge reflection. Under suitable conditions (e.g. positive mass), we prove the existence of a pure Hadamard state which is quasi-free, invariant under the Killing flow and restricts to a double βH-KMS state on the union of the exterior wedge regions, where βH is the inverse Hawking temperature. The existence of such a state was first conjectured by Hartle and Hawking (Phys Rev D 13:2188–2203, 1976) and by Israel (Phys Lett 57:107–110, 1976), in the more general case of a stationary black hole spacetime. Jacobson (Phys Rev D 50:R6031–R6032, 1994) has conjectured a similar state to exist even for interacting fields in spacetimes with a static bifurcate Killing horizon. The state can serve as a ground state on the entire spacetime and the resulting situation generalises that of the Unruh effect in Minkowski spacetime. Our result complements a well-known uniqueness result of Kay and Wald (Phys Rep 207:49–136, 1991) and Kay (J Math Phys 34:4519–4539, 1993), who considered a general bifurcate Killing horizon and proved that a certain (large) subalgebra of the free field admits at most one Hadamard state which is invariant under the Killing flow. This state is pure and quasi-free and in the presence of a wedge reflection it restricts to a βH-KMS state on the smaller subalgebra associated to one of the exterior wedge regions. Our result establishes the existence of such a state on the full algebra, but only in the static case. Our proof follows the arguments of Sewell (Ann Phys 141: 201–224, 1982) and Jacobson (Phys Rev D 50:R6031–R6032, 1994), who exploited a Wick rotation in the Killing time coordinate to construct a corresponding Euclidean theory. In particular, we show that for the linear scalar field we can recover a Lorentzian theory by Wick rotating back. Because the Killing time coordinate is ill-defined on the bifurcation surface, we systematically replace it by a Gaussian normal coordinate. A crucial part of our proof is to establish that the Euclidean ground state satisfies the necessary analogues of analyticity and reflection positivity with respect to this coordinate. © 2015, Springer Science+Business Media Dordrecht.


Hoehndorf R.,University of Cambridge | Harris M.A.,University of Cambridge | Herre H.,University of Leipzig | Rustici G.,European Bioinformatics Institute | Gkoutos G.V.,University of Cambridge
Bioinformatics | Year: 2012

Motivation: The systematic observation of phenotypes has become a crucial tool of functional genomics, and several large international projects are currently underway to identify and characterize the phenotypes that are associated with genotypes in several species. To integrate phenotype descriptions within and across species, phenotype ontologies have been developed. Applying ontologies to unify phenotype descriptions in the domain of physiology has been a particular challenge due to the high complexity of the underlying domain. Results: In this study, we present the outline of a theory and its implementation for an ontology of physiology-related phenotypes. We provide a formal description of process attributes and relate them to the attributes of their temporal parts and participants. We apply our theory to create the Cellular Phenotype Ontology (CPO). The CPO is an ontology of morphological and physiological phenotypic characteristics of cells, cell components and cellular processes. Its prime application is to provide terms and uniform definition patterns for the annotation of cellular phenotypes. The CPO can be used for the annotation of observed abnormalities in domains, such as systems microscopy, in which cellular abnormalities are observed and for which no phenotype ontology has been created. © The Author 2012. Published by Oxford University Press. All rights reserved.


Five new coordination polymers, [Mn(DPA)(Me4bpz)( H2O)](I)1, [Cu(DPA)(Me4bpz)2] ·H2O(II)1 [Ag4(OAc)2( Me4bpz)3(H2O)1.56](III) 2, [Zn(DPA)(Me4bpz)]·0.61H2O(IV) 3 and [Cd(DPA)(Me4bpz)](V)3[DPA: diphenic acid dianion, OAc: acetate, Me4bpz: 3,3′,5,5′-tetramethyl-4, 4′-bipyrazole], were obtained from acetate hydrates of Mn2+, Cu2+, Ag+, Zn2+ and Cd2+ and a mixed ligand system consisting of Me4bpz and diphenic acid by hydrothermal synthesis under similar conditions. Their crystal structures were determined by means of X-ray single crystal structure analysis. Furthermore, the compounds were characterized by means of elemental analysis and IR spectroscopy. The polymers I and II exhibit one-dimensional chain structures with only one type of bridging ligand, whereas the polymers IV and V realize three-dimensional coordination frameworks with diamond topology involving both ligand types as bridging ligands. Compound III contains a two-dimensional cationic framework which is charge compensated by acetate anions. The coordination environments of the metal centers are predominant directly supported by N-H ⋯ O hydrogen bonds providing further evidence for the bipyrazole-carboxylate supramolecular synthon.© 2012 Elsevier B.V. All rights reserved.


Laue R.,University of Leipzig | Awad A.,University of Potsdam
Journal of Visual Languages and Computing | Year: 2011

Business processes are commonly modeled using a graphical modeling language. The most widespread notation for this purpose is business process diagrams in the Business Process Modeling Notation (BPMN). In this article, we use the visual query language BPMN-Q for expressing patterns that are related to possible problems in such business process diagrams. We discuss two classes of problems that can be found frequently in real-world models: sequence flow errors and model fragments that can make the model difficult to understand.By using a query processor, a business process modeler is able to identify possible errors in business process diagrams. Moreover, the erroneous parts of the business process diagram can be highlighted when an instance of an error pattern is found. This way, the modeler gets an easy-to-understand feedback in the visual modeling language he or she is familiar with. This is an advantage over current validation methods, which usually lack this kind of intuitive feedback. © 2011 Elsevier Ltd.


Bohlig L.,University of Leipzig | Rother K.,Saarland University
Journal of Biomedicine and Biotechnology | Year: 2011

Maintenance of genome integrity is a dynamic process involving complex regulation systems. Defects in one or more of these pathways could result in cancer. The most important tumor-suppressor is the transcription factor p53, and its functional inactivation is frequently observed in many tumor types. The tumor suppressive function of p53 is mainly attributed to its ability to regulate numerous target genes at the transcriptional level. While the mechanism of transcriptional induction by p53 is well characterized, p53-dependent repression is not understood in detail. Here, we review the manifold mechanisms of p53 as a transcriptional repressor. We classify two different categories of repressed genes based on the underlying mechanism, and novel mechanisms which involve regulation through noncoding RNAs are discussed. The complete elucidation of p53 functions is important for our understanding of its tumor-suppressor activity and, therefore, represents the key for the development of novel therapeutic approaches. Copyright 2011 Levin Bhlig and Karen Rother.


Algergawy A.,University of Leipzig | Nayak R.,Queensland University of Technology | Saake G.,Otto Von Guericke University of Magdeburg
Information Sciences | Year: 2010

Schema matching plays a central role in a myriad of XML-based applications. There has been a growing need for developing high-performance matching systems in order to identify and discover semantic correspondences across XML data. XML schema matching methods face several challenges in the form of definition, adoption, utilization, and combination of element similarity measures. In this paper, we classify, review, and experimentally compare major methods of element similarity measures and their combinations. We aim at presenting a unified view which is useful when developing a new element similarity measure, when implementing an XML schema matching component, when using an XML schema matching system, and when comparing XML schema matching systems. © 2010 Elsevier Inc. All rights reserved.


Raz R.,Leibniz Institute for Molecular Pharmacology | Raz R.,Free University of Berlin | Rademann J.,University of Leipzig | Rademann J.,Leibniz Institute for Molecular Pharmacology
Organic Letters | Year: 2011

tert-Butyl thioesters display an astonishing stability toward secondary amines in basic milieu, in contrast to other alkyl and aryl thioesters. Exploiting this enhanced stability, peptide thioesters were synthesized in a direct manner, applying a tert-butyl thiol linker for Fmoc-based solid-phase peptide synthesis. © 2011 American Chemical Society.


Droste M.,University of Leipzig | Stuber T.,TU Dresden | Vogler H.,TU Dresden
Information Sciences | Year: 2010

We investigate weighted finite automata over strings and strong bimonoids. Such algebraic structures satisfy the same laws as semirings except that no distributivity laws need to hold. We define two different behaviors and prove precise characterizations for them if the underlying strong bimonoid satisfies local finiteness conditions. Moreover, we show that in this case the given weighted automata can be determinized. © 2009 Elsevier Inc. All rights reserved.


Bader A.,University of Leipzig | Macchiarini P.,University of Florence
Journal of Cellular and Molecular Medicine | Year: 2010

In June 2008, the world's first whole tissue-engineered organ - the windpipe - was successfully transplanted into a 31-year-old lady, and about 18 months following surgery she is leading a near normal life without immunosuppression. This outcome has been achieved by employing three groundbreaking technologies of regenerative medicine: (i) a donor trachea first decellularized using a detergent (without denaturing the collagenous matrix), (ii) the two main autologous tracheal cells, namely mesenchymal stem cell derived cartilage-like cells and epithelial respiratory cells and (iii) a specifically designed bioreactor that reseed, before implantation, the in vitro pre-expanded and pre-differentiated autologous cells on the desired surfaces of the decellularized matrix. Given the long-term safety, efficacy and efforts using such a conventional approach and the potential advantages of regenerative implants to make them available for anyone, we have investigated a novel alternative concept how to fully avoid in vitro cell replication, expansion and differentiation, use the human native site as micro-niche, potentiate the human body's site-specific response by adding boosting, permissive and recruitment impulses in full respect of sociological and regulatory prerequisites. This tissue-engineered approach and ongoing research in airway transplantation is reviewed and presented here. © 2010 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.


Kirschner R.,University of Leipzig
Journal of Physics: Conference Series | Year: 2013

The restiction to the class of Jordan - Schwinger representations of sℓ(n + 1) results in simple relations for the L matrices and in explicit expressions for the general Yang-Baxter operators as products of two parameter permutation operators. Limits are studied which are related to the finite dimensional representations and to degenerate Yangians. The analogy to the sℓ(2) case leads to analogous forms of global spin chain operators. © Published under licence by IOP Publishing Ltd.


Claussen I.,University of Gottingen | Brand R.A.,Karlsruhe Institute of Technology | Hahn H.,Karlsruhe Institute of Technology | Mayr S.G.,University of Leipzig
Scripta Materialia | Year: 2012

Fe-Pd-based ferromagnetic shape memory alloys are based on metastable random solid solutions in the austenite and martensite phases, which require preparation from the equilibrium γ phase by rapid cooling. Employing splats, we explore the impact of annealing treatment on the disordered solid solution, phase formation and lattice defects using a combined conversion electron Mössbauer spectroscopy - X-ray diffraction study. We discuss indications of short range ordering tendencies as well as the impact of splat microstructure and defects on phase formation. © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Klimchitskaya G.L.,North West Technical University | Bordag M.,University of Leipzig | Mostepanenko V.M.,Noncommercial Partnership Scientific Instruments
International Journal of Modern Physics A | Year: 2012

We analyze recent experiments on measuring the thermal Casimir force with account of possible background effects. Special attention is paid to the validity of the proximity force approximation (PFA) used in the comparison between the experimental data and computational results in experiments employing a sphere-plate geometry. The PFA results are compared with the exact results where they are available. The possibility to use fitting procedures in theory-experiment comparison is discussed. On this basis we reconsider experiments exploiting spherical lenses of centimeter-size radii. © 2012 World Scientific Publishing Company.


Thor A.,University of Leipzig | Bornmann L.,ETH Zurich
Online Information Review | Year: 2011

Purpose - The single publication h index has been introduced by Schubert as the h index calculated from the list of citing publications of one single publication. This paper aims to look at the calculation of the single publication h index and related performance measures. Design/methodology/ approach - In this paper a web application is presented where the single publication h index and related performance measures (the single publication m index, h 2 lower, h 2 centre, and h 2 upper) can be automatically calculated for any publication indexed by Google Scholar. Findings - The use of the application is demonstrated by means of the citation performance of two publications. Originality/value - To the authors' knowledge this web application is the first instrument to automatically calculate the single publication h index and related performance measures based on Google Scholar data. This is a new service especially from the perspective of the related performance measures. © Emerald Group Publishing Limited.


Singer S.,University of Mainz | Singer S.,University of Leipzig | Dieng S.,OnkoZert | Wesselmann S.,German Cancer Society
Psycho-Oncology | Year: 2013

Background Over the last few years, a nationwide voluntary certification system for cancer centres has been established in Germany. To qualify for certification, cancer centres must provide psycho-oncological care to every patient who needs it. The aim of this study was to find out how many patients have been treated by a psycho-oncologist in the certified centres. Methods All cancer centres in Germany that were re-certified in 2010 provided data documenting how many patients with primary cancer received at least 30 min of psycho-oncological consultation in 2009. Results Data from n = 456 certified cancer centres were available. In the centres, a total of 36 165 patients were seen by a psycho-oncologist for at least 30 min, representing 37.3% of all patients in the centres. The highest percentage of patients who received psycho-oncological care was found in breast cancer centres (66.7%), and the lowest in prostate cancer centres (6.8%). Half of the patients (50.0%) in gynaecological cancer centres, 37.7% in colon cancer centres and 25.4% in lung cancer centres received psycho-oncological care. Conclusions Compared with non-certified centres, the proportion of patients receiving psycho-oncological care in certified cancer centres has increased. Copyright © 2012 John Wiley & Sons, Ltd.


Bernstein P.A.,Microsoft | Madhavan J.,Google | Rahm E.,University of Leipzig
Proceedings of the VLDB Endowment | Year: 2011

In a paper published in the 2001 VLDB Conference, we proposed treating generic schema matching as an independent problem. We developed a taxonomy of existing techniques, a new schema matching algorithm, and an approach to comparative evaluation. Since then, the field has grown into a major research topic. We briefly summarize the new techniques that have been developed and applications of the techniques in the commercial world. We conclude by discussing future trends and recommendations for further work. © 2011 VLDB Endowment.


In the present work a systematic investigation of temperature on the dynamic structure of water and noble gases is given and a simple formula for the temperature dependent distribution functions with two terms is gained. The singular value decomposition tool is applied to temperature dependent radial and spatial distribution functions to decompose them into linear combinations of distant dependent grund radial/spatial distribution functions gi(r) and temperature dependent coefficients ci(T). The method condenses information from a large amount of data into a much smaller and manageable amount without loss of information. For the test systems (TIP3P water and noble gases with different force fields), the main temperature changes are condensed into the second grund function g2 and its coefficient c2. c2 obeys the Boltzmann distribution law and altogether we find thatgrT≈gcr+e-DR×T×gtrin a temperature range of more than 700 K. We introduce the new property of the thermal stability and the thermal stability energy D. This single energy and the grund functions characterize the structural changes (e.g., hydrogen bonds) in liquids from ambient temperatures up to supercritical states. © 2013 Elsevier B.V.


Emmerich I.U.,University of Leipzig
Tierarztliche Praxis Ausgabe K: Kleintiere - Heimtiere | Year: 2012

In 2011, nine active pharmaceutical ingredients were released on the German market for small animals. Those are the cyclooxygenase-2-inhibitor Cimicoxib (Cimalgex®), the opium-derived analgesic Methadone (Comfortan®), the antiemetic Metoclopramide (Emeprid®), the corticosteroid Mometasone furoate in combination with the antifungal agent Posaconazole (Posatex®), the fluorchinolone-antibiotic Pradofloxacin (Veraflox®), the insecticide Spinosad (Comfortis®), the cytostatic Toceranib (Palladia®) and the vitamin Phytomenadione (Vitamin K1 Laboratoire TVM). Two additional substances were authorized for additional species. The tetracycline-antibiotic Doxycycline is now available for carrier pigeons and the anticoccidial Toltrazuril in combination with Emodepside is likewise authorized for dogs. Furthermore, one new preparation with an interesting new pharmaceutical form and two products with a new strength were added to the market for small animals. In addition, four active pharmaceutical ingredients with approval for use in human medicine, which are of potential interest to veterinary medicine, entered the market in 2011. Those are the antiepileptic Retigabine, the ophthalmic Bromfenac, the psychotropic drug Dexamfetamine and the cytostatic Eribulin. © Schattauer 2012.


Wilhelm C.,University of Leipzig | Selmar D.,TU Braunschweig
Journal of Plant Physiology | Year: 2011

In bright sunlight photosynthetic activity is limited by the enzymatic machinery of carbon dioxide assimilation. This supererogation of energy can be easily visualized by the significant increases of photosynthetic activity under high CO2 conditions or other metabolic strategies which can increase the carbon flux from CO2 to metabolic pools. However, even under optimal CO2 conditions plants will provide much more NADPH+H+ and ATP that are required for the actual demand, yielding in a metabolic situation, in which no reducible NADP+ would be available. As a consequence, excited chlorophylls can activate oxygen to its singlet state or the photosynthetic electrons can be transferred to oxygen, producing highly active oxygen species such as the superoxide anion, hydroxyl radicals and hydrogen peroxide. All of them can initiate radical chain reactions which degrade proteins, pigments, lipids and nucleotides. Therefore, the plants have developed protection and repair mechanism to prevent photodamage and to maintain the physiological integrity of metabolic apparatus. The first protection wall is regulatory energy dissipation on the level of the photosynthetic primary reactions by the so-called non-photochemical quenching. This dissipative pathway is under the control of the proton gradient generated by the electron flow and the xanthophyll cycle. A second protection mechanism is the effective re-oxidation of the reduction equivalents by so-called " alternative electron cycling" which includes the water-water cycle, the photorespiration, the malate valve and the action of antioxidants. The third system of defence is the repair of damaged components. Therefore, plants do not suffer from energy shortage, but instead they have to invest in proteins and cellular components which protect the plants from potential damage by the supererogation of energy. Under this premise, our understanding and evaluation for certain energy dissipating processes such as non-photochemical quenching or photorespiration appear in a quite new perspective, especially when discussing strategies to improve the solar energy conversion into plant biomass. © 2010 Elsevier GmbH.


Mierke C.T.,University of Leipzig | Mierke C.T.,Friedrich - Alexander - University, Erlangen - Nuremberg
Molecular BioSystems | Year: 2012

Most cancer-related deaths are caused by the ability of cancer cells to metastasize. This process includes the dissemination of cancer cells from the primary tumor side and their migration to targeted organ sites. During the migration of cancer cells through the connective tissue microenvironment, which consists of endothelial cells and extracellular matrix components, biomechanical properties are crucial for the efficiency and speed of cancer cell invasion and subsequently, metastases formation. Biomechanics can enable cancer cells to migrate through tissue, transmigrate through basement membranes as well as endothelial monolayers and form metastases in targeted organs. The current focus of cancer research still lies on the investigation of cancer cell's biochemical and molecular capabilities such as molecular genetics and gene signaling, but these approaches ignore the mechanical nature of the invasion process of cancer cells. Moreover, even the role of the endothelium during the transmigration and invasion of cells is not clear, it has been seen as a passive barrier, but this could not explain all novel findings. This review discusses how cancer cells alter the structural, biochemical and mechanical properties of the endothelium to regulate their own invasiveness through extracellular matrices and hence, through the tissue microenvironment. Finally, this review sheds light on the mechanical properties of cancer cells and the interacting endothelium and points out the importance of the mechanical properties as a critical determinant for the efficiency of cancer cell invasion and the overall progression of cancer. In conclusion, the regulation of the endothelial cell's biomechanical properties by cancer cells is a critical determinant of cancer cell invasiveness and may affect the future development of new cancer treatments. © 2012 The Royal Society of Chemistry.


Strass H.,University of Leipzig
Journal of Artificial Intelligence Research | Year: 2015

We analyse the expressiveness of Brewka and Woltran's abstract dialectical frameworks for two-valued semantics. By expressiveness we mean the ability to encode a desired set of two-valued interpretations over a given propositional vocabulary A using only atoms from A. We also compare ADFs' expressiveness with that of (the two-valued semantics of) abstract argumentation frameworks, normal logic programs and propositional logic. While the computational complexity of the two-valued model existence problem for all these languages is (almost) the same, we show that the languages form a neat hierarchy with respect to their expressiveness. We then demonstrate that this hierarchy collapses once we allow to introduce a linear number of new vocabulary elements. We finally also analyse and compare the representational succinctness of ADFs (for two-valued model semantics), that is, their capability to represent two-valued interpretation sets in a space-Efficient manner. © 2015 AI Access Foundation. All rights reserved.


Baader F.,TU Dresden | Pealoza R.,University of Leipzig
Journal of Logic and Computation | Year: 2010

Axiom pinpointing has been introduced in description logics (DLs) to help the user to understand the reasons why consequences hold and to remove unwanted consequences by computing minimal (maximal) subsets of the knowledge base that have (do not have) the consequence in question. Most of the pinpointing algorithms described in the DLliterature are obtained as extensions of the standard tableau-based reasoning algorithms for computing consequences from DL knowledge bases. Although these extensions are based on similar ideas, they are all introduced for a particular tableau-based algorithm for a particular DL. The purpose of this article is to develop a general approach for extending a tableau-based algorithm to a pinpointing algorithm. This approach is based on a general definition of 'tableau algorithms,' which captures many of the known tableau-based algorithms employed in DLs, but also other kinds of reasoning procedures.


As the sequential inflammatory changes are the same in erythema elevatum diutinum (EED) and granuloma faciale (GF), histopathologic distinction may be difficult. All available cases from 1998 to 2009 with the diagnosis of EED and GF were collected and reviewed, both clinically and histopathologically. Nine cases of EED and 41 cases of GF were reviewed in a blinded fashion using a checklist of 26 histopathologic criteria. Only four of the evaluated criteria showed differences between GF and EED. High density of the infiltrate was noted in 97% of cases of GF but only in 56% of cases of EED. Eosinophils were the predominant cell type in 59% of cases of GF but in none of the cases of EED. Plasma cells were more frequent in GF (64%) than in EED (22%), and granulomas were never found in GF but in 22% of EED. A zone of perijunctional sparing (Grenz zone) was observed in about three quarters of the cases in both the groups. The histopathology of GF and EED is very similar and overlapping. The presence of a Grenz zone and patterned fibrosis does not distinguish the two diseases. However, granulomatous nodules are only seen in EED, and a predominance of eosinophils in the infiltrate favors a diagnosis of GF. Copyright © 2011 John Wiley & Sons A/S.


Determination of blood IgE levels is routinely performed when investigating immediate-type allergies. Increased levels of total IgE may be seen in allergy but also in several other diseases, i.e. in hyper-IgE syndrome. Specific IgE shows sensitization to certain allergens, however, clinical relevance of this sensitization remains to be elucidated by carefully regarding patient's history, clinical symptoms and additional results from organ-specific provocation tests (i.e. food challenge). This paper gives a review of recent developments in IgE diagnostic methods (including bio-chip technology, component-resolved diagnostic, screening for cross-reacting carbohydrate determinants/CCDs and inhibition tests). Several case reports are presented to point out the usefulness of different diagnostics methods. Component-resolved diagnostic has shown to be very useful in food allergy (i.e. antibodies to rGly m 4 in birch-associated soy allergy, to rTri a 19 in wheat-induced anaphylaxis, Ara h 2 and Ara h 3 in severe reactions to peanuts) as well as in hymenoptera allergy (Api m 1, Ves v 5). © 2012 Dustri-Verlag Dr. Karl Feistle.


Richter D.,University of Leipzig | Kunzmann U.,University of Bamberg
Psychology and Aging | Year: 2011

This study investigated age differences in cognitive and affective facets of empathy: the ability to perceive another's emotions accurately, the capacity to share another's emotions, and the ability to behaviorally express sympathy in an empathic episode. Participants, 80 younger (Mage = 32 years) and 73 older (Mage = 59 years) adults, viewed eight film clips, each portraying a younger or an older adult thinking-aloud about an emotionally engaging topic that was relevant to either younger adults or older adults. In comparison to their younger counterparts, older adults generally reported and expressed greater sympathy while observing the target persons; and they were better able to share the emotions of the target persons who talked about a topic that was relevant to older adults. Age-related deficits in the cognitive ability to accurately perceive another's emotions were only evident when the target person talked about a topic of little relevance to older adults. In sum, the present performance-based evidence speaks for multidirectional age differences in empathy. © 2010 American Psychological Association.


Grussendorf M.,Endokrinologie und Diabetologie im Zentrum | Reiners C.,University of Wurzburg | Paschke R.,University of Leipzig | Wegscheider K.,University of Hamburg
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Context: Nodular goiter is common world wide, but there is still debate over the medical treatment. Objective: The objective of the study was the measurement of the effect of a treatment with (nonsuppressive) T 4, iodine, or a combination of both compared with placebo on volume of thyroid nodules and thyroid. Design: This was a multicenter, randomized, double-blind trial in patients with nodular goiter in Germany [LISA (Levothyroxin und Iodid in der Strumatherapie Als Mono-oder Kombinationstherapie) trial]. Setting: The study was conducted in outpatient clinics in university hospitals and regional hospitals and private practices. Participants: One thousand twenty-four consecutively screened and centrally randomized euthyroid patients aged 18-65 yr with one or more thyroid nodules (minimal diameter 10 mm) participated in the study. Intervention: Intervention included placebo, iodine (I), T 4, or T 4+I for 1 yr. T 4 doses were adapted for a TSH target range of 0.2- 0.8 mU/liter. Outcome Measures: The primary end point was percent volume reduction of all nodules measured by ultrasound, and the main secondary end point was a change in goiter volume. Results: Nodule volume reductions were -17.3% [95% confidence interval (CI) -24.8/-9.0%, P < 0.001] in the T 4+I group,-7.3% (95% CI-15.0/+1.2%, P = 0.201) in the T 4 group, and -4.0% (95% CI - 11.4/+4.2%, P = 0.328) in the I group as compared with placebo. In direct comparison, the T 4+I therapy was significantly superior to T 4 (P = 0.018) or I (P = 0.003). Thyroid volume reductions were -7.9% (95% CI - 11.8/-3.9%, P < 0.001), -5.2% (95% CI - 8.7/-1.6%, P = 0.024) and -2.5% (95% CI - 6.2/+1.4%, P = 0.207), respectively. The T 4+I therapy was significantly superior to I (P = 0.034) but not to T 4 (P = 0.190). Conclusion: In a region with a sufficient iodine supply, a 1-yr therapy with a combination of I and T4 with incomplete suppression of thyrotropin reduced thyroid nodule volume further than either component alone or placebo. Copyright © 2011 by The Endocrine Society.


An all-sky VHF meteor radar (MR) has been continuously operated at Collm (51.3° N, 13° E) since summer 2004. The radar measures meteor parameters, diffusion coefficients, and horizontal winds in the mesopause region. There exists a temporal overlap of the MR wind measurements with co-located low-frequency (LF) ionospheric drift measurements until 2007. Comparison of MR and LF semidiurnal tidal phases allows to empirically determine the virtual height overestimation of LF reflection heights due to the group retardation of LF waves. LF reference heights have to be reduced by up to 20 km to match real heights. Correction of LF heights for group retardation allows to determine the wind underestimation by the LF method compared with meteor radar measurements and opens the possibility to continue long-term trend analysis using mesosphere/lower thermosphere winds. © 2011 Author(s) CC Attribution 3.0 License.


Seaton D.T.,Massachusetts Institute of Technology | Schnabel S.,University of Leipzig | Landau D.P.,University of Georgia | Bachmann M.,University of Georgia
Physical Review Letters | Year: 2013

Inspired by recent studies revealing unexpected pliability of semiflexible biomolecules like RNA and DNA, we systematically investigate the range of structural phases by means of a simple generic polymer model. Using a two-dimensional variant of Wang-Landau sampling to explore the conformational space in energy and stiffness within a single simulation, we identify the entire diversity of structures existing from the well-studied limit of flexible polymers to that of wormlike chains. We also discuss, in detail, the influence of finite-size effects in the formation of crystalline structures that are virtually inaccessible via conventional computational approaches. © 2013 American Physical Society.


The pathophysiologic process of local tumor spread is regarded as an isotropic infiltration of microscopic extensions of the malignant lesion irrespective of tissue boundaries. By contrast, the ontogenetic compartment theory states that malignant solid tumors are locally confined, for a relatively long phase during their natural course, to a permissive compartment derived from a common primordium in embryonic development. Tumor permeation is isotropic within the permissive ontogenetic compartment, but it is suppressed at the compartment borders. The validity of the ontogenetic compartment theory has been shown for cancer of the rectum and of the female lower genital tract. It is hypothesized that ontogenetic compartment resection, the translation of the theory into cancer surgery, holds a great potential to improve oncologic treatment results. © 2012 Future Medicine Ltd.


Mangner N.,University of Leipzig
Medicine and Science in Sports and Exercise | Year: 2016

PURPOSE: Patient studies have demonstrated the efficacy of exercise training in attenuating respiratory muscle weakness in chronic heart failure (HF), yet direct assessment of muscle fiber contractile function together with data on the underlying intracellular mechanisms remain elusive. The present study, therefore, used a mouse model of HF to assess whether exercise training could prevent diaphragm contractile fiber dysfunction, by potentially mediating the complex interplay between intracellular oxidative stress and proteolysis. METHODS: Mice underwent sham operation (n=10) or a ligation of the left coronary artery and were randomized to sedentary HF (n=10) or HF with aerobic exercise training (HF+AET; n=10). Ten weeks later, echocardiography and histological analyses confirmed HF. RESULTS: In vitro diaphragm fiber bundles demonstrated contractile dysfunction in sedentary HF compared to sham mice that was prevented by AET, with maximal force 21.0±0.7 vs. 26.7±1.4 and 25.4±1.4 N/cm, respectively (P<0.05). Xanthine oxidase enzyme activity and MuRF1 protein expression, markers of oxidative stress and protein degradation, were ~20 and ~70 % higher in sedentary HF compared to sham mice (P<0.05), but were not different when compared to the HF+AET group. Oxidative modifications to numerous contractile proteins (i.e., actin and creatine kinase) and markers of proteolysis (i.e. proteasome and calpain activity) were elevated in sedentary HF compared to HF+AET mice (P<0.05), however these indices were not significantly different between sedentary HF and sham mice. Anti-oxidative enzyme activities were also not different between groups. CONCLUSION: Our findings demonstrate that aerobic exercise training can protect against diaphragm contractile fiber dysfunction induced by HF, but it remains unclear whether alterations in oxidative stress and/or protein degradation are primarily responsible. © 2016 American College of Sports Medicine


Bluher M.,University of Leipzig
Endocrine | Year: 2012

Vaspin (visceral adipose tissue-derived serpin; serpinA12) was originally identified as an adipokine, which is predominantly secreted from visceral adipose tissue in Otsuka Long-Evans Tokushima fatty (OLETF), an animal model of obesity and type 2 diabetes. Consistent with that higher vaspin serum concentrations and increased vaspin mRNA expression in human adipose tissue were found to be associated with obesity, insulin resistance, and type 2 diabetes in humans. However, the mechanisms how vaspin secretion may be linked to deterioration of glucose metabolism and insulin sensitivity are not entirely understood. Vaspin serum concentrations show a food intake-related diurnal variation. Vaspin is also expressed in the skin, hypothalamus, pancreatic islets, and stomach. Administration of vaspin to obese mice improves glucose tolerance, insulin sensitivity, and reduces food intake. Until now molecular target(s) of vaspin and its mode of action are unknown. Thus, identification of the proteases, which are inhibited by vaspin may lead to the development of novel strategies in the treatment of obesity, diabetes and insulin resistance. This review discusses the clinical relevance of vaspin in the pathophysiology of obesity and type 2 diabetes. © 2012 Springer Science+Business Media, LLC.


Mayr S.G.,Leibniz Institute fur Oberflachenmodifizierung E.V. | Mayr S.G.,University of Leipzig | Arabi-Hashemi A.,Leibniz Institute fur Oberflachenmodifizierung E.V.
New Journal of Physics | Year: 2012

Fe-Pd-based ferromagnetic shape memory alloys constitute an exciting class of magnetically switchable smart materials that reveal excellent mechanical properties and biocompatibility. However, their application is severely hampered by a lack of understanding of the physics at the atomic scale. A many-body potential is presented that matched ab inito calculations and can account for the energetics of martensite ↔ austenite transition along the Bain path and relative phase stabilities in the ordered and disordered phases of Fe-Pd. Employed in massively parallel classical molecular dynamics simulations, the impact of order/disorder, point defects and severe plastic deformation in the presence of single- and polycrystalline microstructures are explored as a function of temperature. The model predictions are in agreement with experiments on phase changes induced by ion irradiation, cold rolling and hammering, which are also presented. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.


Nam C.C.W.,Max Planck Institute for Meteorology | Nam C.C.W.,Laboratoire Of Meteorologie Dynamique | Quaas J.,Max Planck Institute for Meteorology | Quaas J.,University of Leipzig
Journal of Climate | Year: 2012

Observations from Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) and CloudSat satellites are used to evaluate clouds and precipitation in the ECHAM5 general circulation model. Active lidar and radar instruments on board CALIPSO and CloudSat allow the vertical distribution of clouds and their optical properties to be studied on a global scale. To evaluate the clouds modeled by ECHAM5with CALIPSO and CloudSat, the lidar and radar satellite simulators of the Cloud Feedback Model Intercomparison Project's Observation Simulator Package are used. Comparison of ECHAM5 with CALIPSO and CloudSat found large-scale features resolved by the model, such as the Hadley circulation, are captured well. The lidar simulator demonstrated ECHAM5 overestimates the amount of high-level clouds, particularly optically thin clouds. High-altitude clouds in ECHAM5 consistently produced greater lidar scattering ratios compared with CALIPSO. Consequently, the lidar signal in ECHAM5 frequently attenuated high in the atmosphere. The large scattering ratios were due to an underestimation of effective ice crystal radii in ECHAM5. Doubling the effective ice crystal radii improved the scattering ratios and frequency of attenuation. Additionally, doubling the effective ice crystal radii improved the detection of ECHAM5's highest-level clouds by the radar simulator, in better agreement with CloudSat. ECHAM5 was also shown to significantly underestimate midlevel clouds and (sub)tropical low-level clouds. The low-level clouds produced were consistently perceived by the lidar simulator as too optically thick. The radar simulator demonstrated ECHAM5 overestimates the frequency of precipitation, yet underestimates its intensity compared with CloudSat observations. These findings imply compensating mechanisms inECHAM5 balance out the radiative imbalance caused by incorrect optical properties of clouds and consistently large hydrometeors in the atmosphere. © 2012 American Meteorological Society.


Lechner G.,University of Leipzig | Longo R.,University of Rome Tor Vergata
Communications in Mathematical Physics | Year: 2015

Starting from a real standard subspace of a Hilbert space and a representation of the translation group with natural properties, we construct and analyze for each endomorphism of this pair a local, translationally covariant net of standard subspaces, on the lightray and on two-dimensional Minkowski space. These nets share many features with low-dimensional quantum field theory, described by corresponding nets of von Neumann algebras.Generalizing a result of Longo and Witten to two dimensions and massive multiplicity free representations, we characterize these endomorphisms in terms of specific analytic functions. Such a characterization then allows us to analyze the corresponding nets of standard spaces, and in particular to compute their minimal localization length. The analogies and differences to the von Neumann algebraic situation are discussed. © 2014, Springer-Verlag Berlin Heidelberg.


Stadler S.C.,University of Leipzig | Allis C.D.,Rockefeller University
Seminars in Cancer Biology | Year: 2012

Cancer, as well as other human disorders, has long been considered to result from the consequence of genetic mutations in key regulatory genes that reside in pathways controlling proliferation, cellular differentiation, DNA damage and repair. In the case of cancer, mutations are well documented to arise in key oncogenes and critically important tumor-suppressor genes as part of the disease progression process. In addition to more accepted, genetic mutations, a rapidly increasing body of evidence supports the general view that profound alterations also occur in 'epigenes', whose products serve to define the 'epigenetic landscape' of tumor cells. Aberrant changes in epigenetic mechanisms such as DNA methylation, histone modifications and expression of micro RNAs play an important role in cancer and contribute to malignant transitions. Here we review recent studies linking epigenetic mechanisms to epithelial-to-mesenchymal transition as defined in normal processes, as well as abnormal transitions that lead to oncogensis. © 2012 Elsevier Ltd.


Bluher M.,University of Leipzig
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2012

Purpose of review: Obesity is associated with an increased risk of premature death and represents a fast growing worldwide health problem that is reaching epidemic proportions. Obesity significantly increases the risk of developing metabolic disorders, hypertension, coronary heart disease, stroke, and several types of cancer. However, a subgroup of 'healthy' obese patients seems to be protected against metabolic and cardiovascular obesity comorbidities. This review focuses on potential mechanisms underlying the healthy obese subphenotype. Recent findings: Individuals with obesity typically develop type 2 diabetes, dyslipidemia, fatty liver disease, gout, hypertension, and cardiovascular disease. In the past years it became clear that up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy lean individuals, lower liver fat content, and lower intima media thickness of the carotid artery than the majority of metabolically 'unhealthy' obese patients. Recent studies suggest that protection against development of hepatic steatosis, ectopic fat deposition, inflammation of visceral adipose tissue, and adipose tissue dysfunction contributes to healthy obesity. Summary: For the stratification of obesity treatment, definition of metabolically healthy or high-risk phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, bariatric surgery, or pharmacological interventions. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Gebhardt J.,University of Leipzig | Schulz-Juergensen S.,University of Kiel | Eggert P.,University of Kiel
Psychophysiology | Year: 2012

It is known that sensorimotor gating measured by the prepulse inhibition of the startle reflex (PPI) matures during childhood. Since certain disorders in children, for example, enuresis, show a significant loss in PPI, the PPI as a tool for investigating brainstem reflex control mechanism gains in importance. Therefore, it is crucial to know the natural course of PPI maturation in childhood. A total of 122 healthy children aged from 3-10 years and 10 healthy adults were examined. PPI was initiated by a 120ms and a 60ms prepulse and was measured by the EMG of M. orbicularis oculi. For the respective prepulse intervals, the PPI level in each age group increased from 3 to 9 or 10 years and showed a similar course. The findings confirm and extend knowledge about the maturation of PPI during childhood and emphasize the importance of age-dependent standard values when investigating PPI in children. © 2011 Society for Psychophysiological Research.


Stevenson P.A.,University of Leipzig | Rillich J.,Free University of Berlin
PLoS ONE | Year: 2013

Population density has profound influences on the physiology and behaviour of many animal species. Social isolation is generally reported to lead to increased aggressiveness, while grouping lowers it. We evaluated the effects of varying degrees of isolation and grouping on aggression in a territorial insect, the Mediterranean field cricket, Gryllus bimaculatus. Substantiating early observations, we show that dyadic contests between weight-matched, adult male crickets taken from groups rarely escalate beyond threat displays, whereas interactions between pairs of previously isolated crickets typically escalate to physical fights lasting several seconds. No significant differences were found between 1, 2 and 6-day isolates, or between individuals grouped for a few hours or lifelong. Unexpectedly, crickets grouped in immediate proximity within individual mesh cages that precluded fighting while permitting visual, olfactory and mechanical, antennal contact, were as aggressive as free isolates. This suggests that reduced aggression of grouped animals may be an acquired result of fighting. Supporting this notion, isolated crickets initially engage in vigorous fights when first grouped, but fighting intensity and duration rapidly decline to the level of life-long grouped crickets within only 10 min. Furthermore, grouped crickets become as aggressive as life-long isolates after only 3 hours of isolation, and on the same time course required for crickets to regain their aggressiveness after social defeat. We conclude that the reduced aggressiveness of grouped crickets is a manifestation of the loser effect resulting from social subjugation, while isolation allows recovery to a state of heightened aggressiveness, which in crickets can be considered as the default condition. Given the widespread occurrence of the loser effect in the Animal Kingdom, many effects generally attributed to social isolation are likely to be a consequence of recovery from social subjugation. © 2013 Stevenson et al.


Pazaitou-Panayiotou K.,Theagenion Cancer Hospital | Michalakis K.,Queen Mary, University of London | Paschke R.,University of Leipzig
Hormone and Metabolic Research | Year: 2012

Thyroid cancer can be associated with thyrotoxicosis caused by Graves' disease, toxic multinodular goiter, or autonomously functioning thyroid adenoma. The objective of this study was to summarize current evidence regarding the association of thyroid cancer and hyperthyroidism, particularly with respect to the type of hyperthyroidism found in some patients, and whether this affects the outcome of the patient. A PubMed search was performed up to August 2011. Articles were identified using combinations of the following keywords/phrases: thyroid cancer, papillary thyroid cancer, follicular thyroid cancer, medullary thyroid cancer, anaplastic thyroid cancer, hyperthyroidism, Graves' disease, autonomous adenoma, toxic thyroid nodule, and toxic multinodular goiter. Original research papers, case reports, and review articles were included. We concluded that the incidence, as well as the prognosis of thyroid cancer associated with hyperthyroidism is a matter of debate. It seems that Graves' disease is associated with larger, multifocal, and potentially more aggressive thyroid cancer than single hot nodules or multinodular toxic goiter. Patients with Graves' and thyroid nodules are at higher risk to develop thyroid cancer compared to patients with diffuse goiter. Every suspicious nodule associated with hyperthyroidism should be evaluated carefully. © Georg Thieme Verlag KG Stuttgart · New York.


Gomez-Ruiz S.,Rey Juan Carlos University | Hey-Hawkins E.,University of Leipzig
Coordination Chemistry Reviews | Year: 2011

In this review, the synthesis, reactivity and properties of linear and cyclic oligophosphanides are described. Specifically the structures and versatile reactivity of the anionic ligands (P4R4)2- (R=But, Ph, Mes), (P4HR4)- (R=Ph and Mes) and cyclo-(P5But4)- towards main group and transition metal complexes is elucidated. In addition, potential application of metal oligophosphanides as precursors for the preparation of metal phosphides is also briefly discussed. © 2010 Elsevier B.V.


Whitington P.M.,University of Melbourne | Mayer G.,University of Leipzig
Arthropod Structure and Development | Year: 2011

A revision of evolutionary relationships of the Arthropoda has provided fresh impetus to tracing the origins of the nervous system of this group of animals: other members of the Ecdysozoa possess a markedly different type of nervous system from both the arthropods and the annelid worms, with which they were previously grouped. Given their status as favoured sister taxon of the arthropods, Onychophora (velvet worms) are a key group for understanding the evolutionary changes that have taken place in the panarthropod (Arthropoda + Onychophora + Tardigrada) lineage. This article reviews our current knowledge of the structure and development of the onychophoran nervous system. The picture that emerges from these studies is that the nervous system of the panarthropod ancestor was substantially different from that of modern arthropods: this animal probably possessed a bipartite, rather than a tripartite brain; its nerve cord displayed only a limited degree of segmentation; and neurons were more numerous but more uniform in morphology than in living arthropods. These observations suggest an evolutionary scenario, by which the arthropod nervous system evolved from a system of orthogonally crossing nerve tracts present in both a presumed protostome ancestor and many extant worm-like invertebrates, including the onychophorans. © 2011.


Siefermann K.R.,University of Gottingen | Abel B.,University of Leipzig
Angewandte Chemie - International Edition | Year: 2011

Since the discovery of the hydrated electron in bulk water in 1962, the species has been the subject of intense research and speculation. For many decades even the basic features of the simplest of all chemical and biological transients and reactants-such as its structure, binding motifs, lifetimes, and binding energies-remained elusive. Recently, another milestone in the research of the hydrated electron was the determination of its vertical binding energy (VBE). Also a long-lived hydrated electron near the surface of liquid water has been discovered. The present Minireview discusses the implications and consequences of this and other new findings in addition to the emerging complex picture of a solvated electron in water. Two recent milestones in the research of the hydrated electron were the determination of its vertical binding energy and the discovery of a long-lived hydrated electron near the surface of liquid water. The results bear relevance for many fields, e.g., electron attachment to DNA bases (see picture). © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Fichtner I.,University of Leipzig
Theory of Computing Systems | Year: 2011

We investigate formal power series on pictures. These are functions that map pictures to elements of a semiring and provide an extension of two-dimensional languages to a quantitative setting. We establish a notion of a weighted MSO logics over pictures. The semantics of a weighted formula will be a picture series. We introduce weighted 2-dimensional on-line tessellation automata (W2OTA) and prove that for commutative semirings, the class of picture series defined by sentences of the weighted logics coincides with the family of picture series that are computable by W2OTA. Moreover, we show that the family of behaviors of W2OTA coincide precisely with the class of picture series characterized by weighted (quadrapolic) picture automata and consequently, the notion of weighted recognizability presented here is robust. However, the weighted structures can not be used to get better decidability properties than in the language case. For every commutative semiring, it is undecidable whether a given MSO formula has restricted structure or whether the semantics of a formula has empty support. © 2009 Springer Science+Business Media, LLC.


Lohrey M.,University of Leipzig
Information and Computation | Year: 2011

Tight connections between leaf languages and strings compressed by straight-line programs (SLPs) are established. It is shown that the compressed membership problem for a language L is complete for the leaf language class defined by L via logspace machines. A more difficult variant of the compressed membership problem for L is shown to be complete for the leaf language class defined by L via polynomial time machines. As a corollary, it is shown that there exists a fixed linear visibly pushdown language for which the compressed membership problem is PSPACE-complete. For XML languages, it is shown that the compressed membership problem is coNP-complete.Furthermore it is shown that the embedding problem for SLP-compressed strings is hard for PP (probabilistic polynomial time). © 2011 Elsevier Inc. All rights reserved.


Karger J.,University of Leipzig
ChemPhysChem | Year: 2015

Diffusion, that is, the irregular movement of atoms and molecules, is a universal phenomenon of mass transfer occurring in all states of matter. It is of equal importance for fundamental research and technological applications. The present review deals with the challenges of the reliable observation of these phenomena in nanoporous materials. Starting with a survey of the different variants of diffusion measurement, it highlights the potentials of "microscopic" techniques, notably the pulsed field gradient (PFG) technique of NMR and the techniques of microimaging by interference microscopy (IFM) and IR microscopy (IRM). Considering ensembles of guest molecules, these techniques are able to directly record mass transfer phenomena over distances of typically micrometers. Their concerted application has given rise to the clarification of long-standing discrepancies, notably between microscopic equilibrium and macroscopic non-equilibrium measurements, and to a wealth of new information about molecular transport under confinement, hitherto often inaccessible and sometimes even unimaginable. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.


Remus R.,University of Leipzig
Proceedings - 12th IEEE International Conference on Data Mining Workshops, ICDMW 2012 | Year: 2012

We propose an approach to domain adaptation that selects instances from a source domain training set, which are most similar to a target domain. The factor by which the original source domain training set size is reduced is determined automatically by measuring domain similarity between source and target domain as well as their domain complexity variance. Domain similarity is measured as divergence between term unigram distributions. Domain complexity is measured as homogeneity, i.e. self-similarity. We evaluate our approach in a semi-supervised cross-domain document-level polarity classification experiment. Thereby we show, that it yields small but statistically significant improvements over several natural baselines and achieves results competitive to other state-of-the-art domain adaptation schemes. © 2012 IEEE.


Gottken T.,University of Leipzig
Praxis der Kinderpsychologie und Kinderpsychiatrie | Year: 2013

This review gives an overview on recent psychodynamic concepts of depression and contrasts them with recent bio-psycho-social and genetic approaches on the aetiopathogenesis of depression. The implication of current findings from these disciplines is discussed in the context of interventional strategies and clinical praxis. © Vandenhoeck & Ruprecht GmbH & Co. KG, Göttingen 2013.


Wittekind C.,University of Leipzig
Pathology International | Year: 2015

The first tumor, node, metastasis (TNM) classification for stomach tumors was published in the second edition of the TNM classification of malignant tumors in 1974 and was followed by additional editions up to the seventh edition published in 2010. In the Buffalo Meeting 2008 a harmonization between the Eastern (Japanese) and Western stomach tumor classification was achieved with only minor remaing differences. The present TNM classification of stomach tumors has been criticized but it can be considered generally accepted worldwide. For generating data based on this new TNM classification it is important to correctly use TNM and pTNM. The decions on therapy and the estimation of prognosis are based on TNM. New molecular factor studies will be correlated and based on the results of the TNM classification. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.


Mierke C.T.,University of Leipzig
Journal of Biological Chemistry | Year: 2011

Metastasis is a key event of malignant tumor progression. The capability to metastasize depends on the ability of the cancer cell to migrate into connective tissue, adhere, and possibly transmigrate through the endothelium. Previously we reported that the endothelium does not generally act as barrier for cancer cells to migrate in three-dimensional extracellular matrices (3D-ECMs). Instead, the endothelium acts as an enhancer or a promoter for the invasiveness of certain cancer cells. How invasive cancer cells diminish the endothelial barrier function still remains elusive. Therefore, this study investigates whether invasive cancer cells can decrease the endothelial barrier function through alterations of endothelial biomechanical properties. To address this, MDA-MB-231 breast cancer cells were used that invade deeper and more numerous into 3D-ECMs when co-cultured with microvascular endothelial cells. Using magnetic tweezer measurements, MDA-MB-231 cells were found to alter the mechanical properties of endothelial cells by reducing endothelial cell stiffness. Using spontaneous bead diffusion, actin cytoskeletal remodeling dynamics were shown to be increased in endothelial cells co-cultured with MDA-MB-231 cells compared with mono-cultured endothelial cells. In addition, knockdown of the α5 integrin subunit in highly transmigrating α5β1 high cells derived from breast, bladder, and kidney cancer cells abolished the endothelial invasion-enhancing effect comparable with the inhibition of myosin light chain kinase. These results indicate that the endothelial invasion-enhancing effect is α5β1 integrin-dependent. Moreover, inhibition of Rac-1, Rho kinase,MEKkinase, and PI3K reduced the endothelial invasion-enhancing effect, indicating that signaling via small GTPases may play a role in the endothelial facilitated increased invasiveness of cancer cells. In conclusion, decreased stiffness and increased cytoskeletal remodeling dynamics of endothelial cells may account for the breakdown of endothelial barrier function, suggesting that biomechanical alterations are sufficient to facilitate the transmigration and invasion of invasive cancer cells into 3D-ECMs. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.


Seliger B.,Martin Luther University of Halle Wittenberg | Quandt D.,Martin Luther University of Halle Wittenberg | Quandt D.,University of Leipzig
Cancer Immunology, Immunotherapy | Year: 2012

The modulation and suppression of anti-Tumor immune responses is a characteristic feature of tumor cells to escape immune surveillance. Members of the B7 family are involved in this process, since the level of activation of the anti-Tumor immune response depends on the balance between co-stimulatory and co-inhibitory signals. Some molecules are often overexpressed in tumors, which has been associated with the pathogenesis and progression of malignancies as well as their immunological and nonimmunological functions. The B7 homologs play a key role in the maintenance of self-Tolerance and the regulation of both innate and adaptive immunity in tumor-bearing hosts. Furthermore, the blockade of negative signals mediated by the interaction of co-inhibitory ligands and counter-receptors of the B7 family is currently being studied as a potential immunotherapeutic strategy for the treatment of cancer in humans. © Springer-Verlag 2012.


Bluher M.,University of Leipzig
Clinical Lipidology | Year: 2010

The incidence of obesity has increased dramatically during recent decades. Obesity will cause a decline in life expectancy for the first time in recent history owing to numerous comorbid disorders, including increased risk of insulin resistance, Type 2 diabetes, fatty liver disease, hypertension, dyslipidemia, atherosclerosis, dementia, airway disease and some cancers. However, the mechanisms linking increased adipose mass in obesity to these disorders are not fully understood. Adipose tissue is an active endocrine organ that releases a large number of cytokines and bioactive mediators, termed adipokines. Identification of novel adipokines, which may link obesity to its related diseases, represents a hot topic in obesity research. © 2010 Future Medicine Ltd.


Stark A.,University of Leipzig
Journal of Molecular Liquids | Year: 2014

It is well known that the physical and chemical properties of ionic liquids are dependent on their structure. Understanding the types and strengths of interactions is necessary for a knowledge-based design of ionic liquid structures. In the first section, we introduce some of our recent physico-chemical and spectroscopic investigations on binary ionic liquid+solute mixtures (with water, an organic solute or a second ionic liquid), showing that hydrogen bonding plays a vital role for the arrangement of the ions in mixtures, and preferential interactions can lead to subtle changes resulting in deviation from ideal mixing behavior. The second section shows examples of how specific interactions with solutes affect reactions and other processes, regarding e.g. the rate of reaction, yields, extraction efficiencies, dissolution capacities of biofeeds, and selectivity in crystal framework formation. The third section is dedicated to some examples regarding the development of ionic liquids as materials. © 2013 Elsevier B.V. All rights reserved.


Belener K.L.A.,Saarland University | Kohlmann H.,University of Leipzig
Journal of Magnetism and Magnetic Materials | Year: 2014

A modified oxide-reduction-diffusion (ORD) method for the synthesis of single-phase SmCo5 is described. Samarium oxide, cobalt and calcium (20% excess) are heated in sealed niobium tubes following an optimized temperature programme. The reaction proceeds via Ca1-xSmxO as an intermediate and yields SmCo5, and CaO, which may be washed off with dilute acetic acid. Single-phase SmCo5 prepared by this route shows an enhanced reactivity towards hydrogen and reacts already at moderate conditions of p(H2)=0.1 MPa and T<770 K. in situ difference scanning calorimetry and X-ray powder diffraction suggest the formation of ternary hydrides SmCo5Hx at temperatures around 473 and 573 K, and disproportionation into cobalt of poor crystallinity and probably an amorphous binary samarium hydride at 700 K, i.e. a hydrogen induced amorphization (HIA) of SmCo5. Neutron powder diffraction was carried out on a 154SmCo5 sample with the high-intensity neutron powder diffractometer D20 at the Institute Laue-Langevin, Grenoble, France. The CaCu5 type crystal structure was confirmed (space group P6/mmm, a=500.60 (2) pm, c=397.01 (2) pm at T=298 (1) K) and the magnetic moments along the crystallographic c axis, μ||c, were refined to be 0.15 (6), 2.02 (6) and 1.75 (5) μB for Sm, Co1 and Co2 atoms, respectively, in ferromagnetic SmCo5. The HIA process was confirmed by in situ neutron powder diffraction at higher pressures of 8.1 MPa deuterium gas. © 2014 Elsevier B.V.


Sens-Schonfelder C.,German Research Center for Geosciences | Pomponi E.,University of Leipzig | Peltier A.,CNRS Paris Institute of Global Physics
Journal of Volcanology and Geothermal Research | Year: 2014

Activity of Piton de la Fournaise (PdF) volcano in La Réunion Island modifies the seismic velocities within the edifice. Using the 2010 and 2011 data from a network of 21 seismic stations in the vicinity of PdF, changes of seismic velocities are investigated using passive image interferometry, i.e. interferometry of seismic noise correlations. As noise correlations change significantly over time in response to volcanic activity, a method is presented that allows us to measure continuous long term velocity changes with high and constant accuracy by using multiple periods as reference. A long term velocity increase is found that averages about 0.25% per year. This trend is superimposed by short term changes that exhibit a clear connection with summit seismo-tectonic earthquakes indicating the effect of volcanic activity. Characteristic signatures of velocity changes are identified for post-eruptive periods of deflation that show an increase of velocity associated with subsidence observed by GPS. Periods of pre-eruptive inflation are characterized by decreasing velocity. Seismic crises can be associated with either increasing or decreasing velocity depending on whether the magma movement leads to deflation due to an eruption emptying the shallow plumbing system or to inflation caused by a non-eruptive intrusion. With a simple assumption about the spatial sensitivity of the measurements both processes are found to have the strongest effect in the central summit area of the volcano which also shows the strongest surface displacements during the time investigated here. We do not observe a dependence of the velocity change on the location of the erupting fissures, instead the distribution of changes for the three inflation periods and the two eruptions are similar indicating that the velocity changes observed here reflect the dynamics of a shallow magma reservoir rather than the effect of the eruption at the surface. © 2014.


Treudler R.,University of Leipzig
JDDG - Journal of the German Society of Dermatology | Year: 2012

Summary Component-resolved diagnostics (CRD) have become of growing importance in clinical investigation of IgE-mediated allergies. This review updates the current use of CRD in respiratory allergies (e. g. to pollen, animal dander, mites, latex), as well as in allergies to hymenoptera venom or in food allergies to plants (e. g. Bet v 1 homologues, lipid transfer proteins, storage proteins) or to animal-derived food allergens (e. g. milk, meat, fish). CRD may help to elucidate the clinical relevance of an allergic sensitization. In some cases, CRD may also be useful in predicting either severity of clinical reactions or the therapeutic effect of specific immunotherapy. © 2012 Blackwell Verlag GmbH, Berlin.


Horvath J.,Hungarian Academy of Sciences | Bendixen A.,University of Leipzig
International Journal of Psychophysiology | Year: 2012

Involuntary attention switches triggered by infrequent, unpredictably occurring sensory events (distraction) can be prevented when participants are made aware of the forthcoming distractor. Previous studies exploring this phenomenon presented visual cues before each stimulus in an auditory oddball sequence. In one condition, cues were completely reliable in predicting the forthcoming distractor or standard sound, in another, separate condition, they were completely unreliable. These studies found that in the condition with reliable cues, distraction was reduced compared to that with unreliable cues, as signaled by decreased reaction time delay as well as reduced P3a and reorienting negativity event-related potentials. Whereas these results are generally interpreted as the results of preparatory processes initiated by the cues, it could be argued that the preventive effect is a byproduct of increased information processing load in the condition with informative cues compared to that in the condition with uninformative ones. In the present study, using 80% reliable visual cues preceding tones in an oddball sequence, it was demonstrated that distraction can be prevented when the trials with valid and invalid cues were presented within a single experimental condition, as shown by reduced reaction time delay and P3a amplitude. These results are compatible with the notion that the distraction is prevented by means of preparatory processes initiated by the cues. © 2011 Elsevier B.V..


Wit J.M.,Leiden University | Kiess W.,University of Leipzig | Mullis P.,University of Bern
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

After a proper medical history, growth analysis and physical examination of a short child, followed by radiological and laboratory screening, the clinician may decide to perform genetic testing. We propose several clinical algorithms that can be used to establish the diagnosis. GH1 and GHRHR should be tested in children with severe isolated growth hormone deficiency and a positive family history. A multiple pituitary dysfunction can be caused by defects in several genes, of which PROP1 and POU1F1 are most common. GH resistance can be caused by genetic defects in GHR, STAT5B, IGF1, IGFALS, which all have their specific clinical and biochemical characteristics. IGF-I resistance is seen in heterozygous defects of the IGF1R. If besides short stature additional abnormalities are present, these should be matched with known dysmorphic syndromes. If no obvious candidate gene can be determined, a whole genome approach can be taken to check for deletions, duplications and/or uniparental disomies. © 2010 Elsevier Ltd. All rights reserved.


Weise C.M.,University of Leipzig | Hohenadel M.G.,U.S. National Institutes of Health | Krakoff J.,U.S. National Institutes of Health | Votruba S.B.,U.S. National Institutes of Health
International Journal of Obesity | Year: 2014

Background:Obesity is the result of chronic positive energy balance. The mechanisms underlying the regulation of energy homeostasis and food intake are not understood. Despite large increases in fat mass (FM), recent evidence indicates that fat-free mass (FFM) rather than FM is positively associated with intake in humans.Methods:In 184 humans (73 females/111 males; age 34.5±8.8 years; percentage body fat: 31.6±8.1%), we investigated the relationship of FFM index (FFMI, kg m -2), FM index (FMI, kg m -2); and 24-h energy expenditure (EE, n=127) with ad-libitum food intake using a 3-day vending machine paradigm. Mean daily calories (CAL) and macronutrient intake (PRO, CHO, FAT) were determined and used to calculate the relative caloric contribution of each (%PRO, %CHO, %FAT) and percent of caloric intake over weight maintaining energy needs (%WMENs).Results:FFMI was positively associated with CAL (P<0.0001), PRO (P=0.0001), CHO (P=0.0075) and FAT (P<0.0001). This remained significant after adjusting for FMI. Total EE predicted CAL and macronutrient intake (all P<0.0001). FMI was positively associated with CAL (P=0.019), PRO (P=0.025) and FAT (P=0.0008). In models with both FFMI and FMI, FMI was negatively associated with CAL (P=0.019) and PRO (P=0.033). Both FFMI and FMI were negatively associated with %CHO and positively associated with %FAT (all P<0.001). EE and FFMI (adjusted for FMI) were positively (EE P=0.0085; FFMI P=0.0018) and FMI negatively (P=0.0018; adjusted for FFMI) associated with %WMEN.Conclusion:Food and macronutrient intake are predicted by FFMI and to a lesser degree by FMI. FFM and FM may have opposing effects on energy homeostasis. © 2014 Macmillan Publishers Limited.


Bellouin N.,UK Met Office | Bellouin N.,University of Reading | Quaas J.,University of Leipzig | Morcrette J.-J.,European Center for Medium Range Weather Forecast | Boucher O.,University Pierre and Marie Curie
Atmospheric Chemistry and Physics | Year: 2013

The European Centre for Medium-range Weather Forecast (ECMWF) provides an aerosol re-analysis starting from year 2003 for the Monitoring Atmospheric Composition and Climate (MACC) project. The re-analysis assimilates total aerosol optical depth retrieved by the Moderate Resolution Imaging Spectroradiometer (MODIS) to correct for model departures from observed aerosols. The re-analysis therefore combines satellite retrievals with the full spatial coverage of a numerical model. Re-analysed products are used here to estimate the shortwave direct and first indirect radiative forcing of anthropogenic aerosols over the period 2003-2010, using methods previously applied to satellite retrievals of aerosols and clouds. The best estimate of globally-averaged, all-sky direct radiative forcing is-0.7 ± 0.3 Wm−2. The standard deviation is obtained by a Monte-Carlo analysis of uncertainties, which accounts for uncertainties in the aerosol anthropogenic fraction, aerosol absorption, and cloudy-sky effects. Further accounting for differences between the present-day natural and pre-industrial aerosols provides a direct radiative forcing estimate of-0.4 ± 0.3 Wm−2. The best estimate of globally-averaged, all-sky first indirect radiative forcing is-0.6 ± 0.4 Wm−2. Its standard deviation accounts for uncertainties in the aerosol anthropogenic fraction, and in cloud albedo and cloud droplet number concentration susceptibilities to aerosol changes. The distribution of first indirect radiative forcing is asymmetric and is bounded by-0.1 and-2.0 Wm-2. In order to decrease uncertainty ranges, better observational constraints on aerosol absorption and sensitivity of cloud droplet number concentrations to aerosol changes are required. © 2013 Author(s).


Spanel-Borowski K.,University of Leipzig
Advances in Anatomy Embryology and Cell Biology | Year: 2011

This monograph introduces innate immunity as a second force in the ovary in addition to the endocrine system. Innate immunity appears to orchestrate follicular atresia, follicle rupture, and follicle transformation into a corpus luteum (CL) and CL regression through sterile inflammation and tissue repair. The concept is new. It centers on cytokeratin-positive (CK+) cells being recognized as a potential non lymphoid dendritic cell (DC) type. Part I describes morphological aspects of immune privilege starting with hamster ovary implants into the chicken chorioallantoic membrane with a non reactive mesenchyme. Follicular atresia and follicle rupture correspond to mild and moderate tissue damage in ovaries of small rodents and rabbits. Superovulations cause severe tissue damage through intra-ovarian oocyte release with follicle wall remnants in oedema, rupture of vessel walls and thrombosis. The complement system and neuropeptides might play regulatory roles. Part IIa analyzes intact ovaries (cows, human) for the appearance of CK+ cells. In the fetal ovary, sex cords give rise to CK+ cells in primordial follicles. In the adult ovary, CK+ cells are absent in preantral follicles and reappear in mature and regressing follicles. In the CL of early development, steroidogenic CK+ cells build a peripheral zone in the previous granulosa cell layer, and are uniformly distributed in the following stages. A microvascular CK+ cell type is seldom found. Part IIb characterizes the morphology and function of CK+ cells in vitro. Isolated from human preovulatory follicles, the epithelioid CK+ granulosa cell subtype regulates TLR4 and CD14 at 36 h of treatment with oxidized lipoprotein (oxLDL, 150 μg/ml); non-apoptotic cell death and the increase of reactive oxygen species occur. In contrast, the CK-negative (CK1) granulosa cell type regulates the lectin-like oxLDL receptor 1 (LOX-1) and survival autophagy under oxLDL stimulation. Isolated from bovine CL, the epithelioid CK+ cell type 1 is disclosed as a microvascular cell type with a single nonmotile cilium. The microvascular CK+ type strongly upregulates intercellular contacts under treatment with interferon-γ (IFN-γ). In the CK- cell type 5 of granulosa cell-like appearance, IFN-γ treatment supports cell proliferation, Ncadherin upregulation, and the dramatic increase in major histocompatibility complex II peptides (MHC II) by 80-fold compared to basal levels. Type 5 could have been converted from the steroidogenic CK+ cell type. We summarize and conclude: CK+ granulosa cells express functionally active TLR4, which sense danger signals, such as oxidative stress in preovulatory follicles, and trigger inflammatory and immunoregulatory pathways. The final outcome regulates follicle rupture and transformation into CL. Luteolysis could start by dangersensing through the microvascular CK+ type 1 cells and the DC-like type 5 cells, both sensitive to IFN-γ. The future will witness a novel strategy in the therapy of ovarian disorders such as anovulations, luteal phase insufficiency and autoimmune failures. © Springer-Verlag Berlin Heidelberg 2011.


Genetic variations near the interferon lambda 3 gene (IFNL3, IL28B) are the most powerful predictors for sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection, compared to other biochemical or histological baseline parameters. We evaluated whether the interplay of both IFNL3 polymorphisms rs12979860 and rs8099917 together with non-genetic clinical factors contributes to the predictive role of these genetic variants. The cohort comprised 1,402 patients of European descent with chronic HCV type 1 infection. 1,298 patients received interferon-based antiviral therapy, and 719 (55%) achieved SVR. The IFNL3 polymorphisms were genotyped by polymerase chain reaction and melting curve analysis. A significant correlation was found between the IFNL3 polymorphisms and biochemical as well as virologic predictors of treatment outcome such as ALT, GGT, cholesterol, and HCV RNA levels. In multivariate regression analysis, IFLN3 SNPs, HCV RNA levels, and the GGT/ALT ratio were independent predictors of SVR. Dependent on the GGT/ALT ratio and on the HCV RNA concentration, significant variations in the likelihood for achieving SVR were observed in both, carriers of the responder as well as non-responder alleles. Our data support a clear association between IFNL3 genotypes and baseline parameters known to impact interferon responsiveness. Improved treatment outcome prediction was achieved when these predictors were considered in combination with the IFNL3 genotype.


Ngonga Ngomo A.-C.,University of Leipzig
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

Time-efficient algorithms are essential to address the complex linking tasks that arise when trying to discover links on the Web of Data. Although several lossless approaches have been developed for this exact purpose, they do not offer theoretical guarantees with respect to their performance. In this paper, we address this drawback by presenting the first Link Discovery approach with theoretical quality guarantees. In particular, we prove that given an achievable reduction ratio r, our Link Discovery approach can achieve a reduction ratio r′∈≤∈r in a metric space where distances are measured by the means of a Minkowski metric of any order p∈≥∈2. We compare and the HYPPO algorithm implemented in LIMES 0.5 with respect to the number of comparisons they carry out. In addition, we compare our approach with the algorithms implemented in the state-of-the-art frameworks LIMES 0.5 and SILK 2.5 with respect to runtime. We show that outperforms these previous approaches with respect to runtime in each of our four experimental setups. © 2012 Springer-Verlag Berlin Heidelberg.


Verch R.,University of Leipzig
Acta Physica Polonica B, Proceedings Supplement | Year: 2011

A sketch of an approach towards Lorentzian spectral geometry (based on joint work with Mario Paschke) is described, together with a general way to define abstractly the quantized Dirac field on such Lorentzian spectral geometries. Moyal-Minkowski spacetime serves as an example. The scattering of the quantized Dirac field by a non-commutative (Moyal-deformed) action of an external scalar potential is investigated. It is shown that differentiating the S-matrix with respect to the strength of the scattering potential gives rise to quantum field operators depending on elements of the non-commutative algebra entering the spectral geometry description of Moyal-Minkowski spacetime, in the spirit of "Bogoliubov's formula", in analogy to the situation found in external potential scattering by a usual scalar potential.


Sippel S.R.,University of Leipzig
Journal of Rural Studies | Year: 2016

While on a global scale the majority of farming is still organized around families, a sweeping observation across regional differences is that family farming takes on increasingly diversified forms. Within this context, hybrid concepts that bridge traditional notions have been suggested while research has also indicated an important interface between family farm businesses and multi-family farm structures. Drawing on this emerging body of literature, this paper develops the notion of 'multi-family farm entrepreneurs' to investigate the origin, background, and current organization of the families involved in agricultural export in Morocco. Based on extensive qualitative research, it is argued that the establishment of stable multi-family structures, which rely on active 'cohesive work', is key to understanding their success in the highly competitive and internationalized fruit and vegetable export sector. The paper demonstrates how family farm differentiation in the global South also takes place within the 'upper' level, with some family farmers developing entrepreneurial skills and becoming globally interconnected while contributing to a better understanding of the internal dynamics of this kind of farming. © 2016 Elsevier Ltd.


Paschke R.,University of Leipzig
Annales d'Endocrinologie | Year: 2011

Goitrogenisis is the consequence of a relative iodine deficiency interacting with a genetic predisposition for maladaptation to iodine deficiency. In the long run, the iodine deficiency induces increased H 2O 2 production that leads to an increased mutagenesis, resulting in somatic mutations with a proliferative advantage and thus the induction of thyroid nodules. © 2011 Elsevier Masson SAS.


Shahiduzzaman M.,Bangladesh Agricultural University | Daugschies A.,University of Leipzig
Veterinary Parasitology | Year: 2012

Cryptosporidiosis is a common gastro-intestinal illness in animals and man worldwide. The disease is devastating in immune-suppressed individuals but self-limiting in competent hosts. The infectious stages of the organism (oocysts) are shed in the faeces of affected individuals, survive in adverse environmental conditions and spread by direct contact or through contaminants (food, water). Due to the robustness of the oocysts, their tenacity, tiny size, and resistance to common disinfectants, the parasite is difficult to eradicate from contaminated environments. To obtain sufficient control both treatment of infected hosts and inactivation of oocysts are necessary. Several drugs are commonly used to treat cryptosporidiosis in man and very few in animals but none of them are completely effective in terms of both clinical and parasitological response. Only a few chemical agents are able to inactivate oocysts in the environment including water treatment plants but their application has certain limitations. Therefore, control of cryptosporidiosis remains a global challenge in both veterinary and human medicine. Extensive research has been performed on suitable drugs and disinfectants. Thousands of agents have been tested both in vivo and in vitro. Some are excitingly active in vitro but exhibit poor or no response in clinical trials. Currently, no single or combined drug therapy has proven to be completely effective against this disease. This article will focus on therapy and prevention of cryptosporidiosis in animals including perspectives for new drugs. © 2012 Elsevier B.V.


Seltmann K.,University of Leipzig
Journal of Investigative Dermatology | Year: 2015

Epidermal integrity and wound healing depend on remodeling of cell-matrix contacts including hemidesmosomes. Mutations in β4-integrin and plectin lead to severe epidermolysis bullosa (EB). Whether mutations in keratins K5 or K14, which cause EB simplex, also compromise cell-matrix adhesion through altering hemidesmosomal components is not well investigated. In particular, the dependence of β4-integrin endocytosis and turnover on keratins remains incompletely understood. Here, we show that the absence of keratins causes loss of plectin-β4-integrin interaction and elevated β4-integrin phosphorylation at Ser1354 and Ser1362. This triggered a caveolin-dependent endocytosis of β4-integrin but not of other integrins through Rab5 and Rab11 compartments in keratinocytes. Expressing a phospho–deficient β4-integrin mutant reduces β4-integrin endocytosis and rescues plectin localization in keratin–free cells. β4-integrin phosphorylation in the absence of keratins resulted from elevated Erk1/2 activity downstream of increased EGFR and PKCα signaling. Further, increased Erk1/2 phosphorylation and altered plectin localization occur in keratin–deficient mouse epidermis in vivo. Strikingly, expression of the K14-R125P EBS mutant also resulted in plectin mislocalization and elevated β4-integrin turnover, suggesting disease relevance. Our data underscore a major role of keratins in controlling β4-integrin endocytosis involving a plectin-Erk1/2-dependent mechanism relevant for epidermal differentiation and pathogenesis.Journal of Investigative Dermatology advance online publication, 12 March 2015; doi:10.1038/jid.2015.46. © 2015 The Society for Investigative Dermatology, Inc


Glaesmer H.,University of Leipzig
International psychogeriatrics / IPA | Year: 2011

Information on the prevalence and risk factors for depressive disorders in old age is of considerable interest for the assessment of future needs of the health care system. The aim of the study is to determine age- and gender-specific prevalence of major depression (MD), minor depression (MiD), and depressive symptoms, and to analyze risk factors associated with depressive symptoms. A representative sample of the German population of 1,659 individuals aged 60 to 85 years were visited at home and answered self-rating questionnaires. Depressive symptoms and syndromes (MD, MiD) were assessed using the Patient Health Questionnaire (PHQ-9). Factors associated with depressive symptoms were determined with linear regression models for the total sample and for men and women separately. Depressive symptoms were found in 28.7% of the participants, while 6.6% were affected by MD or MiD. The highest prevalence of MD and depressive symptoms was found in the oldest age groups. MiD showed an unsteady course across age groups in both sexes. In the total sample as well as in the male subsample, depressive symptoms were significantly associated with increasing age, lower household income, an increasing number of medical conditions, and lower social support. In women only, the number of medical conditions and lacking social support were significantly associated with depressive symptoms. Depressive symptoms are common in old age and occur on a spectrum ranging from very mild forms to MD. The potential modifiability of a number of risk factors for depressive symptoms opens possibilities of secondary prevention such as treatment of chronic diseases as well as support in requirements of daily living.


Quaas K.,University of Leipzig
Formal Methods in System Design | Year: 2011

We aim to generalize Büchi's fundamental theorem on the coincidence of recognizable and MSO-definable languages to a weighted timed setting. For this, we investigate weighted timed automata and show how we can extend Wilke's relative distance logic with weights taken from an arbitrary semiring. We show that every formula in our logic can effectively be transformed into a weighted timed automaton, and vice versa. The results indicate the robustness of weighted timed automata and may also be used for specification purposes. © Springer Science+Business Media, LLC 2011.


Jaeger M.,University of New South Wales | Jaeger M.,University of Leipzig | Lang E.W.,Red Cross
Neurocritical Care | Year: 2013

Background: To investigate the relationship between cerebrovascular pressure reactivity and cerebral oxygen regulation after head injury. Methods: Continuous monitoring of the partial pressure of brain tissue oxygen (P brO2), mean arterial blood pressure (MAP), and intracranial pressure (ICP) in 11 patients. The cerebrovascular pressure reactivity index (PRx) was calculated as the moving correlation coefficient between MAP and ICP. For assessment of the cerebral oxygen regulation system a brain tissue oxygen response (TOR) was calculated, where the response of P brO2 to an increase of the arterial oxygen through ventilation with 100 % oxygen for 15 min is tested. Arterial blood gas analysis was performed before and after changing ventilator settings. Results: Arterial oxygen increased from 108 ± 6 mmHg to 494 ± 68 mmHg during ventilation with 100 % oxygen. PbrO2 increased from 28 ± 7 mmHg to 78 ± 29 mmHg, resulting in a mean TOR of 0.48 ± 0.24. Mean PRx was 0.05 ± 0.22. The correlation between PRx and TOR was r = 0.69, P = 0.019. The correlation of PRx and TOR with the Glasgow outcome scale at 6 months was r = 0.47, P = 0.142; and r = -0.33, P = 0.32, respectively. Conclusions: The results suggest a strong link between cerebrovascular pressure reactivity and the brain's ability to control for its extracellular oxygen content. Their simultaneous impairment indicates that their common actuating element for cerebral blood flow control, the cerebral resistance vessels, are equally impaired in their ability to regulate for MAP fluctuations and changes in brain oxygen. © 2013 Springer Science+Business Media New York.


Eden B.,University of Leipzig | Korchemsky G.P.,CEA Saclay Nuclear Research Center | Sokatchev E.,University of Savoy
Journal of High Energy Physics | Year: 2011

We study the correlation functions of half-BPS protected operators in N = 4 super-Yang-Mills theory, in the limit where the positions of adjacent operators become light-like separated. We compute the loop corrections by means of Lagrangian insertions. The divergences resulting from the light-cone limit are regularized by changing the dimension of the integration measure over the insertion points. Switching from coordinates to dual momenta, we show that the logarithm of the correlation function is identical with twice the logarithm of the matching MHV gluon scattering amplitude. We present a number of examples of this new relation, at one and two loops.


Schmitto J.D.,Harvard University | Mohr F.W.,University of Leipzig | Cohn L.H.,Harvard University
Current Opinion in Cardiology | Year: 2011

Purpose of Review: Minimally invasive techniques are increasingly important in aortic valve surgery. The aim of this publication is to review our experience and recent literature to assess and present the current 'state-of-the-art'-role of minimally invasive aortic valve operations for high-risk patients. RECENT FINDINGS: Minimally invasive aortic valve operation for high-risk patients (e.g. patients with left ventricular dysfunction, reoperation, elderly, multimorbid patients, etc.) can be performed with an operative mortality similar to standard sternotomy approach. Less postoperative bleeding, fewer blood transfusions, better cosmesis, lower ICU and in-hospital stays as well as the absence of sternal wound infection are the main advantages of this technique. SUMMARY: Minimally invasive aortic valve surgery has evolved into a well tolerated, efficient surgical treatment option in experienced centers, providing greater patient satisfaction and lower complication rates in high-risk patients. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Grundmann M.,University of Leipzig
Physica Status Solidi (B) Basic Research | Year: 2010

The architecture of nano-and microdimensional building blocks has been investigated within the research group FOR 522 funded by the Deutsche Forschungsgemeinschaft. The main results are summarized in a series of papers following this article. Nanowires have been investigated for III-V-and II-VIsemiconductors and thermoelectric materials. Structures with curvature - screws, spirals, cylindrical tubes, and scrolls - have been achieved using substrate rotation during material deposition under glancing angle and employing strain, either between lattice planes in incommensurable structures or due to lattice mismatch in epitaxial heterostructures. The modification of physical properties due to conformal coverage with thin films, quantum wells, and dielectric Bragg mirrors has been investigated. Schematic geometry of various investigated structures: Nanowires (GaAs, InAs, GaN, ZnO, Bi2Te3), spirals (silicon), tubes (cylindrite, a sulfosalt, FePb3Sn4Sb2S14), and scrolls (InGaAs/BGaAs/GaAs), from left to right. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Ziese M.,University of Leipzig | Vrejoiu I.,Max Planck Institute of Microstructure Physics | Hesse D.,Max Planck Institute of Microstructure Physics
Physical Review B - Condensed Matter and Materials Physics | Year: 2010

The structural, magnetic, and magnetotransport properties of SrRuO 3 films grown on SrTiO3 (001) substrates were investigated with the aim to determine the crystalline symmetry, crystalline orientation, and magnetocrystalline anisotropy of an ultrathin (5 nm) SrRuO3 film. 60- and 40-nm-thick SrRuO3 films were extensively studied by transmission electron microscopy as well as magnetic and magnetotransport techniques, respectively. These studies showed orthorhombic symmetry with a slight monoclinic distortion and a well-defined long-range order of crystallographic domains with the [001] o axis parallel to terraces on the slightly vicinal SrTiO3 substrate. The magnetocrystalline anisotropy is very strong. The easy axis lies in the (001) o plane under a temperature-dependent angle of about 35° with respect to the [110] o direction that is along the film normal. Below 70 K indications for a spin reorientation transition were detected. The angular-dependent anisotropic magnetoresistance shows distinctive characteristics of the monoclinic symmetry that can be used as a fingerprint. Transmission electron microscopy images of the 5 nm thin SrRuO3 film show a coherently strained state. Using the fingerprints from the angular magnetoresistance it could be clearly shown that this ultrathin SrRuO3 film, although grown in step flow growth as well, has still monoclinic symmetry, but lacks long-range order of the crystallographic domains. A fraction of 30-40% of misaligned domains (rotated in plane by 90°) was estimated from the magnetoresistance curves. © 2010 The American Physical Society.


Zahn S.,University of Leipzig | Macfarlane D.R.,Monash University | Izgorodina E.I.,Monash University
Physical Chemistry Chemical Physics | Year: 2013

We present high-level benchmark calculations of interaction energies of 236 ion pair structures of ionic liquids constituting a new IL-2013 set. 33 different approaches using various basis sets are validated against these benchmark data. Overall, traditional functionals like B3LYP, without an explicit dispersion correction, should be avoided when investigating ionic liquids. We can recommend the third version of Grimme's empirical dispersion correction (DFT-D3) and the LC-BOP functional, as well as most functionals of the Minnesota family of the M0X type. Our results highlight the importance of diffuse basis set functions for the accurate prediction of the IL energetics using any DFT functional. The best combination of reasonable accuracy and reasonable cost was found to be the M06-L functional in combination with the 6-31++G** basis set, producing a remarkable mean absolute deviation of only 4.2 kJ mol-1 and a maximum deviation of -12.5 kJ mol-1. Second-order Møller-Plesset perturbation theory (MP2) in combination with counterpoise-corrected triple-ζ basis sets can also be recommended for reliable calculations of energetics of ionic liquids. © 2013 The Owner Societies.


Ziemer M.,University of Leipzig
JDDG - Journal of the German Society of Dermatology | Year: 2012

Atypical fibroxanthoma (AFX) is a rare neoplastic disease of the skin. Since the term was coined in the early 1960s, the disease has been viewed in many ways. For a long time AFX was regarded as a superficial variant of malignant fibrous histiocytoma (MFH). When the concept of MFH was re-evaluated and the term "undifferentiated pleomorphic sarcoma" (UPS) introduced, the controversy about the nature of AFX increased. The following review aims at providing an understanding of the present status of diagnosis and therapy of AFX based on the historical context and current data. © Blackwell Verlag GmbH, Berlin.


Karger J.,University of Leipzig
Microporous and Mesoporous Materials | Year: 2014

Experimental evidence leading to our present view on transport resistances on the external surface of nanoporous materials ("surface barriers") is reviewed. First substantial arguments for the existence of surface resistances was provided by the direct measurement of intracrystalline diffusion, enabled by the application of the pulsed field gradient (PFG) technique of NMR to sufficiently large zeolite crystallites. With the advent of the techniques of micro-imaging and the thus established avenue towards monitoring transient guest concentrations, first in-depth studies of surface barriers, based on the measurement of their permeabilities, have become possible. Highlights among these studies were the detection of surface barriers formed by impermeable layers with dispersed holes, giving rise to proportionality between surface permeation and intracrystalline diffusion, and the determination of "sticking factors" which, in the present context, refer to the probability that, after colliding with the external surface, a molecule of the gas phase will surmount the surface resistance and get into the genuine pore space. The formation of surface barriers is, in conclusion, shown to be a rather complex phenomenon whose in-depth exploration necessitates efforts comprising a large spectrum of activities over essentially all fields of zeolite research and technology. © 2013 Elsevier Ltd. All rights reserved.


Dagres N.,National and Kapodistrian University of Athens | Hindricks G.,University of Leipzig
European Heart Journal | Year: 2013

Patients who have experienced a myocardial infarction (MI) are at increased risk of sudden cardiac death (SCD). With the advent of implantable cardioverter-defibrillators (ICDs), accurate risk stratification has become very relevant. Numerous investigations have proven that a reduced left ventricular ejection fraction (LVEF) significantly increases the SCD risk. Furthermore, ICD implantation in patients with reduced LVEF confers significant survival benefit. As a result, LVEF is the cornerstone of current decision making for prophylactic ICD implantation after MI. However, LVEF as standalone risk stratifier has major limitations: (i) the majority of SCD cases occur in patients with preserved or moderately reduced LVEF, (ii) only relatively few patients with reduced LVEF will benefit from an ICD (most will never experience a threatening arrhythmic event, others have a high risk for non-sudden death), (iii) a reduced LVEF is a risk factor for both sudden and non-sudden death. Several other non-invasive and invasive risk stratifiers, such as ventricular ectopy, QRS duration, signal-averaged electrocardiogram, microvolt T-wave alternans, markers of autonomic tone as well as programmed ventricular stimulation, have been evaluated. However, none of these techniques has unequivocally demonstrated the efficacy when applied alone or in combination with LVEF. Apart from their limited sensitivity, most of them are risk factors for both sudden and non-sudden death. Considering the multiple mechanisms involved in SCD, it seems unlikely that a single test will prove adequate for all patients. A combination of clinical characteristics with selected stratification tools may significantly improve risk stratification in the future. © The Author 2013.


Sabin M.A.,Murdoch Childrens Research Institute | Werther G.A.,Murdoch Childrens Research Institute | Kiess W.,University of Leipzig
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

Childhood overweight and obesity is highly prevalent within society. In the majority of individuals, weight gain is the result of exposure to an 'obesogenic' environment, superimposed on a background of genetic susceptibility brought about by evolutionary adaptation. These individuals tend to be tall in childhood with a normal final adult height, as opposed to those who have an underlying monogenic cause where short stature is more common (although not universal). Identifying genetic causes of weight gain, or tall stature and overgrowth, within this setting can be extremely problematic and yet it is imperative that clinicians remain alert, as identification of a genetic diagnosis has major implications for the individual, family and potential offspring. Alongside this, the recognition of new genetic mutations in this area is furthering our knowledge on the important mechanisms that regulate childhood growth and body composition. This review describes the genetic syndromes associated with obesity and overgrowth. © 2010 Elsevier Ltd. All rights reserved.


Burchardt M.,University of Leipzig
Culture, Health and Sexuality | Year: 2011

Research on constructions of sexuality in Pentecostalism often struggles with the fact that the research setting is defined ex ante in terms of church communities, which imposes upon ethnographic accounts the same limitations Pentecostal morality imposes upon church members' discourse. Taking young Pentecostals operating in a space that is not explicitly religious as the methodological entrance to the field, this paper explores negotiations over sexuality, intimate relationships and love among Xhosa-speaking township youth. It introduces the notion of erotic geographies to consider how possible influences of religious discourses on sexuality are refracted by alternative cultural orientations and material contexts. Findings suggest that premarital abstinence appears as a highly exceptional ideal for youth. Even among Pentecostal youth, notions of sexuality are largely severed from religiosity and faithfulness and romanticism are dominant ideals. Future research on Pentecostalism and sexuality should be less religious-centric and rooted more firmly in ethnographies of youth sexual cultures. q 2011 Taylor & Francis.


Selmke M.,University of Leipzig
Journal of Quantitative Spectroscopy and Radiative Transfer | Year: 2015

The weak electromagnetic scattering of a special type of gradient index scatterer resembles the situation of charged particle scattering off an electrostatic Coulomb potential. Accordingly, plane-wave scattering for a radially symmetric decaying perturbation of the refractive index n(r)=n0-ν/k0r is studied. The experimental realization of this specific scattering is found in photothermal single particle microscopy. Vectorial scattering in Lorenz-Mie theory recovers the properties in the Born approximation of the corresponding potential scattering scenario. Shaped beams within the generalized Lorenz-Mie theory are found to resolve known pathologic properties of the problematic 1/. r potential. © 2015 Elsevier Ltd.


Integration of biomaterials into tissues is often disturbed by unopposed activation of macrophages. Immediately after implantation, monocytes are attracted from peripheral blood to the implantation site where they differentiate into macrophages. Inflammatory signals from the sterile tissue injury around the implanted biomaterial mediate the differentiation of monocytes into inflammatory M1 macrophages (M1) via autocrine and paracrine mechanisms. Suppression of sustained M1 differentiation is thought to be crucial to improve implant healing. Here, we explore whether artificial extracellular matrix (aECM) composed of collagen I and hyaluronan (HA) or sulfated HA-derivatives modulate this monocyte differentiation. We mimicked conditions of sterile tissue injury in vitro using a specific cytokine cocktail containing MCP-1, IL-6 and IFNγ, which induced in monocytes a phenotype similar to M1 macrophages (high expression of CD71, HLA-DR but no CD163 and release of high amounts of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12 and TNFα). In the presence of aECMs containing high sulfated HA this monocyte to M1 differentiation was disturbed. Specifically, pro-inflammatory functions were impaired as shown by reduced secretion of IL-1β, IL-8, IL-12 and TNFα. Instead, release of the immunregulatory cytokine IL-10 and expression of CD163, both markers specific for anti-inflammatory M2 macrophages (M2), were induced. We conclude that aECMs composed of collagen I and high sulfated HA possess immunomodulating capacities and skew monocyte to macrophage differentiation induced by pro-inflammatory signals of sterile injury toward M2 polarization suggesting them as an effective coating for biomaterials to improve their integration.


Gottwald S.,University of Leipzig
Fuzzy Sets and Systems | Year: 2010

The paper considers an early approach toward a (fuzzy) set theory with a graded membership predicate and a graded equality relation which had been developed by the German mathematician Klaua in 1965. In the context of the mathematical fuzzy logic MTL of left-continuous t-norms we discuss some properties of these graded relations. We compare the simultaneous recursive definitions of these relations with the very similar approach toward Boolean algebra valued interpretations of membership and equality, presented in 1967 by Scott and R. Solovay in the context of independence proofs for ZF set theory. Finally we speculate about possible reasons why Klaua soon abandoned this approach. © 2010 Elsevier B.V. All rightsreserved.


Mathissen C.,University of Leipzig
Logical Methods in Computer Science | Year: 2010

Nested words, a model for recursive programs proposed by Alur and Madhusudan, have recently gained much interest. In this paper we introduce quantitative extensions and study nested word series which assign to nested words elements of a semiring. We show that regular nested word series coincide with series definable in weighted logics as introduced by Droste and Gastin. For this we establish a connection between nested words and the free bisemigroup. Applying our result, we obtain characterizations of algebraic formal power series in terms of weighted logics. This generalizes results of Lautemann, Schwentick and Th ́erien on context-free languages. © C. Mathissen.


Poordad F.,University of Texas Health Science Center at San Antonio | Hezode C.,University Paris Est Creteil | Trinh R.,AbbVie | Kowdley K.V.,Virginia Mason Medical Center | And 13 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: Interferon-containing regimens for the treatment of hepatitis C virus (HCV) infection are associated with increased toxic effects in patients who also have cirrhosis. We evaluated the interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r), the NS5A inhibitor ombitasvir (ABT-267), the nonnucleoside polymerase inhibitor dasabuvir (ABT-333), and ribavirin in an open-label phase 3 trial involving previously untreated and previously treated adults with HCV genotype 1 infection and compensated cirrhosis. METHODS: We randomly assigned 380 patients with Child-Pugh class A cirrhosis to receive either 12 or 24 weeks of treatment with ABT-450/r-ombitasvir (at a once-daily dose of 150 mg of ABT-450, 100 mg of ritonavir, and 25 mg of ombitasvir), dasabuvir (250 mg twice daily), and ribavirin administered according to body weight. The primary efficacy end point was a sustained virologic response 12 weeks after the end of treatment. The rate of sustained virologic response in each group was compared with the estimated rate with a telaprevir-based regimen (47%; 95% confidence interval [CI], 41 to 54). A noninferiority margin of 10.5 percentage points established 43% as the noninferiority threshold; the superiority threshold was 54%. RESULTS: A total of 191 of 208 patients who received 12 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 91.8% (97.5% CI, 87.6 to 96.1). A total of 165 of 172 patients who received 24 weeks of treatment had a sustained virologic response at post-treatment week 12, for a rate of 95.9% (97.5% CI, 92.6 to 99.3). These rates were superior to the historical control rate. The three most common adverse events were fatigue (in 32.7% of patients in the 12-week group and 46.5% of patients in the 24-week group), headache (in 27.9% and 30.8%, respectively), and nausea (in 17.8% and 20.3%, respectively). The hemoglobin level was less than 10 g per deciliter in 7.2% and 11.0% of patients in the respective groups. Overall, 2.1% of patients discontinued treatment owing to adverse events. CONCLUSIONS: In this phase 3 trial of an oral, interferon-free regimen evaluated exclusively in patients with HCV genotype 1 infection and cirrhosis, multitargeted therapy with the use of three new antiviral agents and ribavirin resulted in high rates of sustained virologic response. Drug discontinuations due to adverse events were infrequent. Copyright © 2014 Massachusetts Medical Society.


Wittekind C.,University of Leipzig
Pathologe | Year: 2010

In the seventh edition of the TNM Classification of Malignant Tumours there are several entirely new classifications: upper aerodigestive mucosal melanoma, gastrointestinal stromal tumour, gastrointestinal carcinoid (neuroendocrine tumour), intrahepatic cholangiocarcinoma, Merkel cell carcinoma, uterine sarcomas, and adrenal cortical carcinoma. Significant modifications concern carcinomas of the oesophagus, oesophagogastric junction, stomach, appendix, biliary tract, lung, skin, prostate and ophthalmic tumours, which will be not addressed in this article. For several tumour entities only minor changes were introduced which might be of importance in daily practice.The new classifications and changes will be commented on without going into details. © Springer-Verlag 2010.


Beck-Sickinger A.G.,University of Leipzig | Budisa N.,TU Berlin
Angewandte Chemie - International Edition | Year: 2012

The genetic code was expanded with orthogonal pairs to introduce photoactivatable amino acids into G-protein-coupled receptors (GPCRs) in a noninvasive manner. In this way the receptor surface could be mapped by searching for specific ligand interaction sites and the complex dynamics could be studied. This method is also useful for probing the structure of GPCR complexes in living cells. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Braun G.,University of Leipzig | Pokutta S.,Georgia Institute of Technology
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2013

We provide a new framework for establishing strong lower bounds on the nonnegative rank of matrices by means of common information, a notion previously introduced in [1]. Common information is a natural lower bound for the nonnegative rank of a matrix and by combining it with Hellinger distance estimations we can compute the (almost) exact common information of UDISJ partial matrix. We also establish robustness of this estimation under various perturbations of the UDISJ partial matrix, where rows and columns are randomly or adversarially removed or where entries are randomly or adversarially altered. This robustness translates, via a variant of Yannakakis' Factorization Theorem, to lower bounds on the average case and adversarial approximate extension complexity. We present the first family of polytopes, the hard pair introduced in [2] related to the CLIQUE problem, with high average case and adversarial approximate extension complexity. We also provide an information theoretic variant of the fooling set method that allows us to extend fooling set lower bounds from extension complexity to approximate extension complexity. Copyright © 2013 by The Institute of Electrical and Electronics Engineers, Inc.


Valiullin R.,University of Leipzig
AIP Conference Proceedings | Year: 2011

Fundamental understanding of the correlations between the phase state and dynamics of fluids confined to mesoporous solids is an important prerequisite for their optimal use in practical applications. The present contribution describes some recent progress in the exploration of such interrelations using nuclear magnetic resonance. In particular, transport properties of fluids during gas-liquid, solid-liquid and liquid-liquid transitions occurring in pore spaces of mesoporous solids are discussed and are shown to bear strong correlations. From the results presented it will, in particular, become evident that molecular diffusivity is a sensitive microscopic parameter not only to the thermodynamic state of the system, but also the history of its preparation. © 2011 American Institute of Physics.


Meier P.,University of Leipzig
Graefe's Archive for Clinical and Experimental Ophthalmology | Year: 2010

Background: Combined anterior and posterior segment injuries in children require special attention to the unique characteristics of children's eyes, including a pronounced tendency to scar formation and proliferation, adherence of the posterior vitreous, as well as the danger of amblyopia. Methods: This article reviews the current body of literature documenting the main aspects of surgical management, complications, and prognosis of combined anterior and posterior segment injuries in children. Results: For optimal treatment success, special strategies are necessary with regard to: 1) comprehensive secondary operation for internal reconstruction, 2) encircling buckle surgery, 3) management of the lens, 4) use of a temporary keratoprosthesis, 5) endophthalmitis, and 6) late complications, e.g., secondary glaucoma, secondary strabismus, leukoma cornea, and phthisis bulbi. Further crucial prognostic factors were analyzed. Conclusion: Combined anterior and posterior segment injuries in children require optimal surgical treatment management that varies from adult treatment with regard to several essential aspects. Care should be provided by pediatric ophthalmology specialists with orthoptic follow-up as necessary, over many years. © 2010 Springer-Verlag.


Parallel to the recent reneurobiologization of psychiatry as a subject, therapies based on electricity and elektrcomagnetism are returning to mental health care. Around 1880, the application of brain stimulating treatment on patients was particularly popular among German psychiatrists. This fact has largely been ignored in historical psychiatric research as present day practices, in particular deep brain stimulation (DBS), have frequently been seen solely within the tradition of brain surgery. Against this background the present study aims to revive the first trials of non-surgical electrical brain stimulation on depressive and psychotic patients, highlighting a 2-part study published by Wilhelm Tigges. It was Tigges along with Rudolph Gottfried Arndt and Wilhelm Erb who tried to establish clear rules on the most beneficial application methods and doses. Interestingly, Tigges's therapy was successful in cases of severe depression with chronification potential, i.e. precisely the clinical picture for which brain stimulation therapies are reserved today as a last option and ascribed an easing and even curing potential. Trigges also found that electricity produced almost no positive effect whatsoever with madly insane patients and hence anticipated the current non-application of DBS on these patients. After 1890 electrotherapeutic approaches in psychiatry were marginalized, first and foremost as no clear and reliable rules could be verified for their application, nor could their mode of action be fully explained. The success of electrotherapy in psychiatry was also restricted due to limitations of the time, namely (1) electrophysiology only emerging as a discipline, (2) the electrophysical medical apparatus industry only beginning to be established and (3) the lack of generally accepted guidelines and electrotherapy restriction to individual, barely generalizable experience (eclecticism). Present day applications of electricity, mainly DBS, have overcome these problems. © 2012 Springer-Verlag.


Hildebrandt G.,University of Leipzig | Hildebrandt G.,University of Rostock
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis | Year: 2010

It is well established that moderate to high doses of radiation can increase the occurrence also of a variety of non-cancer effects in exposed individuals, but for radiation protection purposes it has generally been assumed that there is a threshold of dose below which no significant non-cancer effects (apart from hereditary disease) arise.In recent years, there is growing epidemiological evidence of excess risk of late occurring cardiovascular disease at much lower radiation doses and occurring over much longer intervals after radiation exposure without a clear cut threshold. However, the epidemiological evidence available so far for non-cancer health effects after exposure to moderate or low radiation doses is suggestive rather than persuasive.The mechanisms of radiation-induced vascular disease induction are far away from being understood. However, it seems to be very likely that inflammatory responses are involved. Recent experimental studies by Stewart et al. [25] could demonstrate that high dose exposure to the cardiovascular system is associated with an earlier onset and accelerated development of macrophage-rich, inflammatory atherosclerotic lesions prone to intra-plaque hemorrhage and may also cause a decrease in myocardial perfusion. Both, macro-vascular and micro-vascular radiation effects involve the endothelium and pro-inflammatory signalling cascades. If modulation of inflammatory response is arguably also the most likely cause of radiation-induced cardiovascular disease after low dose exposure, this also implies a role for non-targeted radiation effects.In the absence of a convincing mechanistic explanation of the currently available epidemiological evidence for radiation-induced cardiovascular risk at low radiation doses, caution is required in the interpretation of the statistical associations. On the other hand, the possibility of such a causal explanation cannot be reliably excluded. Further epidemiological and biological evidence from currently ongoing research projects will allow a firmer conclusion to be drawn. © 2010 Elsevier B.V.


Stingu C.S.,University of Leipzig
Quintessence international (Berlin, Germany : 1985) | Year: 2012

To define and compare the microbiologic profile of subgingival plaque in German patients with periodontitis (including aggressive and advanced chronic periodontitis) and healthy subjects and to determine significant association between isolates and clinical status. Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythia are major periodontal pathogens, though it is recognized that other species may also contribute to the pathogenesis of periodontal disease. Thirty-three patients with clinical and radiologic proof of aggressive and advanced chronic periodontitis and 20 healthy subjects were enrolled in this study. Clinical indices were recorded as six-point measurements on each tooth. Samples of the subgingival plaque were taken with paper points from four teeth of each individual. The samples were divided into two parts. One part was immediately cultivated, while the other one was stored at -20°C until analyzed by real-time polymerase chain reaction. A total of 284 anaerobic isolates (224 isolates from patients and 60 isolates from healthy controls) were identified. Forty different anaerobic species were isolated, with a mean of 6.78 species per patient and 3 species per healthy control subject. Significant differences in prevalence (after adjusting for multiple comparisons, P < .001) were found for Prevotella intermedia and nigrescens, Fusobacterium nucleatum, T forsythia, Treponema denticola, and Veillonella parvula. The first four species were associated with the aggressive periodontitis group and V parvula with healthy subjects. When compared with healthy controls, the microbial profile of subgingival plaque from periodontitis was found to contain known periodontal pathogens with a different prevalence to that described in earlier studies. P intermedia/nigrescens, F nucleatum, T forsythia, and T denticola have been found in lower proportions and small quantities in healthy subjects.


Geue K.,University of Leipzig
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation | Year: 2014

Over the last years, adolescents and young adults with cancer (AYA) have moved strongly into scientific focus. However, there have only been a few studies about the quality of life of the AYA group, and gender differences have very rarely been examined. A cross-sectional study was conducted with young adult cancer patients who were aged 18-39 years at the time of survey and had completed their acute treatment. We used the quality of life questionnaire European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). The EORTC QLQ-C30 contains five function scales (physical, role, emotional, cognitive and social), nine symptom scales and a global quality of life scale. The patient sample was compared to a gender- and age-matched representative sample (REP). Compared to the general population (N = 585), significantly poorer quality of life (p = .001) was observed for the 117 young cancer patients (40 male, 77 female) on all scales and items of the EORTC QLQ-C30. Analyses of variance with the factors group (AYA vs. REP) and gender showed interaction effects for the physical (p < .012), emotional (p < .029) and cognitive function scales (p < .008) and fatigue (p < .026) as well as for the items insomnia (p < .011), constipation (p < .037) and financial difficulties (p < .026). The pattern of the interaction was that female cancer patients reported the lowest quality of life outcomes. The same effects were found for the three calculated sum scales function, symptom and total. Results clearly indicate that young adult cancer patients have a reduced quality of life in comparison with the general population even long after the treatment of their disease is complete. Women had a lower quality of life than men. Age-specific interventions should be offered that lead to improvements in quality of life for this age group. And future studies should clarify what factors lead to women's quality of life being worse than men's.


Hansen T.C.,Laue Langevin Institute | Kohlmann H.,University of Leipzig
Zeitschrift fur Anorganische und Allgemeine Chemie | Year: 2014

In situ neutron powder diffraction is a very convenient tool for the investigation of chemical reactions, whenever crystalline solids are involved. It may give insight into reaction pathways, thus allowing for strategic synthesis planning, revealing particular intermediate steps and quantifying the reaction kinetics. Although the method is rather straightforward, one is bound to a small number of available neutron sources and the few sufficiently high intensity powder diffractometers there, most of which are briefly described herein. The high penetration depth of thermal neutrons allows for a large range of complex sample environments; however neutron absorption and parasitic scattering have to be carefully considered in the construction of dedicated in situ equipment. Some specific types of sample environment, specially designed for in situ neutron powder diffraction will be discussed such as electrochemical cells, autoclaves for the study of solvothermal reactions, and gas-solid reaction cells. Several examples from inorganic chemistry are being presented, ranging from metal hydrides, nitrides, oxides, and halides, to intermetallic compounds or metal organic frameworks, many of them of importance in applications, e.g. in lithium ion batteries, as magnetic or hard materials, high strength alloys, hydrogen storage, ferroelectric or superconducting materials, or as solid catalysts. In situ neutron powder diffraction often paves the way to a better reaction control in chemical synthesis, to the discovery of metastable compounds or gives insight into technologically relevant processes. These successful applications in inorganic chemistry demonstrate the usefulness of the method of in situ neutron powder diffraction and may encourage the reader to consider neutron diffraction in the repertoire of analytic tools. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Schomerus G.,University of Greifswald | Matschinger H.,University of Leipzig | Angermeyer M.C.,University of Cagliari | Angermeyer M.C.,Center for Public Mental Health
Psychological Medicine | Year: 2014

Background. There is an ongoing debate whether biological illness explanations improve tolerance towards persons with mental illness or not. Several theoretical models have been proposed to predict the relationship between causal beliefs and social acceptance. This study uses path models to compare different theoretical predictions regarding attitudes towards persons with schizophrenia, depression and alcohol dependence. Method. In a representative population survey in Germany (n=3642), we elicited agreement with belief in biogenetic causes, current stress and childhood adversities as causes of either disorder as described in an unlabelled case vignette. We further elicited potentially mediating attitudes related to different theories about the consequences of biogenetic causal beliefs (attribution theory: onset responsibility, offset responsibility; genetic essentialism: differentness, dangerousness; genetic optimism: treatability) and social acceptance. For each vignette condition, we calculated a multiple mediator path model containing all variables. Results. Biogenetic beliefs were associated with lower social acceptance in schizophrenia and depression, and with higher acceptance in alcohol dependence. In schizophrenia and depression, perceived differentness and dangerousness mediated the largest indirect effects, the consequences of biogenetic causal explanations thus being in accordance with the predictions of genetic essentialism. Psychosocial causal beliefs had differential effects: belief in current stress as a cause was associated with higher acceptance in schizophrenia, while belief in childhood adversities resulted in lower acceptance of a person with depression. Conclusions. Biological causal explanations seem beneficial in alcohol dependence, but harmful in schizophrenia and depression. The negative correlates of believing in childhood adversities as a cause of depression merit further exploration. Copyright © Cambridge University Press 2013.


McNeill S.A.,Western General Hospital | Good D.W.,Western General Hospital | Stewart G.D.,Western General Hospital | Stolzenburg J.-U.,University of Leipzig
BJU International | Year: 2014

Objective To determine the 5-year oncological outcomes of endoscopic extraperitoneal radical prostatectomy (EERPE) from a medium-volume centre, thereby providing much needed data on outcomes from the UK. Patients and Methods From January 2006 to January 2012, 575 patients underwent EERPE for localized prostate cancer, performed by a single surgeon who had completed a modular training programme. Follow-up was as per local hospital policy and data were collected in our prospective database. A retrospective review of patient demographics, prostate-specific antigen (PSA) levels, pathological T stages, Gleason scores, surgical margin status and biochemical recurrence (BCR) data was performed. BCR was defined as PSA >0.2 μg/L. Results The mean (range) patient age was 62 (40.3-76.5) years and the mean (range) follow-up was 30 (12-72) months. The median (interquartile range [IQR]) operating time was 135 (120-170) min and the median (IQR) blood loss was 200 (100-250) mL. Of the 575 patients, 135 (23.5%) had positive surgical margins (PSMs). The PSM rate for pT2 disease was 66/406 patients (16.3%) and for pT3 disease it was 68/168 patients (40.5%). Overall BCR-free survival at 5-years was 81.5%. Multivariate Cox analysis showed that PSMs, Gleason score, D'Amico risk category and pT stage were independent predictors of BCR-free survival. Conclusions This assessment of the oncological results of EERPE, which included the surgical learning curve, shows that the adoption of EERPE after mentored fellowship training translates into mid-term oncological outcomes in line with those of retropubic/ transperitoneal laparoscopic approaches and with large-volume centres worldwide which have pioneered laparoscopic radical prostatectomy. The study shows that EERPE in a medium-volume second generation laparoscopic centre (that introduced EERPE after adequate training in pioneering centres) produces results with good 5-year oncological outcomes, similar to those of other major series, for patients in the UK. © 2013 The Authors. BJU International © 2013 BJU International.


Edler T.,University of Gottingen | Mayr S.G.,University of Leipzig
Advanced Materials | Year: 2010

Two complementary lift-off approaches for thin films from MgO, based on standard chemicals, are reported. Accompanied by appropriate annealing treatments they can be employed to synthesize freestanding single crystalline Fe-Pd films in the face centered tetragonal martensitic phase required for miniaturized magnetic shape memory acutation. Generalizations to other materials systems, e.g. epitaxially grown martensitic Ni-Mn-Ga magnetic shape memory alloy films, are also demonstrated. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Bordag M.,University of Leipzig
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

We consider a flat lattice of dipoles modeled by harmonic oscillators interacting with the electromagnetic field in the dipole approximation. Eliminating the variables from the coupled equations of motion, we come to effective Maxwell equations. These allow for taking the lattice spacing a to zero. As a result, we obtain reflection coefficients for the scattering of electromagnetic waves off the sheet. These are a generalization of that known from the hydrodynamic model. For instance, we get a nontrivial scattering for polarizability perpendicular to the sheet. Also, we show that the case of polarizability parallel to the sheet can be obtained in a natural way from a plasma layer of finite thickness. As an alternative approach, we discuss the elimination of the electromagnetic fields resulting in effective equations for the oscillators. These are shown, for a→0, divergent behavior, resulting from the electrostatic interaction of the dipoles. © 2014 American Physical Society.


Background. Cutaneous reactions to drugs can be subdivided in different ways. In addition to the standard classification according to the etiopathogenesis there are also classifications based predominantly on morphological criteria. The majority of drug-related cutaneous adverse reactions are immunological reactions which are collectively classified under the term hypersensitivity. These reactions are based on drug-specific immunoglobulin E (IgE) or cell-mediated mechanisms, not on the mechanism of action of the drug and are unpredictable. Delayed type reactions to drugs are forms of type IV T-cell mediated hypersensitivity. A prerequisite is a stable association of a pharmaceutical substance with a protein so that hapten-protein conjugates can be produced. The most common clinical symptom is maculopapular (morbilliform) drug-related exanthema. This article also examines lichen planus like drug reaction and drug-induced (hematogenic) allergic contact dermatitis in more detail. Diagnostics. The diagnostics are never trivial but also include the differentiation from viral exanthema and initial phases of severe cutaneous adverse reactions, such as toxic epidermal necrolysis. In addition to the morphological classification, the final diagnosis encompasses the interpretation of histopathological alterations in the skin biopsy, analysis of patient medication history, laboratory results and inclusion of data from the literature. Patch tests can also have additional diagnostic benefits. In vitro tests which involve the cellular incubation of the drug responsible should be reserved for specialized laboratories. A prerequisite for successful treatment is immediate termination of the drug responsible. Therapy and prognosis. Therapy is symptomatic with topical and also short-term systemic steroids and antihistamines. The prognosis is very good. © 2014 Springer-Verlag.


Bluher M.,University of Leipzig
Deutsche Medizinische Wochenschrift | Year: 2014

Obesity belongs to the five most important health burdens in modern societies and reaches with ~20 % prevalence in Germany epidemic proportions. Obesity significantly increases the risk of developing metabolic (e. g. type 2 diabetes), cardiovascular, orthopaedic, psychologic and other disorders. Despite the well established epidemiologic relationship between obesity and these co-morbidities, there is a subgroup of metabolically healthy obese patients, which seems to be protected against metabolic and cardiovascular obesity related disorders. Compared to metabolically unhealthy or high risk obese patients, metabolically healthy obese individuals are characterized by preserved insulin sensitivity, lower liver fat content, lower visceral fat mass, as well as normal adipose tissue function. Noteworthy, metabolically healthy obese individuals do not significantly improve their obesity-associated risk for the development of type 2 diabetes and vascular diseases. Therefore, distinction between metabolically healthy from high-risk obese phenotypes will facilitate the identification of the obese person who will benefit the most from early lifestyle, pharmacological or bariatric surgery interventions. A stratified treatment approach considering these different obesity phenotypes should be introduced into clinical management of obese patients. © Georg Thieme Verlag KG.


Diastolic dysfunction (DD) was identified as a predictor of adverse prognosis in heart failure with reduced ejection fraction (HFREF). It is, however, unknown if DD is improved by exercise training, which is known to induce reverse remodelling, and if the training effect is attenuated in elderly HFREF patients. We therefore assessed DD in a cohort of referent controls (RCs) and HFREF patients and studied the response of DD to endurance exercise in two age groups (≤55 years and ≥65 years). Sixty RC (30 ≤ 55 years, mean age 50 ± 5 years; 30 ≥ 65 years, 72 ± 4 years) and 60 HFREF patients (30 ≤ 55 years, 46 ± 5 years; 30 ≥ 65 years, 72 ± 5 years, EF 28 ± 5%) were randomized to 4 weeks of supervised endurance training or to a control group. Exercise training was effective in reducing LV isovolumetric relaxation time by 29% in young and by 26% in old HFREF patients (P< 0.05 for both). As assessed by tissue Doppler, septal E' increased by 37% in young and by 39% among old HFREF patients (P< 0.005 for both) resulting in a significant decrease in the E/E' ratio from 13 ± 1 to 10 ± 1 in young and 14 ± 1 to 11 ± 1 in old HFREF patients (P< 0.05 for both). Serum levels of N-terminal pro brain natriuretic peptide were significantly reduced after endurance training in HFREF patients of all ages. In HFREF, diastolic function is significantly impaired in all age groups. Endurance training is highly effective in improving left ventricular diastolic function in HFREF patients regardless of age. This study is registered at ClinicalTrials.gov (number: NCT00176319).


The determination of the collagen and glycosaminoglycan (GAG) contents of native and particularly bioengineered tissues is of considerable interest because the collagen-to-GAG ratio determines the water content of the tissue, which is crucial regarding its mechanical properties. (1)H NMR spectroscopy subsequent to the hydrolysis of the sample by aqueous 6 M DCl at 353 K is used to determine the GAG and collagen contents simultaneously. Under these strongly acidic conditions the biopolymers of the extracellular matrix, collagen, and GAG are fragmented into their individual monomers, that is, free amino acids from collagen and monosaccharides from the polymer repeat units of GAGs. The amino acid amount can be easily determined in the presence of an internal standard by (1)H NMR spectroscopy because amino acids proved to be stable under acidic conditions. The carbohydrates are subject to charring in the presence of concentrated DCl, but glucosamine and galactosamine were found to be sufficiently stable for quantification under the chosen conditions.


Paschke R.,University of Leipzig
Langenbeck's Archives of Surgery | Year: 2011

Introduction: Familial clustering of goiters mostly with an autosomal dominant pattern of inheritance has repeatedly been reported. Moreover, other environmental and etiologic factors are likely to be involved in the development of euthyroid goiter. Therefore, a multifactorial etiology based on complex interactions of both genetic predisposition and the individuals' environment is likely. Methods: The line of events from early thyroid hyperplasia to multinodular goiter argues for the predominant neoplastic (i.e., originating from a single mutated cell) character of nodular structures. Etiologically, relevant somatic mutations are known in two thirds of papillary and follicular thyroid carcinomas and hot thyroid nodules. In contrast, the somatic mutations relevant for benign cold or benign isocaptant thyroid nodules which constitute the majority of thyroid nodules are unknown. Results: The nodular process is triggered by the oxidative nature of thyroid hormone synthesis or additional oxidative stress caused by iodine deficiency or smoking. If the antioxidant defense is not effective, this oxidative stress will cause DNA damage followed by an increase of the spontaneous mutation rate which is a substrate for tumorogenesis. Conclusions: Therefore, the hallmark of thyroid physiology-H 2O 2 production during hormone synthesis-is very likely the ultimate cause for the frequent mutagenesis in the thyroid gland. Because iodine deficiency increases the oxidative burden, DNA damage and mutagenesis could provide the basis for the frequent nodular transformation of endemic goiters. © 2011 Springer-Verlag.


Zauner T.,University of Leipzig
Analytical chemistry | Year: 2011

Proteases are widely used in analytical sciences and play a central role in several widespread diseases. Thus, there is an immense need for highly adaptable and sensitive assays for the detection and monitoring of various proteolytic enzymes. We established a simple protease fluorescence resonance energy transfer (pro-FRET) assay for the determination of protease activities, which could in principle be adapted for the detection of all proteases. As proof of principle, we demonstrated the potential of our method using trypsin and enteropeptidase in complex biological mixtures. Briefly, the assay is based on the cleavage of a FRET peptide substrate, which results in a dramatic increase of the donor fluorescence. The assay was highly sensitive and fast for both proteases. The detection limits for trypsin and enteropeptidase in Escherichia coli lysate were 100 and 10 amol, respectively. The improved sensitivity for enteropeptidase was due to the application of an enzyme cascade, which leads to signal amplification. The pro-FRET assay is highly specific as even high concentrations of other proteases did not result in significant background signals. In conclusion, this sensitive and simple assay can be performed in complex biological mixtures and can be easily adapted to act as a versatile tool for the sensitive detection of proteases.


Mierke C.T.,University of Leipzig | Mierke C.T.,Friedrich - Alexander - University, Erlangen - Nuremberg
Cell Biochemistry and Biophysics | Year: 2013

Cell invasion through the extracellular matrix (ECM) of connective tissue is an important biomechanical process, which plays a prominent role in tumor progression. The malignancy of tumors depends mainly on the capacity of cancer cells to migrate and metastasize. A prerequisite for metastasis is the invasion of cancer cells through connective tissue to targeted organs. Cellular stiffness and cytoskeletal remodeling dynamics have been proposed to affect the invasiveness of cancer cells. Here, this study investigated whether highly invasive cancer cells are capable of invading into dense 3D-ECMs with an average pore-size of 1.3 or 3.0 μm when phagocytized beads (2.7 and 4.5 μm diameter) increased their cellular stiffness and reduced their cytoskeletal remodeling dynamics compared to weakly invasive cancer cells. The phagocytized beads decreased the invasiveness of the α5β1high cancer cells into 3D-ECMs, whereas the invasiveness of the α5β1low cancer cells was not affected. The effect of phagocytized beads on the highly invasive α5β1high cells was abolished by specific knock-down of the α5 integrin subunit or addition of an anti-α5 integrin blocking antibody. Furthermore, the reduction of contractile forces using MLCK and ROCK inhibitors abolished the effect of phagocytized beads on the invasiveness of α5β1high cells. In addition, the cellular stiffness of α5β1high cells was increased after bead phagocytosis, whereas the bead phagocytosis did not alter the stiffness of α5β1low cells. Taken together, the α5β1 integrin dependent invasiveness was reduced after bead phagocytosis by altered biomechanical properties, suggesting that the α5β1high cells need an appropriate intermediate cellular stiffness to overcome the steric hindrance of 3D-ECMs, whereas the α5β1low cells were not affected by phagocytized beads. © 2013 Springer Science+Business Media New York.


Choffrut A.,University of Leipzig
Archive for Rational Mechanics and Analysis | Year: 2013

In Dissipative Euler Flows and Onsager's Conjecture. arxiv.1205.3626, preprint, 2012, De Lellis and Székelyhidi construct Hölder continuous, dissipative (weak) solutions to the incompressible Euler equations in the torus T3. The construction consists of adding fast oscillations to the trivial solution. We extend this result by establishing optimal h-principles in two and three space dimensions. Specifically, we identify all subsolutions (defined in a suitable sense) which can be approximated in the H-1-norm by exact solutions. Furthermore, we prove that the flows thus constructed on T3 are genuinely three-dimensional and are not trivially obtained from solutions on T2. © 2013 Springer-Verlag Berlin Heidelberg.


In 2013 at the Rodewisch Clinic for Psychiatry, four folders were found that contain original documents from the office of former head of the clinic Rolf Walther. These original sources provide new insights into the organisational background of the International Symposium on Psychiatric Rehabilitation of 1963, as a result of which the groundbreaking Rodewisch Propositions were framed. The documents founds reveal that, apart from the persons already identified, Halle/Saale - based hygienist Karlheinz Renker was deeply involved in the preparation of this event. They also show that for ideological reasons the GDR Ministry of Health restricted the number of participants from non-socialist countries, in particular Western Germany, to be admitted. Finally, the sources suggest that a volume compiling all talks given at the symposium as one publication and as such making its content and resolutions known to a wider public failed, among other reasons, due to the fact that Karl Leonhard, then head of the GDR Association for Psychiatry and Neurology, was not interested in it. © Georg Thieme Verlag KG Stuttgart, New York.


Stein C.,Free University of Berlin | Baerwald C.,University of Leipzig
Expert Opinion on Pharmacotherapy | Year: 2014

Introduction: Centrally acting opioids are well established in the treatment of acute, surgical and cancer pain. However, their use in chronic noncancer pain (CNCP) is controversial because of side effects such as tolerance, somnolence, respiratory depression, confusion, constipation and addiction. Chronic arthritis and other musculoskeletal diseases are among the leading causes of CNCP. Areas covered: This manuscript will discuss the role of conventional opioids in chronic arthritis. In addition, future developments and strategies exploiting peripheral effects of opioids on pain and inflammation will be outlined. Expert opinion: Aims in drug development include the design of peripherally restricted opioid agonists, selective targeting of endogenous opioids to sites of painful injury and the augmentation of peripheral ligand and receptor synthesis, for example, by gene therapy. Although a large number of peripherally acting opioid compounds have been developed, clinical Phase III studies have not been published so far. Another strategy is to augment the effects of endogenously released opioid peptides by the inhibition of their degrading enzymes. Technology-oriented research is needed to find novel ways of peripheral restriction of opioids. Such analgesics would be desirable for their lack of central side effects and of adverse effects typical of nonsteroidal anti-inflammatory drugs (gastrointestinal ulcers, bleeding, myocardial infarction and stroke). © Informa UK, Ltd.


Bosmans J.,University of Antwerp | Bleiziffer S.,TU Munich | Gerckens U.,Gemeinschaftskrankenhaus | Wenaweser P.,University of Bern | And 3 more authors.
Journal of the American College of Cardiology | Year: 2015

Background Transcatheter aortic valve replacement (TAVR) enables treatment of high-risk patients with symptomatic aortic stenosis without open-heart surgery; however, the benefits are mitigated by the potential for neurological events. Objectives This study sought to determine the timing and causes of clinically relevant neurological events after self-expandable TAVR. Methods We enrolled 1,015 patients, of whom 996 underwent TAVR with a self-expandable system at 44 TAVR-experienced centers in Europe, Colombia, and Israel. Neurological events were evaluated for 3 distinct time periods: periprocedural (0 to 1 days post TAVR); early (2 to 30 days); and late (31 to 730 days). In this real-world study, neurological events were first referred to the site neurologist and then reviewed by an independent neurologist. Results The overall stroke rate was 1.4% through the first day post-procedure, 3.0% at 30 days, and 5.6% at 2 years. There were no significant predictors of periprocedural stroke or stroke/transient ischemic attack (TIA) combined. Significant predictors of early stroke were acute kidney injury (p = 0.03), major vascular complication (p = 0.04), and female sex (p = 0.04). For stroke/TIA combined, prior atrial fibrillation (p = 0.03) and major vascular complication (p = 0.009) were predictive. Coronary artery bypass graft surgery was the only significant predictor of late stroke (p = 0.007) or late stroke/TIA (p = 0.06). Conclusions Treatment of high-risk patients with aortic stenosis using a self-expandable system was associated with a low stroke rate at short- and long-term follow-up. Multivariable predictors of clinically relevant neurological events differed on the basis of the timing after TAVR. (CoreValve Advance International Post Market Study; NCT01074658) © 2015 American College of Cardiology Foundation.


Godo L.,University of Barcelona | Gottwald S.,University of Leipzig
Fuzzy Sets and Systems | Year: 2015

The paper discusses the relationship between fuzzy sets and formal logics as well as the influences fuzzy set theory had on the development of particular formal logics. Our focus is on the historical side of these developments. © 2015 Elsevier B.V. All rights reserved.


Mierke C.T.,University of Leipzig
Reports on Progress in Physics | Year: 2014

The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in particular the understanding of mechano-coupling and mechano-regulating functions in cell invasion, appears as an important step in cancer progression and inflammatory response to injuries. This may lead to novel insights into cancer disease and inflammatory diseases and will overcome classical views on cancer and inflammation. In addition, this review will discuss how the physics of cancer and inflammation can help to reveal whether cancer cells will invade connective tissue and metastasize or how leukocytes extravasate and migrate through the tissue. In this review, the physical concepts of cancer progression, including the tissue basement membrane a cancer cell is crossing, its invasion and transendothelial migration as well as the basic physical concepts of inflammatory processes and the cellular responses to the mechanical stress of the microenvironment such as external forces and matrix stiffness, are presented and discussed. In conclusion, this review will finally show how physical measurements can improve classical approaches that investigate cancer and inflammatory diseases, and how these physical insights can be integrated into classical tumor biological approaches. © 2014 IOP Publishing Ltd.


Pugach I.,Max Planck Institute for Evolutionary Anthropology | Matveyev R.,University of Leipzig | Wollstein A.,University of Cologne | Wollstein A.,Erasmus University Rotterdam | And 2 more authors.
Genome Biology | Year: 2011

We describe a PCA-based genome scan approach to analyze genome-wide admixture structure, and introduce wavelet transform analysis as a method for estimating the time of admixture. We test the wavelet transform method with simulations and apply it to genome-wide SNP data from eight admixed human populations. The wavelet transform method offers better resolution than existing methods for dating admixture, and can be applied to either SNP or sequence data from humans or other species. © 2011 Pugach et al.; licensee BioMed Central Ltd.


Philippi-Hohne C.,University of Leipzig
Best Practice and Research: Clinical Anaesthesiology | Year: 2011

The incidence of childhood obesity ranges today from approximately 8% to 17%, and is an increasing issue in developed and developing countries. This disease will become increasingly significant in paediatric anaesthesia. Obese children not only have anaesthesia-relevant co-existing diseases, that are, asthma and hypertension, but also have a higher incidence of anaesthesia-related complication. This review covers current definition and some epidemiology of childhood obesity. It summarises potential co-morbidities and provides details for preoperative evaluation, anaesthetic management and prevention of perioperative complications. © 2011 Elsevier Ltd. All rights reserved.


Misfeld M.,University of Leipzig | Brereton R.J.L.,University of Sydney | Sweetman E.A.,University of Sydney | Doig G.S.,University of Sydney
Journal of Thoracic and Cardiovascular Surgery | Year: 2011

Objective: Neurologic complications after coronary artery bypass grafting remain a concern. Off-pump coronary artery bypass grafting is a surgical strategy proposed to decrease this risk. Use of an off-pump anaortic technique, which leaves the ascending aorta untouched, may result in further reductions. This systematic review of all published evidence compares neurologic complications after anaortic off-pump coronary artery bypass grafting versus that with aortic manipulation. Methods: PubMed and Embase were searched up to August 2008. Experts were contacted, and reference lists of retrieved articles were hand searched. The search process was not limited to English-language sources. Observational studies comparing standard off-pump coronary artery bypass grafting technique with anaortic technique were eligible for inclusion if they reported neurologic complications (stroke and transient ischemic attack). Meta-analysis was conducted to assess differences between groups with regard to neurologic complications. Results: Electronic search identified 1428 abstracts, which resulted in retrieval and detailed review of 331 full-text articles. Eight observational studies reported neurologic complications in 5619 anaortic off-pump coronary artery bypass grafting cases and 5779 cases with aortic manipulation. Postsurgical neurologic complications were significantly lower in anaortic off-pump coronary artery bypass grafting cases (odds ratio, 0.46; 95% confidence interval, 0.29-0.72; I2 = 0.8%; P = .0008). Conclusions: Avoidance of aortic manipulation during off-pump coronary artery bypass grafting decreases neurologic complications relative to standard technique in which the ascending aorta is manipulated. In patients at high risk for stroke or transient ischemic attack, we recommend avoidance of aortic manipulation during off-pump coronary artery bypass grafting. Copyright © 2011 by The American Association for Thoracic Surgery.


Verlohren S.,Charite - Medical University of Berlin | Stepan H.,University of Leipzig | Dechend R.,Experimental and Clinical Research Center
Clinical Science | Year: 2012

The pathogenesis of pre-eclampsia is still not completely known; however, in the recent decade, there have been tremendous research efforts leading to impressive results highlighting the role of a disturbed angiogenic balance as one of the key features of the disease. Numerous studies have shown the key role of the placenta in the pathogenesis of pre-eclampsia. A shift in the sFlt-1 (soluble Fms-like tyrosine kinase-1)/PlGF (placental growth factor) ratio is associated with the disease. Although pre-eclampsia seems to be a clearly defined disease, clinical presentation, and particularly the dynamics of the clinical course, can vary enormously. The only available tools to diagnose pre-eclampsia are blood pressure measurement and urine protein sampling. However, these tools have a low sensitivity and specificity regarding the prediction of the course of the disease or maternal and perinatal outcomes. The only cure for the disease is delivery, although a timely diagnosis helps in decreasing maternal and fetal morbidity and mortality. The sFlt1/PlGF ratio is able to give additional valuable information on the status and progression of the disease and is apt to be implemented in the diagnostic algorithm of pre-eclampsia. In the present review, we aim to provide an overview of the vast literature on angiogenesis and anti-angiogenesis factors in pre-eclampsia that have been published over the last decade. We introduce work from basic research groups who have focused on the pathophysiological basis of the disease. Furthermore, we review studies with a clinical focus in which the sFlt-1/PlGF ratio has been analysed along with other candidates for routine clinical assessment of pre-eclampsia. © The Authors Journal compilation. © 2012 Biochemical Society.


Current guidelines recommend thrombus aspiration in patients with ST-elevation myocardial infarction (STEMI); however, there are insufficient data to unequivocally support thrombectomy in patients with non-STEMI (NSTEMI). The TATORT-NSTEMI (Thrombus Aspiration in ThrOmbus containing culpRiT lesions in Non-ST-Elevation Myocardial Infarction) trial is a prospective, controlled, multicenter, randomized, open-label trial enrolling 460 patients. The hypothesis is that, against a background of early revascularization, adjunctive thrombectomy leads to less microvascular obstruction (MO) compared with conventional percutaneous coronary intervention (PCI) alone, as assessed by cardiac magnetic resonance imaging (CMR) in patients with NSTEMI. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary endpoint is the extent of late MO assessed by CMR. Secondary endpoints include early MO, infarct size, and myocardial salvage assessed by CMR as well as enzymatic infarct size and angiographic parameters, such as thrombolysis in myocardial infarction flow post-PCI and myocardial blush grade. Furthermore, clinical endpoints including death, myocardial re-infarction, target vessel revascularization, and new congestive heart failure will be recorded at 6 and 12 months. Safety will be assessed by the incidence of bleeding and stroke. The TATORT-NSTEMI trial has been designed to test the hypothesis that thrombectomy will improve myocardial perfusion in patients with NSTEMI and relevant thrombus burden in the culprit vessel reperfused by early PCI. The trial is registered under http://www.clinicaltrials.gov: NCT01612312.


This study represents a small-scale approach to forest structure and biomass in the Atlantic Rainforest in Brazil and provides information on an ecosystem in which there still is a lack of data in this regard. The project was carried out in the National Park " Serra dos Orgãos" in the state of Rio de Janeiro, which is one of the largest remnants of continuous forest in this area. This forest is marked by a mosaic of forest types differing in tree composition and structure. Within this heterogeneous habitat the stand structure in three investigation plots was assessed to estimate the above-ground dry biomass (AGB) for all trees with a dbh ≥ 5. cm. This study indicates the structural diversity of the Atlantic Rainforest. Trees with a dbh > 30. cm were represented by 6% of all sampled individuals (18 out of 318 trees), but contributed 72% of total estimated AGB. The results suggest that big trees in the Atlantic Rainforest may contribute more into total AGB as reported for other tropical rainforests. Small-scale structural approaches like this study are able to form an initiating framework of more detailed results and help to improve estimates on biomass amounts and therefore on carbon storage capacity. © 2010 Elsevier B.V.


Reich S.,RWTH Aachen | Schierz O.,University of Leipzig
Clinical Oral Investigations | Year: 2013

Objectives: The objective of this prospective clinical study was to evaluate the performance of chair-side generated crowns after 48 months. Materials and methods: Forty-one posterior full contour crowns made of a machinable lithium disilicate ceramic (e.max CAD LT) were inserted in 34 patients applying a chair-side CAD/CAM technique. One crown per patient was randomly selected for evaluation at baseline, after 6, 12, 24, 36, and 48 months according to modified US Public Health Service criteria. Results: After a mean observation time of 51 months (min, 48 months; max, 56 months; SD ± 2.3 months), 29 crowns were available for re-examination. Within the observation period, one failure occurred due to a crown fracture after 2.8 years. Four abutment teeth revealed signs of biological complications: Two abutment changed sensibility perception from positive to negative within the first 13 month. Two abutment teeth showed secondary caries below the crown margin, one after the 24, and another after the 48 month recall. Both abutments received cervical adhesive composite fillings. The failure-free rate was 96.3 % after 4 years according to Kaplan-Meier (CI: upper bound, 4.4 years; lower bound, 4.7 years). Conclusions: Due to the fact that the secondary caries was not caused as a result of an inaccuracy of the crown margins and the endodontic complications were in a normal range, the clinical performance of the crowns was completely satisfying. Clinical relevance: The chair-side application of lithium disilicate crowns can be recommended. © 2012 Springer-Verlag Berlin Heidelberg.


Kunz M.,University of Leipzig
JDDG - Journal of the German Society of Dermatology | Year: 2013

Activated intracellular signaling pathways based on mutations in oncogenes and tumor suppressor genes play an important role in a variety of malignant tumors. In dermatology, such mutations have been identified in melanoma, basal cell carcinoma and squamous cell carcinoma. These have partly led to the establishment of new, targeted therapies. Treatment successes have been particularly impressive for melanoma with small molecule inhibitors directed against the mutated BRAF oncogene and in basal cell carcinoma with inhibitors directed against the hedgehog signaling pathway. New sequencing technologies, in particular next generation sequencing, have led to a better and more comprehensive understanding of malignant tumors. This approach confirmed the pathogenic role of BRAF, NRAS and MAP kinase pathways for melanoma. At the same time, a series of further interesting target molecules with oncogenic mutations such as ERBB4, GRIN2A, GRM3, PREX2, RAC1 and TP53 were identified. New aspects have recently been shown for squamous cell carcinoma by detection of mutations in the NOTCH signaling pathway. A better understanding of the pathogenesis of these and other tumors should lead to improved and maybe even individualized treatment. The current developments in dermatological oncogenetics based on the new sequencing technologies are reviewed. © The Author | Journal compilation © Blackwell Verlag GmbH, Berlin.


Huster D.,University of Leipzig
Annals of the New York Academy of Sciences | Year: 2014

Wilson's disease (WD) is caused by ATP7B mutations and results in copper accumulation and toxicity in liver and brain tissues. The specific mechanisms underlying copper toxicity are still poorly understood. Mouse models have revealed new insights into pathomechanisms of hepatic WD. Mitochondrial damage is observed in livers of WD patients and in mouse models; copper induces fragmentation of mitochondrial membrane lipids, particularly cardiolipin, with deleterious effects on both mitochondrial integrity and function. Copper accumulation also induces chronic inflammation in WD livers, which is followed by regeneration in parts of the liver and occasionally neoplastic proliferation. Gene expression studies using microarrays have aided our understanding of the molecular basis of these changes. Copper overload alters cholesterol biosynthesis in hepatocytes resulting in reduced liver and serum cholesterol. Experiments are currently underway to elucidate the link between copper and cholesterol metabolism. These findings may facilitate the development of specific therapies to ameliorate WD progression. © 2014 New York Academy of Sciences.


Eitel C.,University of Leipzig
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology | Year: 2013

Experiences with novel oral anticoagulants (NOACs) early after atrial fibrillation (AF) catheter ablation are limited and show controversial results. We aimed to assess the longer-term safety, efficacy, and acceptance of NOACs in a large real-world cohort of patients presenting for AF catheter ablation. From July 2010 until June 2012, 259 patients undergoing AF catheter ablation were prospectively included. Novel oral anticoagulants were given for at least 3 months post-ablation. Clinical outcome (stroke, thromboembolic events, major bleeding), adverse effects, and drug adherence were assessed at discharge and follow-up. On admission patients were presented with a variety of anticoagulants including 54 patients (21%) already on NOACs prior ablation. After ablation 38% of patients received dabigatran 110 mg, 56% 150 mg, and 6% received rivaroxaban 20 mg. There were four periprocedural thromboembolic and major bleeding complications (1.5%), all in patients without NOACs prior ablation (two on warfarin and two on heparin). During long-term follow-up [311 (199; 418) days] no stroke, systemic embolism, or major haemorrhage could be observed. Uneventful electrical cardioversions and reablation procedures were performed in 27 and 12 patients on dabigatran, respectively. Novel oral anticoagulants were prematurely stopped or switched to another anticoagulant due to side effects or at the preference of the treating general practitioner in 9 and 10 patients, respectively. In this prospective observational study, anticoagulation with NOACs following AF catheter ablation was safe and effective at long-term follow-up. Fast onset of action makes NOACs especially attractive in patients without effective anticoagulation on admission and in patients following periprocedural complications.


Lordick F.,University of Leipzig | Lorenzen S.,TU Munich | Yamada Y.,National Cancer Center Hospital | Ilson D.,Sloan Kettering Cancer Center
Gastric Cancer | Year: 2014

The optimal medical treatment for advanced gastric cancer is currently the source of debate. Cytotoxic treatment has been shown to prolong survival and provide improved symptom control compared with best supportive care alone, but a global standard has not yet been defined. A literature research was undertaken. Results were evaluated by an international author team. The conclusions of this are presented in this paper. Combination chemotherapy with cisplatin and 5-fluorouracil was the preferred first-line chemotherapy, but oxaliplatin has shown equivalent efficacy to cisplatin. Oral fluoropyrimidines, especially S-1 and capecitabine, can substitute for 5-fluorouracil. Modern doublet regimens are preferred in the majority of patients on the basis of a balanced benefit-to-risk ratio. In selected fit and compliant patients, especially those with a high tumor burden or potential secondary resectability, a third drug may be added because triplet chemotherapy led to higher responses rates and enhanced efficacy. However, docetaxel also adds a significant increase in side effects. Monotherapy and early dose modifications should be considered in elderly and infirm patients. Beyond that, our understanding of gastric cancer tumor biology is increasing. In HER2-positive gastric cancer, the addition of the monoclononal anti-HER2 antibody trastuzumab to cisplatin and fluoropyrimidines has prolonged survival duration. Second-line chemotherapy with single agents has now become a proven treatment option. Alternatively, anti-angiogenic treatment with ramucirumab is on the horizon. In conclusion, combination chemotherapy is regarded as the global standard of care for the first-line treatment of advanced gastric cancer. Molecularly targeted treatments are being explored, preferably in combination with a backbone of chemotherapy doublets. © 2013 The International Gastric Cancer Association and The Japanese Gastric Cancer Association.


Obermannova R.,University of Leipzig
Current Opinion in Oncology | Year: 2016

PURPOSE OF REVIEW: The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. RECENT FINDINGS: A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. SUMMARY: Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Lohrey M.,University of Leipzig
Groups, Complexity, Cryptology | Year: 2012

Results on algorithmic problems on strings that are given in a compressed form via straight-line programs are surveyed. A straight-line program is a context-free grammar that generates exactly one string. In this way, exponential compression rates can be achieved. Among others, we study pattern matching for compressed strings, membership problems for compressed strings in various kinds of formal languages, and the problem of querying compressed strings. Applications in combinatorial group theory and computational topology and to the solution of word equations are discussed as well. Finally, extensions to compressed trees and pictures are considered. Keywords. Algorithms for compressed strings, compressed word problems, computational complexity. © de Gruyter 2012.


Goel A.,Zaragoza Logistics Center | Goel A.,University of Leipzig
Computers and Operations Research | Year: 2012

In Canada transport companies must ensure that truck drivers can comply with Canadian Commercial Vehicle Drivers Hours of Service Regulations. Canadian regulations comprise the provisions found in US hours of service regulations as well as additional constraints on the maximum amount of driving and the minimum amount of off-duty time on each day. This paper presents a mixed integer programming formulation and an iterative dynamic programming approach for minimising the duration of truck driver schedules complying with Canadian hours of service regulations. Computational experiments show that schedule durations can be significantly reduced compared with a previously presented approach which only focuses on feasibility. © 2011 Elsevier Ltd. All rights reserved.


Holland J.,University of Cardiff | Hollands S.,University of Leipzig
Classical and Quantum Gravity | Year: 2014

We propose an explanation for the 'unnatural smallness' of the cosmological constant, arguing that the stress-energy tensor of the Standard Model should be given by 〈Tμν〉 = ρvac ημν, with a vacuum energy ρvac that differs from the usual 'dimensional analysis' result by an exponentially small factor associated with non-perturbative effects. We substantiate our proposal by a rigorous analysis of a toy model, namely the two-dimensional Gross-Neveu model. The stress energy operator is constructed concretely via the operator-product-expansion, and the inherent ambiguities in its construction are carefully examined. Our result for the vacuum energy is then obtained from the assumptions that (a) the OPE-coefficients have an analytic dependence on g, which we propose to be a generic feature of QFT, and that (b) the vacuum energy vanishes to all orders in perturbation theory. Our result can also be interpreted as saying that, while the semi-classical Einstein's equation can be fulfilled in Minkowski space at the perturbative level, it cannot at the non-perturbative level. Extrapolating our result from the Gross-Neveu model to the Standard Model, one would expect to find ρvac Λ4e-0(1)g2, where Λ is an energy scale such as Λ = MH, and g is a gauge coupling such as g 2/4π = αEW. Assuming this extrapolation is justified, the exponentially small factor due to non-perturbative effects would explain why this quantity is tiny, instead of strictly zero. © 2014 IOP Publishing Ltd.


Ou Q.,China University of Geosciences | Shu D.,China University of Geosciences | Shu D.,Northwest University, China | Mayer G.,University of Leipzig
Nature Communications | Year: 2012

Cambrian lobopodians are important for understanding the evolution of arthropods, but despite their soft-bodied preservation, the organization of the cephalic region remains obscure. Here we describe new material of the early Cambrian lobopodian Onychodictyon ferox from southern China, which reveals hitherto unknown head structures. These include a proboscis with a terminal mouth, an anterior arcuate sclerite, a pair of ocellus-like eyes and branched, antenniform appendages associated with this ocular segment. These findings, combined with a comparison with other lobopodians, suggest that the head of the last common ancestor of fossil lobopodians and extant panarthropods comprized a single ocular segment with a proboscis and terminal mouth. The lack of specialized mouthparts in O. ferox and the involvement of non-homologous mouthparts in onychophorans, tardigrades and arthropods argue against a common origin of definitive mouth openings among panarthropods, whereas the embryonic stomodaeum might well be homologous at least in Onychophora and Arthropoda. © 2012 Macmillan Publishers Limited.


Baumann L.,University of Leipzig
Biopolymers | Year: 2010

Selective modification of proteins is an important tool to study their function. However, it is still challenging to identify the best position to avoid a loss of activity. By using a 6-nitroveratryl (Nvoc)-modification approach, we facilitate the identification of a potential modification site as Nvoc can be removed in situ by UV irradiation and accordingly allows directly the comparison of the biological activity of the modified and the unmodified protein derived from the same precursor. As a test system, we used stromal cell-derived factor-1 (SDF-1), which is involved in a wide range of physiological functions, mainly hematopoiesis and embryonic organ development. This chemokine is a potential candidate in regenerative medicine because of its capability to attract stem cells to distinct localizations. First, we synthesized the wildtype and the Nvoc-modified C-terminal segments SDF-1(50-68) and studied their secondary structure formation by circular dichroism spectroscopy. By using the intein-mediated purification with a affinity chitin binding tag system, we then expressed the peptide thioester M-[A(49)]-SDF-1(1-49)-MESNA recombinantly, in which the valine at position 49 was replaced by a more suitable alanine residue to allow improved cleavage and ligation. After ligation and refolding, the biological activity was proven in a cell-based inositol phosphate accumulation assay prior and after Nvoc removal, which showed that neither the alanine 49 nor the attached Nvoc group impair the activity of the analog. The study shows that lysine 56 is a potential site to introduce labels site-specifically in SDF-1. 2010 Wiley Periodicals, Inc.


Droste M.,University of Leipzig | Vogler H.,TU Dresden
Theoretical Computer Science | Year: 2012

We show that L-weighted automata, L-rational series, and L-valued monadic second order logic have the same expressive power, for any bounded lattice L and for finite and infinite words. We also prove that aperiodicity, star-freeness, and L-valued first-order and LTL-definability coincide. This extends classical results of Kleene, BchiElgotTrakhtenbrot, and others to arbitrary bounded lattices, without any distributivity assumption that is fundamental in the theory of weighted automata over semirings. In fact, we obtain these results for large classes of strong bimonoids which properly contain all bounded lattices. © 2011 Elsevier B.V. All rights reserved.


Goel A.,Zaragoza Logistics Center | Goel A.,University of Leipzig | Archetti C.,University of Brescia | Savelsbergh M.,CSIRO
Computers and Operations Research | Year: 2012

In September 2008 new regulations for managing heavy vehicle driver fatigue entered into force in Australia. According to the new regulations there is a chain of responsibility ranging from drivers to dispatchers and shippers and thus, carriers must explicitly consider driving and working hour regulations when generating truck driver schedules. This paper presents and studies the Australian Truck Driver Scheduling Problem (AUS-TDSP) which is the problem of determining whether a sequence of locations can be visited within given time windows in such a way that driving and working activities of truck drivers comply with Australian Heavy Vehicle Driver Fatigue Law. © 2011 Elsevier Ltd. All rights reserved.


Chmelik C.,University of Leipzig
Microporous and Mesoporous Materials | Year: 2015

In this study differences in the diffusion characteristics of several small molecules in MOF ZIF-8 were examined. The diffusion data were obtained using the technique of IR microscopy by investigating individual crystals. Most of the primary data were already published separately but are revisited here, complemented with new data and discussed together as a mini-review on the diffusion characteristics. The range of the reported diffusivities covers six orders of magnitude. This study was only possible owing to the particularly wide range of crystal sizes, from 20 up to 300μm, available for the diffusion experiments. Different features in the loading dependencies are identified. They reflect a large variety of mechanisms which dominate the mass transfer within the pores, including window blocking effects and molecular clustering. It is demonstrated that the diffusion characteristics may change significantly if a small molecule like methane diffuses in a mixture with other guests. However, this is not a general feature of the system as for larger molecules like ethane and e