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Erlangen, Germany

Friedrich-Alexander-University Erlangen-Nürnberg better known as FAU is a public research university in the cities of Erlangen and Nuremberg in Bavaria, Germany. The name Friedrich-Alexander comes from the university's first founder Friedrich, Margrave of Brandenburg-Bayreuth, and its benefactor Christian Frederick Charles Alexander, Margrave of Brandenburg-Ansbach.In Germany, traditional liberal arts universities do not usually have an engineering school or department. However, FAU does have a distinct engineering faculty.FAU is the second largest state university in the state Bavaria. It has 5 faculties, 23 departments/schools, 30 clinical departments, 19 autonomous departments, 656 professors, 3,404 members of academic staff and roughly 13,000 employees.In winter semester 2014/15 around 39,085 students enrolled in the university in 239 fields of study, with about 2/3 are studying at the Erlangen campus and the remaining 1/3 at the Nuremberg campus. These statistics putted FAU in the list of top 10 largest universities in Germany.In year 2013, there were 5251 students graduated from the university as well as 663 doctorates and 50 post-doctoral theses registered. Moreover, it received 171 million Euro external funding in the same year, therefore making its one of the strongest third-party funded universities in Germany.In 2006 and 2007, as part of the national excellence initiative, FAU was chosen by the German Research Foundation as one of the winners in the German Universities Excellence Initiative. FAU is also a member of DFG and the Top Industrial Managers for Europe network.In Academic Ranking of World Universities for year 2014, FAU ranked second among German universities in Engineering/Technology and Computer science group for all four ranking parameters TOP, FUN, HiCi and PUB. Wikipedia.

Strebovsky J.,University of Heidelberg | Walker P.,University of Heidelberg | Lang R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dalpke A.H.,University of Heidelberg
FASEB Journal | Year: 2011

Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytoplasmic Janus kinases (Jak) and signal transducer and activator of transcription (STAT) signaling pathways. Previously the authors surprisingly observed that SOCS1 translocated into the nucleus, which was because of the presence of a nuclear localization sequence. This report now hypothesizes that SOCS1 mediates specific functions within the nuclear compartment because it is instantly transported into the nucleus, as shown by photoactivation and live cell imaging in human HEK293 cells. The NFκB component p65 is identified as an interaction partner for SOCS1 but not for other members of the SOCS family. SOCS1 bound to p65 only within the nucleus. By means of its SOCS box domain, SOCS1 operated as a ubiquitin ligase, leading to polyubiquitination and proteasomal degradation of nuclear p65. Thus, SOCS1 limited prolonged p65 signaling and terminated expression of NFκB inducible genes. Using mutants that lack either nuclear translocation or a functional SOCS box, this report identifies genes that are regulated in a manner dependent on the nuclear availability of SOCS1. Data show that beyond its receptor-proximal function in Jak/STAT signaling, SOCS1 also regulates the duration of NFκB signaling within the cell nucleus, thus exerting a heretofore unrecognized function. © FASEB. Source

Nitschke L.,Friedrich - Alexander - University, Erlangen - Nuremberg
Annals of the New York Academy of Sciences | Year: 2015

B cell antigen receptor signaling on B-1 cells is controlled by several inhibitory receptors, including Siglec-G, which is a member of the Siglec (sialic acid-binding immunoglobulin-like lectin) family and inhibits B cell signaling. The inhibitory function of Siglec-G is largely restricted to B-1 cells, as demonstrated by studies of Siglec-G-deficient mice showing a phenotype affecting mostly B-1 cells. Siglec-G-deficient mice show a markedly increased B-1a cell population, enhanced B-1 cell signaling, and a shift in the immunoglobulin repertoire secreted by their B-1 cells. Mouse models have provided evidence that Siglec-G binds to the B cell receptor (BCR) on the B cell surface via interaction with sialic acid ligands. As an inhibitory receptor on B cells, Siglec-G controls B cell tolerance, and deficiency of this protein can increase the severity of autoimmune diseases. Despite its importance on B-1 cells, there is evidence that the control of B cell tolerance by Siglec-G occurs on conventional B-2 cells. © 2015 The New York Academy of Sciences. Source

Vegliante F.,Senckenberg Naturhistorische Sammlungen Dresden | Hasenfuss I.,Friedrich - Alexander - University, Erlangen - Nuremberg
Annual Review of Entomology | Year: 2012

The morphology of 21 exocrine glands and 13 supposedly exocrine structures recorded for lepidopteran larvae is reviewed. The epitracheal glands, for which a double role (exocrine and endocrine) has been demonstrated, are examined as well. Function is well known for at least 8 glands but completely unknown for 6 glands, for 10 putative glandular structures, and for the exocrine component of the epitracheal glands. Functional studies on the remaining structures are insufficient; in some cases (mandibular gland and adenosma) homologous glands may play a different role depending on the species, and only a few taxa have been examined. The secretions of 13 glandular types have been analyzed chemically. The histology of 11 glands is known at the ultrastructural level, whereas that of 6 glands and 7 putative glandular structures is completely unknown. Comparative anatomical studies of the osmeterium, adenosma, and Verson's glands may yield useful information for phylogenetic reconstructions. © 2012 by Annual Reviews. All rights reserved. Source

Zweier C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wieczorek D.,University of Duisburg - Essen
American Journal of Medical Genetics, Part C: Seminars in Medical Genetics | Year: 2014

Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation. In adolescent or older patients, this phenotype overlaps but is not identical with Borjeson-Forssman-Lehmann syndrome in males, caused by X-linked recessive mutations in PHF6. In younger girls there seems to be a striking phenotypic overlap with Coffin-Siris syndrome, which is characterized by intellectual disability, sparse hair and hypoplastic nails. This review will summarize and characterize the female phenotype caused by de novo aberrations in PHF6 and will discuss the overlapping and distinguishing features with Coffin-Siris syndrome. © 2014 Wiley Periodicals, Inc. Source

Ott C.,Friedrich - Alexander - University, Erlangen - Nuremberg
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology | Year: 2013

In the majority of hypertensive patients, no particular cause for abnormal blood pressure is evident (primary or essential hypertension). In contrast, in the minority of patients with secondary hypertension a specific underlying cause is responsible for the elevated blood pressure. The prevalence of secondary hypertension is higher in patients with resistant hypertension than in the general hypertensive population and increases with age. The list of secondary forms of hypertension is long and prevalence of the individual causes of secondary hypertension varies. Hence, this review divides them into two categories: common causes and rare causes. If appropriately diagnosed and treated, patients with a secondary form of hypertension might be cured, or at least show an improvement in their blood pressure control. Consequently, screening for secondary causes of hypertension plays an essential part in the care of patients with arterial hypertension. If the basal work-up raises the suspicion of a secondary cause of hypertension, specific diagnostic procedures become necessary, some of which can be performed by primary care physicians, while others require specialist input. Source

Clark T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Politzer P.,University of New Orleans | Murray J.S.,University of New Orleans
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2015

The Hellmann-Feynman theorem assures us that the forces felt by the nuclei in a molecule or complex are purely classically electrostatic. Nevertheless, it is often claimed (incorrectly) that electrostatic considerations are not sufficient to explain noncovalent interactions. Such assertions arise largely from neglecting the polarization that is inherently part of the electrostatic interaction, and must be taken into account. Accordingly, we now outline the requirements for a correct electrostatic treatment and discuss the difference between physical observables and quantities that arise from mathematical models. Polarization and donor-acceptor charge transfer are shown to be equivalent for weak interactions. However, polarization is a physical observable while charge transfer, in this context, is mathematical modelling. We also discuss some popular schemes for analyzing noncovalent interactions. © 2014 John Wiley & Sons, Ltd. Source

Evans M.E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Roth R.,University of Tubingen
Physical Review Letters | Year: 2014

The stratum corneum, the outer layer of mammalian skin, provides a remarkable barrier to the external environment, yet it has highly variable permeability properties where it actively mediates between inside and out. On prolonged exposure to water, swelling of the corneocytes (skin cells composed of keratin intermediate filaments) is the key process by which the stratum corneum controls permeability and mechanics. As for many biological systems with intricate function, the mesoscale geometry is optimized to provide functionality from basic physical principles. Here we show that a key mechanism of corneocyte swelling is the interplay of mesoscale geometry and thermodynamics: given helical tubes with woven geometry equivalent to the keratin intermediate filament arrangement, the balance of solvation free energy and elasticity induces swelling of the system, importantly with complete reversibility. Our result remarkably replicates macroscopic experimental data of native through to fully hydrated corneocytes. This finding not only highlights the importance of patterns and morphology in nature but also gives valuable insight into the functionality of skin. © 2014 American Physical Society. Source

Lampert A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Progress in molecular biology and translational science | Year: 2014

Ion channels are the bridge between the biochemical and electrical domains of our life. These membrane crossing proteins use the electric energy stored in transmembrane ion gradients, which are produced by biochemical activity to generate ionic currents. Each ion channel can be imagined as a small power plant similar to a hydroelectric power station, in which potential energy is converted into electric current. This current drives basically all physiological mechanisms of our body. It is clear that a functional blueprint of these amazing cellular power plants is essential for understanding the principle of all aspects of physiology, particularly neurophysiology. The golden path toward this blueprint starts with the biophysical investigation of ion channel activity and continues through detailed numerical modeling of these channels that will eventually lead to a full system-level description of cellular and organ physiology. Here, we discuss the first two stages of this process focusing on voltage-gated channels, particularly the voltage-gated sodium channel which is neurologically and pathologically important. We first detail the correlations between the known structure of the channel and its activity and describe some pathologies. We then provide a hands-on description of Markov modeling for voltage-gated channels. These two sections of the chapter highlight the dichotomy between the vast amounts of electrophysiological data available on voltage-gated channels and the relatively meager number of physiologically relevant models for these channels. © 2014 Elsevier Inc. All rights reserved. Source

Dey A.,TU Eindhoven | Bomans P.H.H.,TU Eindhoven | Muller F.A.,Friedrich - Schiller University of Jena | Will J.,Friedrich - Alexander - University, Erlangen - Nuremberg | And 3 more authors.
Nature Materials | Year: 2010

Unravelling the processes of calcium phosphate formation is important in our understanding of both bone and tooth formation, and also of pathological mineralization, for example in cardiovascular disease. Serum is a metastable solution from which calcium phosphate precipitates in the presence of calcifiable templates such as collagen, elastin and cell debris. A pathological deficiency of inhibitors leads to the uncontrolled deposition of calcium phosphate. In bone and teeth the formation of apatite crystals is preceded by an amorphous calcium phosphate (ACP) precursor phase. ACP formation is thought to proceed through prenucleation clusters stable clusters that are present in solution already before nucleation as was recently demonstrated for CaCO 3 (refs 15,16). However, the role of such nanometre-sized clusters as building blocks for ACP has been debated for many years. Here we demonstrate that the surface-induced formation of apatite from simulated body fluid starts with the aggregation of prenucleation clusters leading to the nucleation of ACP before the development of oriented apatite crystals. © 2010 Macmillan Publishers Limited. All rights reserved. Source

Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Muller C.P.,Kings College London | Schumann G.,Kings College London
Behavioral and Brain Sciences | Year: 2011

Proposing a change to the view on psychoactive drug use in non-addicts touches a sensitive issue because of its potential implications to addiction prevention, therapeutic practice, and drug policy. Commentators raised nine questions that ranged from clarifications, suggested extensions of the model to supporting data previously not regarded, to assumptions on the implications of the model. Here, we take up the suggestions of the commentators to expand the model to behavioral addictions, discuss additional instrumentalization goals, and review the evidence from laboratory animal studies on drug instrumentalization. We consider further the role of sociocultural factors and individual development in the establishment in drug instrumentalization and addiction. Finally, we clarify which implications we think this model may have. We conclude that drug instrumentalization theory can be further applied to other behaviors but will require a sensitive debate when used for drug and addiction policy that directly affects prevention and treatment. © 2011 Cambridge University Press. Source

Losel F.,University of Cambridge | Losel F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Farrington D.P.,University of Cambridge
American Journal of Preventive Medicine | Year: 2012

This article discusses conceptual issues and reviews knowledge about direct and buffering protective factors in the development of youth violence. Direct protective factors predict a low probability of violence, whereas buffering protective factors predict a low probability of violence in the presence of risk (and often interact with risk factors). Individual, family, school, peer, and neighborhood factors are reviewed. Heterogeneity of variables, measurement, contexts, study design, sample, and other characteristics limit generalizations. However, there were various evidence-based candidates for having a direct protective or buffering protective effect such as above-average intelligence, low impulsivity/easy temperament, enhanced anxiety, prosocial attitudes, high heart rate, close relationship to at least one parent, intensive parental supervision, medium SES of the family, sound academic achievement, strong school bonding, a positive school/class climate, nondeviant peers, and living in a nondeprived and nonviolent neighborhood. The probability of violence decreases as the number of protective factors increases (a dose-response relationship). Implications for future research and practice concern adequate research designs to detect nonlinear relationships; conceptually and methodologically homogeneous studies; differentiated analyses with regard to age, gender, and other characteristics; and greater integration of longitudinal correlational research with (quasi-)experimental intervention studies. © 2012 American Journal of Preventive Medicine. Source

Goldmann W.H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Progress in Molecular Biology and Translational Science | Year: 2014

It has been shown that focal adhesion proteins are crucial for the ability of cells to transmit external forces and to generate cytoskeletal tension. Force transmission over considerable distances and stress focusing at the focal adhesion sites make them prime candidates for mechanosensors. Temporal and spatial changes in the cytoskeletal protein configuration due to mechanical stimulation have been detected and characterized by a wide range of biophysical techniques, including magnetic twisting, magnetic tweezer, traction microscopy, atomic force microscopy, nanoscale particle tracking, and many more. The combination of these techniques will help to understand force transmission and structural remodeling in cells under loading conditions. Force transmission and force sensing represent basic biological processes that are crucial for a variety of higher fundamental cell functions including cell division, motility, and differentiation that have implications in medicine and biology. © 2014 Elsevier Inc. Source

Liu X.,Friedrich - Alexander - University, Erlangen - Nuremberg
International Journal of Logistics Research and Applications | Year: 2011

This paper investigates the extent to which logistics service providers (LSPs) translate their visions of competitiveness into management practices. It is based on a comparative study conducted in both China and the UK. The results demonstrate that both Chinese and UK LSPs have established various management practices conducive to achieving competitiveness. These practices are related to different business and operational activities of an LSP. The results also reveal a fairly high degree of similarity between the UK and Chinese LSPs with regard to their perspectives and management practices, despite their different business contexts and backgrounds. There are, nevertheless, several areas in which the views of UK and Chinese LSPs diverge, which are likely to reflect differences in the development (age and the maturity) of the UK and Chinese LSPs concerned. This is the first comparative study of LSPs in China and the UK, and it provides insights as to how LSP managers pursue competitiveness in either developing or developed countries through initiating successful management practices, and also suggests that it is important for LSP managers to establish a good understanding of their international counterparts in the competition, particularly in today's globalised world, in which more and more LSPs have extended their supply chain management to leverage value from a truly world marketplace. © 2011 Copyright Taylor and Francis Group, LLC. Source

Schuppert F.,Queens University of Belfast | Seidel C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Climatic Change | Year: 2015

According to the Budget Approach proposed by the German Advisory Council on Global Change (WBGU), allocating CO2 emission rights to countries on an equal per-capita basis would provide an ethically justified response to global climate change. In this paper, we will highlight four normative issues which beset the WBGU’s Budget Approach: (1) the approach’s core principle of distributive justice, the principle of equality, and its associated policy of emissions egalitarianism are much more complex than it initially appears; (2) the “official” rationale for determining the size of the budget should be modified in order to avoid implausible normative assumptions about the imposition of permissible intergenerational risks; (3) the approach heavily relies on trade-offs between justice and feasibility which should be stated more explicitly; and (4) part of the approach’s ethical appeal depends on policy instruments which are “detachable” from the approach’s core principle of distributive justice. © 2015, Springer Science+Business Media Dordrecht. Source

Awad A.,Sudan University of Science and Technology | German R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dressler F.,University of Innsbruck
IEEE Transactions on Mobile Computing | Year: 2011

We present the Virtual Cord Protocol (VCP), which exploits virtual coordinates to provide efficient and failure tolerant routing and data management in sensor networks. VCP maintains a virtual cord interconnecting all the nodes in the network and which, operating similar to a Distributed Hash Table (DHT), provides means for inserting data fragments into sensor nodes and retrieving them. Furthermore, it supports service discovery using indirections. VCP uses two mechanisms for finding paths to nodes and associated data items: First, it relies on the virtual cord that always provides a path toward the destination. Second, locally available neighborhood information is exploited for greedy routing. Our simulation results show that VCP is able to find paths close to the shortest path (achieving a stretch ratio of less than 125 percent) with very low overhead. We also extended VCP with data replication mechanisms to improve failure handling. The routing performance of VCP, which clearly outperforms other ad hoc routing protocols such as Dynamic MANET On Demand (DYMO), is similar to other virtual addressing schemes, e.g., Virtual Ring Routing (VRR). However, we improved VCP to handle frequent node failures in an optimized way. The presented results outline the capabilities of VCP to handle such cases more efficiently compared to other protocols. We also compared the capabilities to reliably store and retrieve data in the network to Geographic Hash Tables (GHTs). VCP, in the worst case, performs similar to GHTs, but outperforms this protocol in most cases, especially when complex routing is involved. © 2011 IEEE. Source

In this work, the remarkable high-temperature strength properties of monocrystalline γ′-hardened Ni-base superalloys are reviewed with the goal of understanding better the important role played by the γ/γ′ lattice misfit δ with respect to microstructural stability and high-temperature creep and fatigue resistance. In particular, attention is focussed on the phenomenon of microstructural degradation by directional coarsening in the form of γ/γ′ rafting which also occurs in turbine blades in service. The role played by the lattice misfit (which is negative for all currently used Ni-base superalloys) is elucidated with respect to its sign, magnitude and temperature dependence. Based on a detailed discussion of high-temperature deformation involving γ/γ′ rafting, it is argued that superalloys with a positive γ/γ′ lattice misfit should exhibit better high-temperature strength properties than otherwise similar superalloys with a negative misfit. In this context, the new class of γ′-hardened Co-base superalloys is of special interest. These alloys have promising high-temperature strength properties and possess a positive lattice mismatch. It is suggested that this positive mismatch is one of the beneficial factors that contribute to the promising properties of these alloys and that this aspect should be explored further. © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source

Zimprich D.,Friedrich - Alexander - University, Erlangen - Nuremberg | Allemand M.,University of Zurich | Lachman M.E.,Brandeis University
Psychological Assessment | Year: 2012

The present study addresses issues of measurement invariance and comparability of factor parameters of Big Five personality adjective items across age. Data from the Midlife in the United States (MIDUS) survey were used to investigate age-related developmental psychometrics of the MIDUS personality adjective items in 2 large cross-sectional samples (exploratory sample: N = 862; analysis sample: N = 3,000). After having established and replicated a comprehensive 5-factor structure of the measure, increasing levels of measurement invariance were tested across 10 age groups. Results indicate that the measure demonstrates strict measurement invariance in terms of number of factors and factor loadings. Also, we found that factor variances and covariances were equal across age groups. By contrast, a number of age-related factor mean differences emerged. The practical implications of these results are discussed, and future research is suggested. © 2011 American Psychological Association. Source

Schmieder R.E.,Friedrich - Alexander - University, Erlangen - Nuremberg
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology | Year: 2013

Out of the overall hypertensive population it is estimated that approximately 10% have treatment resistant hypertension (TRH). Percutaneous catheter-based transluminal renal ablation (renal denervation [RDN] by delivery of radiofrequency energy) has emerged as a new approach to achieve sustained blood pressure reduction in patients with TRH. This innovative interventional technique is now available across Europe for severe TRH for those patients in whom pharmacologic strategies and lifestyle changes have failed to control blood pressure below target (usually <140/90 mmHg). In 2012, the "ESH position paper: renal denervation - an interventional therapy of resistant hypertension" was published to facilitate a better understanding of the effectiveness, safety, limitation and unresolved issues. We have now updated this position paper since numerous studies have been published over the last year providing more data about the rationale, therapeutic efficacy and safety of RDN. In the upcoming ESH/ESC guidelines for the management of arterial hypertension, therapeutic options of treatment resistant hypertension will be addressed, but only briefly, and thus it is the focus of this paper to provide detailed and updated information on this innovative interventional technique. Source

Lutz E.,Free University of Berlin | Lutz E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Renzoni F.,University College London
Nature Physics | Year: 2013

Cold atoms in dissipative optical lattices exhibit an unusual transport behaviour that cannot be described within Boltzmann-Gibbs statistical mechanics. New theoretical tools and concepts need thus be developed to account for their observable macroscopic properties. Here we review recent progress achieved in the study of these processes. We emphasize the generality of the findings for a broad class of physical, chemical and biological systems, and discuss open questions and perspectives for future work. © 2013 Macmillan Publishers Limited. Source

Hepatocellular carcinomas (HCC) and bile duct carcinomas (BDC) have a poor prognosis since they are often detected at advanced stages and respond poorly to adjuvant therapy. Serum markers (e.g. AFP, CA19-9, etc.) can be used for early detection of these tumours but have only moderate sensitivity and specificity. The Golgi-associated protein GOLPH2 was found in the tissue and serum of patients with HCC and CCC and might be used to detect these tumours in time. The biopsy still remains the gold standard in the diagnosis of HCC and CCC. When biopsies are taken from these tumours they are often fragmented and contain reactive changes. Therefore immunohistochemical markers can aid in excluding or ascertaining malignancy. Studies have shown that the oncofetal protein "IGF-II mRNA-binding protein 3" (IMP3), the cell adhesion molecules P-cadherin and CD24, the cancer testis antigen MAGE-C2/CT-10 as well as the protein periostin can be used as tissue markers in the diagnosis of HCC and CCC. © 2011 Springer-Verlag. Source

Nickel F.T.,Friedrich - Alexander - University, Erlangen - Nuremberg
Handchirurgie, Mikrochirurgie, plastische Chirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft für Handchirurgie : Organ der Deutschsprachigen Arbeitsgemeinschaft für Mikrochirurgie der Peripheren Nerven und Gefässe : Organ der Vereinigung der Deutschen Plastischen Chirurgen | Year: 2010

Knowledge about the pathophysiology underlying the complex regional pain syndrome (CRPS) has increased over the last years. Classically, CRPS has been considered to be mainly driven by sympathetic dysfunction with sympathetically maintained pain being its major pathogenetic mechanism. Currently, the disease is understood as result of a complex interplay between altered somatosensory, motor, autonomic and inflammatory systems. Peripheral and central sensitization is a common feature in CRPS as in other neuropathic pain syndromes. One important mechanism is the sensitization of spinal dorsal horn cells via activation of postsynaptic NMDA-receptors by chronic C-fiber input. Differential activity of endogenous pain modulating systems may play a pivotal role in the development of CRPS, too. Neuronal plasticity of the somatosensory cortex accounts for central sensory signs. Also the motor system is subject to central adaptive changes in patients with CRPS. Calcitonin-gene related peptide (CGRP) and substance P mediate neurogenic inflammation. Additionally other proinflammatory cytokines involved in the inflammatory response in CRPS have been identified. In terms of the sympathetic nervous system, recent evidence rather points to a sensitization of adrenergic receptors than to increased efferent sympathetic activity. Particularly the expression of alpha (1)-adrenoceptors on nociceptive C-fibers may play a major role. These pathophysiological ideas do not exclude each other. In fact they complement one another. The variety of the involved systems may explain the versatile clinical picture of CRPS. Georg Thieme Verlag KG Stuttgart, New York. Source

Clark T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Clark T.,University of Portsmouth
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2013

σ-Holes are regions of positive molecular electrostatic potential collinear with and opposite to covalent bonds to atoms of Groups IV-VII. They are responsible for many noncovalent bonding interactions, such as halogen bonding. σ-Holes make 'negatively charged' atoms act as if they were 'positively charged'. The existence of σ-hole bonding emphasizes what has been called 'the fallacy of net atomic charges', which means that many covalently bonded atoms cannot be represented adequately by a single charge because they look negative from some directions and positive from others. Hydrogen bonding can also be regarded as a special case of σ-hole bonding, although in this case the origin of the σ-hole is rationalized differently than in the heavier elements. Phenomena such as the directionality of hydrogen bonds and 'blue-shifted' hydrogen bonds can be explained very simply using the σ-hole concept. © 2012 John Wiley & Sons, Ltd. Source

Spalding K.L.,Karolinska Institutet | Bergmann O.,Karolinska Institutet | Alkass K.,Karolinska Institutet | Bernard S.,Camille Jordan Institute | And 11 more authors.
Cell | Year: 2013

Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived 14C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function. © 2013 Elsevier Inc. Source

Svitlov S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Metrologia | Year: 2012

An absolute gravimeter is analysed as a linear time-invariant system in the frequency domain. Frequency responses of absolute gravimeters are derived analytically based on the propagation of the complex exponential signal through their linear measurement functions. Depending on the model of motion and the number of time-distance coordinates, an absolute gravimeter is considered as a second-order (three-level scheme) or third-order (multiple-level scheme) low-pass filter. It is shown that the behaviour of an atom absolute gravimeter in the frequency domain corresponds to that of the three-level corner-cube absolute gravimeter. Theoretical results are applied for evaluation of random and systematic measurement errors and optimization of an experiment. The developed theory agrees with known results of an absolute gravimeter analysis in the time and frequency domains and can be used for measurement uncertainty analyses, building of vibration-isolation systems and synthesis of digital filtering algorithms. © 2012 BIPM & IOP Publishing Ltd. Source

Systemic sclerosis is a chronic inflammatory multiorgan disease belonging to the group of collagen-vascular disorders. With a prevalence of 10/100,000 inhabitants it may be regarded a rather rare disease. Its etiology and pathogenesis have still not been elucidated in detail, especially with regard to the differential involvement of skin and the cause of the clinically heterogeneous disease courses. Various components of the vasculature, connective tissue as well as the immune system are involved in a yet unknown sequence and significance. Patients need to be cared for in an interdisciplinary fashion depending on the individual organ involvement. Apart from the skin, the heart, kidneys and lungs are mainly affected in addition to frequent gastrointestinal and musculoskeletal symptoms. Clinically two distinct subsets may be separated, acral (also termed limited) and diffuse scleroderma, which are characterized by anti-centromere and anti-Scl-70/topoisomerase-1 antibodies, respectively. Recent data demonstrate a poor prognosis even in limited disease when pulmonary arterial hypertension develops at an early stage. In diffuse disease sudden and rapid onset will result in a sclerosis of major internal organs and early death in many cases. © Blackwell Verlag GmbH, Berlin. Source

Junemann A.G.M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Ophthalmologe | Year: 2012

Pseudoexfoliation (PEX) glaucoma is the most frequent and most important type of secondary glaucoma, accounting for approximately 25% of open angle glaucoma worldwide and currently representing the most common identifiable cause of glaucoma overall. Due to high intraocular pressure levels, marked diurnal pressure fluctuations and spikes, and rapid optic nerve damage and visual field loss, PEX glaucoma represents a relatively severe and progressive type of glaucoma. Therefore, hard and fast lowering of intraocular pressure is necessary. Fixed combinations in medical therapy and early glaucoma surgery are recommended. When considering a surgical procedure (e. g. selective laser trabeculoplasty, bleb-dependent or bleb-independent surgery) the timing of cataract surgery plays a major role. Pathogenesis, clinical characteristics and therapeutic aspects of PEX glaucoma are described in the following article. © 2012 Springer-Verlag Berlin Heidelberg. Source

Mughrabi H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current Opinion in Solid State and Materials Science | Year: 2016

The aim of the present work is to assess in a formal manner "effective" values of the geometrical factor . α which takes into account the arrangement of the dislocation pattern in the classical Taylor flow-stress law. For this purpose, selected experimentally well-documented cases of unidirectional and cyclic plastic deformation were analyzed. It is shown that, in both monotonic and cyclic deformation, the . α-factor depends on the mode of deformation (single slip versus multiple slip). For examples of dominant primary slip interaction, a value . α . ≈. 0.1 is found. However, more frequently, . α . ≈. 0.3-0.4, typical of forest interaction, obtains. As deformation proceeds, the dislocation pattern frequently becomes more heterogeneous (cell formation) and approaches a state of lower energy, with increasing lattice misorientations which arise from an increasing density of geometrically necessary dislocations (GNDs). In these cases, . α is generally lowered, for example from an initial value of 0.35 down to values around 0.2. This behaviour is explicable in terms of the composite model in which the heterogeneity is explicitly taken into account. Very similar developments of the dislocation arrangement, accompanied by a decrease of the . α-value, are also noted during so-called "steady-state" cyclic and high-temperature creep deformations. In both cases, deformation is shown to be only quasi-stationary due to the fact that well-documented small but non-negligible microstructural changes, associated with a mild increase of the density of the GNDs, persist during deformation. The overall behaviour is readily described in an empirical manner in a unified picture. From the results obtained follows the requirement for a more general flow-stress model which considers explicitly the interaction of different slip systems and the heterogeneity of the dislocation pattern. © 2016 Elsevier Ltd. Source

Aiello A.,Max Planck Institute for the Science of Light | Aiello A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Woerdman J.P.,Leiden University
Optics Letters | Year: 2011

Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts are diffractive corrections to geometric optics that have been extensively studied for a Gaussian beam that is reflected or transmitted by a dielectric interface. Propagating in free space before and after reflection or transmission, such a Gaussian beam spreads due to diffraction. We address here the question of how the GH and IF shifts behave for a "nondiffracting" Bessel beam. © 2011 Optical Society of America. Source

Senowbari-Daryan B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Facies | Year: 2013

Tubiphytes Maslov (Nigriporella Rigby, Shamovella Rauser-Chernoussova) and similar organisms belong to one of the most abundant, enigmatic fossils reported from Carboniferous to Cretaceous rocks of numerous localities worldwide. Tubiphytes has been referred to many distinctly different organisms of the Tethys occurring in shallow water, particularly reef biotopes. Paleozoic Tubiphytes were revised by Senowbari- Daryan and Flügel, and Jurassic-Cretaceous species by Senowbari-Daryan et al. In this paper, the Triassic representatives of Tubiphytes and Tubiphytes-like organisms are described. The morphological and structural differences between the Paleozoic and Triassic Tubiphytes are shown and their systematic position is discussed. The following new species are described: Tubiphytes carnicus, T. ramosus, T. alcicornis, and Plexoramea cylindrica. The new genus Carniphytes is proposed for Tubiphytes multisiphonatus Schäfer and Senowbari-Daryan. Tubiphytes gracilis Schäfer and Senowbari-Daryan is transferred to the genus Plexoramea Mello. All described taxa are relatively abundant in Ladinian-Carnian reefs (e.g., "Wetterstein limestone" of the Alps) and in shallow-water carbonates of the northwestern Tethys. Some of them occur rarely in Anisian or in Norian-Rhaetian reefs. © Springer-Verlag Berlin Heidelberg 2012. Source

Schultheiss O.C.,Friedrich - Alexander - University, Erlangen - Nuremberg
International Journal of Psychophysiology | Year: 2013

Sugarless chewing gum is a frequently used stimulant to collect saliva samples for hormone analyses. This study tested the effect of sugarless chewing gum on cortisol, testosterone, and progesterone concentrations measured in saliva samples collected from 8 individuals at different times of the day (morning, evening) and under different collection conditions (gum, no gum) as well as in a saliva pool and water, either untreated or treated with chewing gum. Sugarless chewing gum raised all progesterone concentrations by 20 to 40. pg/mL, corresponding to a twofold increase, relative to no-gum controls and attenuated salivary testosterone and cortisol concentrations. It is recommended that the use of sugarless chewing gum as a stimulant should be avoided with saliva samples. © 2012 Elsevier B.V. Source

Eckardt K.-U.,Friedrich - Alexander - University, Erlangen - Nuremberg | Devuyst O.,University of Zurich | Johnson R.J.,University of Colorado at Denver | Kottgen A.,University Hospital Freiburg | And 2 more authors.
The Lancet | Year: 2013

Summary In the past decade, kidney disease diagnosed with objective measures of kidney damage and function has been recognised as a major public health burden. The population prevalence of chronic kidney disease exceeds 10%, and is more than 50% in high-risk subpopulations. Independent of age, sex, ethnic group, and comorbidity, strong, graded, and consistent associations exist between clinical prognosis and two hallmarks of chronic kidney disease: reduced glomerular filtration rate and increased urinary albumin excretion. Furthermore, an acute reduction in glomerular filtration rate is a risk factor for adverse clinical outcomes and the development and progression of chronic kidney disease. An increasing amount of evidence suggests that the kidneys are not only target organs of many diseases but also can strikingly aggravate or start systemic pathophysiological processes through their complex functions and effects on body homoeostasis. Risk of kidney disease has a notable genetic component, and identified genes have provided new insights into relevant abnormalities in renal structure and function and essential homoeostatic processes. Collaboration across general and specialised health-care professionals is needed to fully address the challenge of prevention of acute and chronic kidney disease and improve outcomes. © 2013 Elsevier Ltd. Source

Kriwy P.,Friedrich - Alexander - University, Erlangen - Nuremberg
International Journal of Public Health | Year: 2012

Objectives This study investigates parental decisions to vaccinate their children against measles, mumps and rubella (MMR). Parent and provider survey data allow the analysis of interactions between these major players in decision making. Methods Three datasets are used for analysis: (a) the basic population of the school entry-level health checkup in Munich, Germany; (b) a face-to-face survey with parents of children taking the school entry-level health checkup; (c) a face-to-face survey of the physicians treating these children. Logistic, OLS and multilevel regressions were applied. Results Homophily due to similar ages of parents and physicians boosts the decision to vaccinate children against MMR. Also in relation to parent-physician interaction, the fact that a physician may be homeopathic has no effect on a parents' decision to immunize, although vaccinationskeptical parents choose physicians who are trained in homeopathy. Conclusions Efforts to improve the number of parental decisions for vaccination should focus on the educational level of the parents as well as homophily of parents and physicians. Notably, homogeneity of parents and providers concerning age changes decisions in favor of vaccinating. © Swiss School of Public Health 2011. Source

Schwab S.G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wildenauer D.B.,University of Western Australia | Wildenauer D.B.,Center for Clinical Research in Neuropsychiatry
European Archives of Psychiatry and Clinical Neuroscience | Year: 2013

The influence of genetic factors in the development of schizophrenia has been convincingly demonstrated by family, twin, and adoption studies. The statistical construct of heritability is generally used for estimating the liability due to genetic factors. Heritability estimates for schizophrenia are reported to be between 60 and 80 %. Due to the technical achievements in whole genome-wide association studies, dissection of the underlying genetic factors was intensified recently, resulting in the conclusion that schizophrenia is essentially a polygenic, complex disorder. Most likely more than 100 genes, each with small effect size, contribute to disease risk. A most recent multistage genome-wide association study (Ripke et al. in Nat Genet 2013) identified 22 risk loci and estimated that 8,300 independent single-nucleotide polymorphisms contributed to the risk accounting collectively for 32 % in liability. In addition to this polygenic, complex inheritance, there is also strong indication that in some patients a deletion or insertion of a larger chromosomal region [so-called copy number variation (CNV)] might play a crucial role in pathogenesis. This could be specifically important in sporadic cases with schizophrenia, since a higher frequency of de novo mutations has been associated with these CNVs. Further studies, combining much larger sample sizes as well as application of newer technology, such as deep sequencing technologies will be necessary in order to obtain a more comprehensive understanding of the genetic foundations of schizophrenia. © Springer-Verlag Berlin Heidelberg 2013. Source

Busser C.A.,Ludwig Maximilians University of Munich | Heidrich-Meisner F.,Ludwig Maximilians University of Munich | Heidrich-Meisner F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review Letters | Year: 2013

For a double quantum dot system in a parallel geometry, we demonstrate that by combining the effects of a flux and driving an electrical current through the structure, the spin correlations between electrons localized in the dots can be controlled at will. In particular, a current can induce spin correlations even if the spins are uncorrelated in the initial equilibrium state. Therefore, we are able to engineer an entangled state in this double-dot structure. We take many-body correlations fully into account by simulating the real-time dynamics using the time-dependent density matrix renormalization group method. Using a canonical transformation, we provide an intuitive explanation for our results, related to Ruderman-Kittel-Kasuya-Yoshida physics driven by the bias. © 2013 American Physical Society. Source

Neumann H.,Friedrich - Alexander - University, Erlangen - Nuremberg | Kiesslich R.,Medical Clinic
Gastrointestinal Endoscopy Clinics of North America | Year: 2013

Two types of endomicroscopy systems exist. One is integrated into a standard, high-resolution endoscope and one is probe-based, capable of passage through the working channel of a standard endoscope. Endocytoscopy allows visualization of the superficial mucosal layer. Endoscope-integrated and probe-based devices allow magnification of the mucosa up to 1400-fold. Endomicroscopy can differentiate histologic changes of Crohn disease and ulcerative colitis in vivo in real time. Endocytoscopy can discriminate mucosal inflammatory cells, allowing determination of histopathologic activity of ulcerative colitis. Molecular imaging with fluorescence-labeled probes against disease-specific receptors will enable individualized management of inflammatory bowel diseases. © 2013 Elsevier Inc. Source

Tani F.,Max Planck Institute for the Science of Light | Travers J.C.,Max Planck Institute for the Science of Light | Russell P.S.J.,Max Planck Institute for the Science of Light | Russell P.S.J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review Letters | Year: 2013

Modulational instability (MI) of 500 fs, 5 μJ pulses, propagating in gas-filled hollow-core kagome photonic crystal fiber, is studied numerically and experimentally. By tuning the pressure and launched energy, we control the duration of the pulses emerging as a consequence of MI and hence are able to study two regimes: the classical MI case leading to few-cycle solitons of the nonlinear Schrödinger equation; and an extreme case leading to the formation of nondispersing subcycle pulses (0.5 to 2 fs) with peak intensities of order 1014 W cm-2. Insight into the two regimes is obtained using a novel statistical analysis of the soliton parameters. Numerical simulations and experimental measurements show that, when a train of these pulses is generated, strong ionization of the gas occurs. This extreme MI is used to experimentally generate a high energy (>1 μJ) and spectrally broad supercontinuum extending from the deep ultraviolet (320 nm) to the infrared (1300 nm). © 2013 American Physical Society. Source

Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Rheumatology | Year: 2014

The simultaneous presence of bone erosions and bony spurs (osteophytes, enthesophytes) in the joints of patients with psoriatic arthritis (PsA) suggests that the disease leads to enhanced bone resorption as well as increased bone formation, the latter of which has not been observed in patients with rheumatoid arthritis. At the 2013 Annual Meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members heard an update on the current research into the cytokine signature in PsA and its effects on new bone formation. Source

Schuhle D.T.,Technical University of Delft | Schuhle D.T.,Harvard University | Peters J.A.,Technical University of Delft | Schatz J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Coordination Chemistry Reviews | Year: 2011

This article exploits the special geometry of calixarene derivatives and the resulting metal binding properties with a focus on biomedical applications. The use of calixarenes as mimics of ion channels through artificial cell membranes, as mimics of metalloenzymes, and in the promising emerging field of calixarene based agents for medical imaging and radiotherapy is summarized. © 2011 Elsevier B.V. Source

Filipovic M.R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Handbook of Experimental Pharmacology | Year: 2015

The past decade has witnessed the discovery of hydrogen sulfide (H2S) as a new signalling molecule. Its ability to act as a neurotransmitter, regulator of blood pressure, immunomodulator or anti-apoptotic agent, together with its great pharmacological potential, is now well established. Notwithstanding the growing body of evidence showing the biological roles of H2S, the gap between the macroscopic descriptions and the actual mechanism(s) behind these processes is getting larger. The reactivity towards reactive oxygen and nitrogen species and/or metal centres cannot explain this plethora of biological effects. Therefore, a mechanism involving modification of protein cysteine residues to form protein persulfides is proposed. It is alternatively called S-sulfhydration. Persulfides are not particularly stable and show increased reactivity when compared to free thiols. Detection of protein persulfides is still facing methodological limitations, and mechanisms by which H2S causes this modification are still largely scarce. Persulfidation of protein such as KATP could contribute to H2S-induced vasodilation, while S-sulfhydration of GAPDH and NF-κB inhibits apoptosis. H2S regulates endoplasmic reticulum stress by causing persulfidation of PTP-1B. Several other proteins have been found to be regulated by this posttranslational modification of cysteine. This review article provides a critical overview of the current state of the literature addressing protein S-sulfhydration, with particular emphasis on the challenges and future research directions in this particular field. © Springer International Publishing Switzerland 2015. Source

Kiefer J.,University of Aberdeen | Kiefer J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Ewart P.,University of Oxford
Progress in Energy and Combustion Science | Year: 2011

Laser-based methods have transformed combustion diagnostics in the past few decades. The high intensity, coherence, high spectral resolution and frequency tunability available from laser radiation has provided powerful tools for studying microscopic processes and macroscopic phenomena in combustion by linear and non-linear optical processes. This review focuses on non-linear optical techniques based on resonant four-wave mixing for non-intrusive measurements of minor species in combustion. The importance of minor species such as reaction intermediates is outlined together with the challenges they present for detection and measurement in the hostile environments of flames, technical combustors, and engines. The limitations of conventional optical methods for such measurements are described and the particular advantages of coherent methods using non-linear optical techniques are discussed. The basic physics underlying four-wave mixing processes and theoretical models for signal calculation are then presented together with a discussion of how combustion parameters may be derived from analysis of signals generated in various four-wave mixing processes. The most important four-wave mixing processes, in this context, are then reviewed: Degenerate Four-Wave Mixing (DFWM), Coherent Anti-Stokes Raman Scattering (CARS), Laser Induced Grating Spectroscopy (LIGS) and Polarization Spectroscopy (PS). In each case the fundamental physics is outlined to explain the particular properties and diagnostic advantages of each technique. The application of the methods mentioned to molecular physics studies of combustion species is then reviewed along with their application in measurement of concentration, temperature and other combustion parameters. Related non-linear techniques and recent extensions to the ultra-fast regime are briefly reviewed. Finally practical considerations relevant to multi-dimensional and multi-species measurements, as well as applications in technical combustion systems are discussed. © 2010 Elsevier Ltd. All rights reserved. Source

Gao G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Optics express | Year: 2011

We report on photoluminescence of vanadium-doped lithium zinc silicate glasses and corresponding nanocrystalline Li2ZnSiO4 glass ceramics as broadband UV-to-VIS photoconverters. Depending on dopant concentration and synthesis conditions, VIS photoemission from [VO4]3 is centered at 550-590 nm and occurs over a bandwidth (FWHM) of ~250 nm. The corresponding excitation band covers the complete UV-B to UV-A spectral region. In as-melted glasses, the emission lifetime is about 34 μs up to a nominal dopant concentration of 0.5 mol%. In the glass ceramic, it increases to about 45 μs. For higher dopant concentration, a sharp drop in emission lifetime was observed, what is interpreted as a result of concentration quenching. Self-quenching is further promoted by energy transfer to V4+ centers (2 Source

Schramm A.M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Clowse M.E.B.,Duke University
Autoimmune Diseases | Year: 2014

Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A 2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy. © 2014 Amelie M. Schramm and Megan E. B. Clowse. Source

Ott L.,Friedrich - Alexander - University, Erlangen - Nuremberg
Microbiology (Reading, England) | Year: 2013

Corynebacterium diphtheriae, the causative agent of diphtheria, has been thoroughly studied with respect to toxin production and pili formation, while knowledge on host responses to C. diphtheriae infection is limited. In this study, we studied adhesion to and invasion of epithelial cells by different C. diphtheriae isolates. When NFκ-B reporter cell lines were used to monitor the effect of C. diphtheriae infection on human cells, strain-specific differences were observed. While adhesion to host cells had no effect, a correlation of invasion rate with NFκ-B induction was found, which indicates that internalization of bacteria is crucial for NFκ-B induction. Immunofluorescence microscopy experiments used to support the reporter assays showed that translocation of p65, as a hallmark of NFκ-B induction, was only observed in association with cell invasion by C. diphtheriae. Our data indicate that the response of epithelial cells to C. diphtheriae infection is determined by internalization of bacteria and that invasion of these cells is an active process; tetracycline-treated C. diphtheriae was still able to attach to host cells, but lost its ability to invade the cytoplasm. Recognition of pathogen-associated molecular patterns such as pili subunits by membrane-bound receptors facing the outside of the cell is not sufficient for NFκ-B induction. Source

Teich J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Proceedings of the IEEE | Year: 2012

Hardware/software codesign investigates the concurrent design of hardware and software components of complex electronic systems. It tries to exploit the synergy of hardware and software with the goal to optimize and/or satisfy design constraints such as cost, performance, and power of the final product. At the same time, it targets to reduce the time-to-market frame considerably. This paper presents major achievements of two decades of research on methods and tools for hardware/software codesign by starting with a historical survey of its roots, by highlighting its major research directions and achievements until today, and finally, by predicting in which direction research in codesign might evolve in the decades to come. © 2012 IEEE. Source

Wrede M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Regional Science | Year: 2015

Combining a spatial equilibrium model with a search-matching unemployment model, this paper analyzes the willingness to pay for regional amenities and the regional quality of life when wages, rents, and unemployment risk compensate for local amenities and disamenities. The results are compared with those obtained from the Rosen-Roback approach. We demonstrate that the traditional approach gives too much weight to the wage differential if search frictions are significant. Furthermore, the paper confirms that the wage curve is negatively sloped for quasi-linear utility. Specifically, the wage rate increases and the unemployment rate decreases in response to an increase in the amenity level if the amenity is marginally more beneficial to producers than to consumers. © 2015 Wiley Periodicals, Inc. Source

Stelzle F.,Friedrich - Alexander - University, Erlangen - Nuremberg
The International journal of oral & maxillofacial implants | Year: 2012

Piezoelectric surgery is meant to be a gentle method for implant site preparation (ISP). However, the application of load and its influence on heat development over time and effects on soft tissue are unknown. Therefore, this study sought to evaluate heat development in the bone and the duration of the procedure according to load application, as well as preservation of the sinus floor mucosa during piezoelectric ISP. One hundred twenty implant sites (6 mm deep x 3 mm wide) were prepared in the calvaria of ex vivo pig heads using piezoelectric surgery. The load applied to the working tip was increased in 100-g intervals up to 1,000 g. The bone temperature was measured, and thermal effects were analyzed histomorphometrically. The duration of each ISP was recorded. Another 12 ISPs were performed at the lateral wall of the maxillary sinus in the vicinity of the sinus floor mucosa, and sites were checked for perforation. Temperature and histologic effects of heat demonstrated a significant positive correlation with the applied load. The duration of ISP was significantly negatively correlated with load application. The maximum temperature generated by piezoelectric surgery was 64.5°C (load of 901 to 1,000 g). At a load of 401 to 500 g, the average temperature was 40.2°C ± 3.3°C, the average thermal damage extended 115.9 ± 16.3 Μm beyond the ISP area, and the maximum temperature did not exceed 47°C. The average duration of ISP using this load interval was 45.5 ± 9.4 seconds. Two perforations of the sinus floor mucosa were detected. In the present setting, the applied load during piezoelectric ISP should not exceed 500 g to prevent temperatures above 47°C in the bony implant socket. With a load of 400 to 500 g, ISP took 40 to 50 seconds. Source

Enzenhofer A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

The proposed large scale Cherenkov neutrino telescope KM3NeT will carry photo-sensors on flexible structures, the detection units. The Mediterranean Sea, where KM3NeT will be installed, constitutes a highly dynamic environment in which the detection units are constantly in motion. Thus it is necessary to monitor the exact sensor positions continuously to achieve the desired resolution for the neutrino telescope. A common way to perform this monitoring is the use of acoustic positioning systems with emitters and receivers based on the piezoelectric effect. The acoustic receivers are attached to detection units whereas the emitters are located at known positions on the sea floor. There are complete commercial systems for this application with sufficient precision. But these systems are limited in the use of their data and inefficient as they were designed to perform only this single task. Several working groups in the KM3NeT consortium are cooperating to custom-design a positioning system for the specific requirements of KM3NeT. Most of the studied solutions hold the possibility to extend the application area from positioning to additional tasks like acoustic particle detection or monitoring of the deep-sea acoustic environment. The KM3NeT Pre-Production Module (PPM) is a test system to verify the correct operation and interoperability of the major involved hardware and software components developed for KM3NeT. In the context of the PPM, alternative designs of acoustic sensors including small piezoelectric elements equipped with preamplifiers inside the same housing as the optical sensors will be tested. These will be described in this article. © 2012 Elsevier B.V. All rights reserved. Source

Redon J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Hypertension | Year: 2016

The objective is to consider the problem of high blood pressure (BP), a leading global risk factor, associated with substantial morbidity and mortality. Despite the availability of treatment guidelines and a wide range of therapies, BP control is suboptimal in many countries. Recent data indicate that only around 40% of patients manage to achieve an adequate level of BP control. A group of international experts in the field of hypertension met in 2008 to consider this problem. The resulting white paper delivered an urgent call to action and identified six key issues for improving BP control. In 2015, a working group of investigators spontaneously undertook an action with the primary aim of considering the current hypertension management situation in Europe, to discuss whether the situation had changed since 2008 and to determine what can be learnt from the projects in other continents, such as the Canadian Hypertension Education Program, which has shown that higher levels of BP control can be achieved across a general population. The working group identified the main challenges affecting the improvement of BP control today and suggests five key actions: identify the BP treatment target of less than 140/90?mmHg for the majority of patients, simplify treatment strategies and encourage pill reduction, decrease therapeutic inertia, improve patient empowerment, and involve healthcare systems and reduce the prevailing focus on drug costs in many healthcare systems. Implementing key actions identified by the working group may help to improve achievement of better BP control across Europe. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Brune K.,Friedrich - Alexander - University, Erlangen - Nuremberg | Patrignani P.,University of Chieti Pescara
Journal of Pain Research | Year: 2015

Non-steroidal anti-inflammatory drugs (NSAIDs), which act via inhibition of the cyclooxygenase (COX) isozymes, were discovered more than 100 years ago. They remain a key component of the pharmacological management of acute and chronic pain. The COX-1 and COX-2 isozymes have different biological functions; analgesic activity is primarily (although not exclusively) associated with inhibition of COX-2, while different side effects result from the inhibition of COX-1 and COX-2. All available NSAIDs, including acetaminophen and aspirin, are associated with potential side effects, particularly gastrointestinal and cardiovascular effects, related to their relative selectivity for COX-1 and COX-2. Since all NSAIDs exert their therapeutic activity through inhibition of the COX isozymes, strategies are needed to reduce the risks associated with NSAIDs while achieving sufficient pain relief. A better understanding of the inhibitory activity and COX-1/COX-2 selectivity of an NSAID at therapeutic doses, based on pharmacokinetic and pharmacodynamic properties (eg, inhibitory dose, absorption, plasma versus tissue distribution, and elimination), and the impact on drug tolerability and safety can guide the selection of appropriate NSAIDs for pain management. For example, many NSAIDs with moderate to high selectivity for COX-2 versus COX-1 can be administered at doses that maximize efficacy (∼80% inhibition of COX-2) while minimizing COX-1 inhibition and associated side effects, such as gastrointestinal toxicity. Acidic NSAIDs with favorable tissue distribution and short plasma half-lives can additionally be dosed to provide near-constant analgesia while minimizing plasma concentrations to permit recovery of COX-mediated prostaglandin production in the vascular wall and other organs. Each patient’s clinical background, including gastrointestinal and cardiovascular risk factors, should be taken into account when selecting appropriate NSAIDs. New methods are emerging to assist clinicians in the selection of appropriate NSAIDs and their doses/schedules, such as biomarkers that may predict the response to NSAID treatment in individual patients. © 2015 Brune and Patrignani. Source

Neurath M.F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Travis S.P.L.,Translational Gastroenterology Unit
Gut | Year: 2012

Recent studies have identified mucosal healing on endoscopy as a key prognostic parameter in the management of inflammatory bowel diseases (IBD), thus highlighting the role of endoscopy for monitoring of disease activity in IBD. In fact, mucosal healing has emerged as a key treatment goal in IBD that predicts sustained clinical remission and resection-free survival of patients. The structural basis of mucosal healing is an intact barrier function of the gut epithelium that prevents translocation of commensal bacteria into the mucosa and submucosa with subsequent immune cell activation. Thus, mucosal healing should be considered as an initial event in the suppression of inflammation of deeper layers of the bowel wall, rather than as a sign of complete healing of gut inflammation. In this systematic review, the clinical studies on mucosal healing are summarised and the effects of anti-inflammatory or immunosuppressive drugs such as 5-aminosalicylates, corticosteroids, azathioprine, ciclosporin and anti-TNF antibodies (adalimumab, certolizumab pegol, infliximab) on mucosal healing are discussed. Finally, the implications of mucosal healing for subsequent clinical management in patients with IBD are highlighted. Source

Avila M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Mellibovsky F.,Polytechnic University of Catalonia | Roland N.,Max Planck Institute for Dynamics and Self-Organization | Hof B.,Max Planck Institute for Dynamics and Self-Organization | Hof B.,Institute of Science and Technology Austria
Physical Review Letters | Year: 2013

Although the equations governing fluid flow are well known, there are no analytical expressions that describe the complexity of turbulent motion. A recent proposition is that in analogy to low dimensional chaotic systems, turbulence is organized around unstable solutions of the governing equations which provide the building blocks of the disordered dynamics. We report the discovery of periodic solutions which just like intermittent turbulence are spatially localized and show that turbulent transients arise from one such solution branch. © 2013 American Physical Society. Source

Mione M.,Karlsruhe Institute of Technology | Bosserhoff A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Pigment Cell and Melanoma Research | Year: 2015

Summary: The importance of microRNAs as key molecular components of cellular processes is now being recognized. Recent reports have shown that microRNAs regulate processes as diverse as protein expression and nuclear functions inside cells and are able to signal extracellularly, delivered via exosomes, to influence cell fate at a distance. The versatility of microRNAs as molecular tools inspires the design of novel strategies to control gene expression, protein stability, DNA repair and chromatin accessibility that may prove very useful for therapeutic approaches due to the extensive manageability of these small molecules. However, we still lack a comprehensive understanding of the microRNA network and its interactions with the other layers of regulatory elements in cellular and extracellular functions. This knowledge may be necessary before we exploit microRNA versatility in therapeutic settings. To identify rules of interactions between microRNAs and other regulatory systems, we begin by reviewing microRNA activities in a single cell type: the melanocyte, from development to disease. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. Source

Zahn D.,Friedrich - Alexander - University, Erlangen - Nuremberg
ChemPhysChem | Year: 2015

Recent observations of prenucleation species and multi-stage crystal nucleation processes challenge the long-established view on the thermodynamics of crystal formation. Here, we review and generalize extensions to classical nucleation theory. Going beyond the conventional implementation as has been used for more than a century now, nucleation inhibitors, precursor clusters and non-classical nucleation processes are rationalized as well by analogous concepts based on competing interface and bulk energy terms. This is illustrated by recent examples of species formed prior to/instead of crystal nucleation and multi-step nucleation processes. Much of the discussed insights were obtained from molecular simulation using advanced sampling techniques, briefly summarized herein for both nucleation-controlled and diffusion-controlled aggregate formation. © 2015 The Authors. Source

Klotz K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Metal ions in life sciences | Year: 2013

Analyses of cadmium concentrations in biological material are performed using inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), but also electrochemical methods, neutron activation analysis (NAA), and X-ray fluorescence spectrometry (XRF). The predominant sample matrices include blood, plasma, serum, and urine, as well as hair, saliva, and tissue of kidney cortex, lung, and liver. While cadmium in blood reveals rather the recent exposure situation, cadmium in urine reflects the body burden and is an indicator for the cumulative long term exposure.After chronic exposure, cadmium accumulates in the human body and causes kidney diseases, especially lesions of proximal tubular cells. A tubular proteinuria causes an increase in urinary excretion of microproteins. Excretions of retinol binding protein (RBP), β2-microglobulin (β2-M), and α1-microglobulin are validated biomarkers for analyzing cadmium effects. For this purpose, immunological procedures such as ELISA, and radio- and latex-immunoassays are used.However, proteinuria is not specific to cadmium, but can also occur after exposure to other nephrotoxic agents or due to various kidney diseases. In summary, cadmium in urine and blood are the most specific biomarkers of cadmium exposure. A combination of parameters of exposure (cadmium in blood, cadmium in urine) and parameters of effect (e.g., β2-M, RBP) is required to reveal cadmium-induced nephrological effects. Source

Anwar J.,University of Bradford | Zahn D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Angewandte Chemie - International Edition | Year: 2011

Exploring nucleation processes by molecular simulation provides a mechanistic understanding at the atomic level and also enables kinetic and thermodynamic quantities to be estimated. However, whilst the potential for modeling crystal nucleation and growth processes is immense, there are specific technical challenges to modeling. In general, rare events, such as nucleation cannot be simulated using a direct "brute force" molecular dynamics approach. The limited time and length scales that are accessible by conventional molecular dynamics simulations have inspired a number of advances to tackle problems that were considered outside the scope of molecular simulation. While general insights and features could be explored from efficient generic models, new methods paved the way to realistic crystal nucleation scenarios. The association of single ions in solvent environments, the mechanisms of motif formation, ripening reactions, and the self-organization of nanocrystals can now be investigated at the molecular level. The analysis of interactions with growth-controlling additives gives a new understanding of functionalized nanocrystals and the precipitation of composite materials. Crystal clear? New techniques of molecular simulation pave the way to explore realistic scenarios of crystal nucleation (see picture). Prospective insights into ion association, motif formation, ripening, and additive association will support experiment and, in the long run, the rational design of new materials. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Marbach H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Accounts of Chemical Research | Year: 2015

ConspectusThe investigation of porphyrin derivatives at the solid-vacuum interface has become a vivid research field with the prospect to tailor functional molecular architectures and as prototype examples to study the fundamental properties of porphyrin derivatives in regard to their vital role in many natural processes. The functional properties of the porphyrin derivatives are mainly determined by the central metal atom. Thus, the recent exploration of the surface-confined in situ metalation of porphyrins is an important step toward the realization of molecule-based functional devices. The corresponding metalation reaction of free base porphyrin derivatives can be conveniently realized in situ in ultrahigh vacuum by post- or predeposition of metal atoms or directly with substrate atoms in the so-called self-metalation. Moderate heating above room temperature (RT) might be necessary either to realize the transport of the metal to the porphyrin via diffusion or to overcome an activation barrier determined by the redox reaction itself.Surface science techniques like scanning tunneling microscopy (STM), X-ray photoelectron spectroscopy (XPS), and temperature-programmed desorption (TPD) are powerful tools to scrutinize the reaction and give valuable insights into the metalation process. For example, the completed metalation can be reflected in an enhanced apparent height of the corresponding porphyrin in STM or can be evidenced by characteristic changes in the N 1s region in XPS. These signatures allow monitoring of the progress of the metalation, and it was found that the reaction generally proceeds with very high yield.Surface diffusion of the coadsorbed metal atoms mediates the reaction and is crucial for the high yields of the corresponding reactions with pre- and postadsorbed metals. It was also demonstrated that the completed metalation can indeed significantly alter the adsorption behavior and the electronic properties and thus the functionality of the porphyrin molecules. These alterations can be used to monitor the kinetics of a particular porphyrin self-metalation reaction by STM and to estimate the activation barrier for that reaction based on isothermal measurements at different temperatures. Also TPD measurements of the H2 and D2 signals allow for the determination of corresponding activation energies for the metalation of free base porphyrins and their deuterized analogues. Gas phase DFT calculations of the metalation of the ′bare′ free base porphyrin macrocycle identify intermediate reaction steps with the transfer of the first hydrogen atom to the metal center being the main barrier to overcome. The values from these calculations are in fair agreement with experimentally determined ones. However, TPD based results indicate that exchanges of deuterium and hydrogen between the central nitrogen and the surface occur, which indicate an active role of the surface and challenge the findings from gas phase DFT.The in situ metalation of porphyrins at the solid-vacuum interface is established as a novel and convenient route to tailor functional molecular architectures. With different surface science techniques detailed insights into the surface-mediated metalation reaction were achieved for this class of prototype functional molecules. © 2015 American Chemical Society. Source

Viehmann O.,Ludwig Maximilians University of Munich | Von Delft J.,Ludwig Maximilians University of Munich | Marquardt F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review Letters | Year: 2013

We show how a quantum Ising spin chain in a time-dependent transverse magnetic field can be simulated and experimentally probed in the framework of circuit QED with current technology. The proposed setup provides a new platform for observing the nonequilibrium dynamics of interacting many-body systems. We calculate its spectrum to offer a guideline for its initial experimental characterization. We demonstrate that quench dynamics and the propagation of localized excitations can be observed with the proposed setup and discuss further possible applications and modifications of this circuit QED quantum simulator. © 2013 American Physical Society. Source

Backert S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hofreuter D.,Hannover Medical School
Journal of Microbiological Methods | Year: 2013

Campylobacter jejuni is a spiral-shaped Gram-negative pathogen and major agent of gastrointestinal foodborne illness in humans worldwide. This pathogen encodes numerous described pathogenicity-associated factors involved in important processes including bacterial adhesion to, transmigration across, invasion into and intracellular survival within intestinal epithelial cells. This review article highlights various molecular techniques applied in the studies of each of these individual steps of C. jejuni host cell interactions in vitro including gentamicin protection assay, chemotaxis and motility assays, transwell and intracellular survival assays, G-Lisa, siRNA knockdown, immunohistochemistry, immunofluorescence, electron microscopy and luciferase reporter assays. We discuss the strengths and limitations of the methods as well as the different cell model systems applied. Future work should employ new technologies including modern microscopic, proteomics-based and cell signaling approaches to identify and characterise novel virulence mechanisms, which are crucial to provide fresh insights into the diversity of strategies employed by this important pathogen to cause disease. © 2013 The Authors. Source

Bogdan C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Trends in Immunology | Year: 2015

Thirty years after the discovery of its production by activated macrophages, our appreciation of the diverse roles of nitric oxide (NO) continues to grow. Recent findings have not only expanded our understanding of the mechanisms controlling the expression of NO synthases (NOS) in innate and adaptive immune cells, but have also revealed new functions and modes of action of NO in the control and escape of infectious pathogens, in T and B cell differentiation, and in tumor defense. I discuss these findings, in the context of a comprehensive overview of the various sources and multiple reaction partners of NO, and of the regulation of NOS2 by micromilieu factors, antisense RNAs, and 'unexpected' cytokines. © 2015 Elsevier Ltd. Source

Davranche A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Lefebvre G.,Tour du Valat Research Center | Poulin B.,Tour du Valat Research Center
Remote Sensing of Environment | Year: 2010

Multiseason reflectance data from radiometrically and geometrically corrected multispectral SPOT-5 images of 10-m resolution were combined with thorough field campaigns and land cover digitizing using a binary classification tree algorithm to estimate the area of marshes covered with common reeds (Phragmites australis) and submerged macrophytes (Potamogeton pectinatus, P. pusillus, Myriophyllum spicatum, Ruppia maritima, Chara sp.) over an area of 145,000 ha. Accuracy of these models was estimated by cross-validation and by calculating the percentage of correctly classified pixels on the resulting maps. Robustness of this approach was assessed by applying these models to an independent set of images using independent field data for validation. Biophysical parameters of both habitat types were used to interpret the misclassifications. The resulting trees provided a cross-validation accuracy of 98.7% for common reed and 97.4% for submerged macrophytes. Variables discriminating reed marshes from other land covers were the difference in the near-infrared band between March and June, the Optimized Soil Adjusted Vegetation Index of December, and the Normalized Difference Water Index (NDWI) of September. Submerged macrophyte beds were discriminated with the shortwave-infrared band of December, the NDWI of September, the red band of September and the Simple Ratio index of March. Mapping validations provided accuracies of 98.6% (2005) and 98.1% (2006) for common reed, and 86.7% (2005) and 85.9% (2006) for submerged macrophytes. The combination of multispectral and multiseasonal satellite data thus discriminated these wetland vegetation types efficiently. Misclassifications were partly explained by digitizing inaccuracies, and were not related to biophysical parameters for reedbeds. The classification accuracy of submerged macrophytes was influenced by the proportion of plants showing on the water surface, percent cover of submerged species, water turbidity, and salinity. Classification trees applied to time series of SPOT-5 images appear as a powerful and reliable tool for monitoring wetland vegetation experiencing different hydrological regimes even with a small training sample (N = 25) when initially combined with thorough field measurements. © 2009 Elsevier Inc. All rights reserved. Source

Zahn D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Chemical Physics Letters | Year: 2013

The atomistic mechanism of the perovskite → post-perovskite transformation of MgSiO3 is explored from molecular simulation mimicking extreme pressure and temperature conditions akin to planet Earth's interior (D″ region). The nucleation process is highly anisotropic and initiated by column-wise rotation of SiO6 octahedra around the [0 0 1] direction. The post-perovskite transition is found to be a rare event (i.e. one requiring substantial activation energy, ∼15 eV for the critical nucleus, but, once started, propagates very fast (103-104 m/s). The most stable phase front, the (0 1 0) interface, propagates at only 10% of the speed of the (0 0 1) phase front. © 2013 Elsevier B.V. All rights reserved. Source

Quick H.H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Magnetic Resonance Imaging | Year: 2014

Integrated whole-body PET/MR hybrid imaging combines excellent soft tissue contrast and various functional imaging parameters provided by MR with high sensitivity and quantification of radiotracer metabolism provided by positron emission tomography (PET). While clinical evaluation now is under way, integrated PET/MR demands for new technologies and innovative solutions, currently subject to interdisciplinary research. Attenuation correction of human soft tissues and of hardware components has to be MR-based to maintain quantification of PET imaging because computed tomography (CT) attenuation information is missing. This brings up the question of how to provide bone information with MR imaging. The limited field-of-view in MR imaging leads to truncations in body imaging and MR-based attenuation correction. Another research field is the implementation of motion correction technologies to correct for breathing and cardiac motion in view of the relatively long PET data acquisition times. Initial clinical applications of integrated PET/MR in oncology, neurology, pediatric oncology, and cardiovascular disease are highlighted. The hybrid imaging workflow here has to be tailored to the clinical indication to maximize diagnostic information while minimizing acquisition time. PET/MR introduces new artifacts that need special observation and innovative solutions for correction. Finally, the rising need for appropriate phantoms and standardization efforts in PET/MR hybrid imaging is discussed. Copyright © 2013 Wiley Periodicals, Inc. Source

Beier J.P.,Friedrich - Alexander - University, Erlangen - Nuremberg
Cell biology international | Year: 2011

TE (tissue engineering) of skeletal muscle is a promising method to reconstruct loss of muscle tissue. This study evaluates MSCs (mesenchymal stem cells) as new cell source for this application. As a new approach to differentiate the MSCs towards the myogenic lineage, co-cultivation with primary myoblasts has been developed and the myogenic potential of GFP (green fluorescent protein)-transduced rat MSC co-cultured with primary rat myoblasts was assessed by ICC (immunocytochemistry). Myogenic potential of MSC was analysed by ICC, FACS and qPCR (quantitative PCR). MSC-myoblast fusion phenomena leading to hybrid myotubes were evaluated using a novel method to evaluate myotube fusion ratios based on phase contrast and fluorescence microscopy. Furthermore, MSC constitutively expressed the myogenic markers MEF2 (myogenic enhancer factor 2) and α-sarcomeric actin, and MEF2 expression was up-regulated upon co-cultivation with primary myoblasts and the addition of myogenic medium supplements. Significantly higher numbers of MSC nuclei were involved in myotube formations when bFGF (basic fibroblast growth factor) and dexamethasone were added to co-cultures. In summary, we have determined optimal co-culture conditions for MSC myogenic differentiation up to myotube formations as a promising step towards applicability of MSC as a cell source for skeletal muscle TE as well as other muscle cell-based therapies. Source

Zahn D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Molecular Modeling | Year: 2011

Concepts of modeling ion conductors by means of molecular dynamics simulations are outlined and exemplified by a small series of applications. Computational studies offer atomic level of detail insights into ionic mobility and thus help to rationalize experimental findings in particular for complex ion conduction mechanisms. Standard techniques are discussed within their thermodynamic context, i.e., chemical potentials, conductivity and activation energies. The limitations of molecular dynamics simulations are defined by statistics and the accuracy in evaluating atomic interactions. © 2010 Springer-Verlag. Source

Brabec C.J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Heeney M.,Imperial College London | McCulloch I.,Imperial College London | Nelson J.,Imperial College London
Chemical Society Reviews | Year: 2011

The performance of organic photovoltaic devices based upon bulk heterojunction blends of donor and acceptor materials has been shown to be highly dependent on the thin film microstructure. In this tutorial review, we discuss the factors responsible for influencing blend microstructure and how these affect device performance. In particular we discuss how various molecular design approaches can affect the thin film morphology of both the donor and acceptor components, as well as their blend microstructure. We further examine the influence of polymer molecular weight and blend composition upon device performance, and discuss how a variety of processing techniques can be used to control the blend microstructure, leading to improvements in solar cell efficiencies. © 2011 The Royal Society of Chemistry. Source

Volkert D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Aktuelle Ernahrungsmedizin | Year: 2011

Several age-related changes, in particular with respect to the regulation of food and fluid intake and body composition, but also regarding health and living situation, increase the risk of malnutrition and dehydration in elderly people. Particularly in combination with illness and functional impairments malnutrition is frequent. In most cases the origin of malnutrition is multifactorial. Since it is more difficult in older compared to younger adults to regain lost body weight, preventive approaches gain in importance. Screening of malnutrition should be performed routinely and be part of all medical consultations of older persons, in order to recognize nutritional problems as early as possible. Nutritional therapy should be individualized, eliminate existing causes of malnutrition and accomplished in a multidisciplinary team. Generally, all options of nutritional therapy can be considered in the elderly from dietetic measures to oral nutritional supplements, enteral and parenteral feeding. © 2011 Georg Thieme Verlag KG Stuttgart · New York. Source

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. Source

The present article reports on a long-term study in the course of which individuals who had studied mathematics finishing with either a state exam or a diploma were interviewed at the end of their studies and again ten years after they had started working in their professional field. The aim was to examine how far socio-cognitive variables (professional self-efficiency, professional aims) and self-concept (operative and communal component) allow predicting professional success ten years later. In this, objective professional success is measured by the amount and scope of work, whereas subjective professional success is measured on the basis of a subjective assessment of achievement as well as the degree of satisfaction with the job and the feeling of stress (both in general and specifically in relation with the job of a teacher). Findings show that, at the end of their studies, those individuals finishing with a state exam differed from those taking a diploma with regard to both their aims and their self-concepts. Ten years after having finished their studies, the percentage of working mothers among the maths teachers is smaller than that of employed women with children among mathematicians with a diploma. Teachers feel in general more stressed and are less satisfied with their job than the group of individuals with a diploma. Self-efficiency and an operative self-concept have an impact on both the employment and the satisfaction with one's work as well as on the achievement assessment and (in reverse) on the feeling of stress. Compatibility-related aims have a negative influence on the satisfaction with the job. Consequences for possible measures to be taken in teacher training are discussed. Source

Holzer S.U.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hensel M.,University of Osnabruck
PLoS ONE | Year: 2012

The molecular mechanisms of virulence of the gastrointestinal pathogen Salmonella enterica are commonly studied using cell culture models of infection. In this work, we performed a direct comparison of the interaction of S. enterica serovar Typhimurium (S. Typhimurium) with the non-polarized epithelial cell line HeLa, the polarized cell lines CaCo2, T84 and MDCK, and macrophage-like RAW264.7 cells. The ability of S. Typhimurium wild-type and previously characterized auxotrophic mutant strains to enter host cells, survive and proliferate within mammalian cells and deploy the Salmonella Pathogenicity Island 2-encoded type III secretion system (SPI2-T3SS) was quantified. We found that the entry of S. Typhimurium into polarized cells was much more efficient than entry into non-polarized cells or phagocytic uptake. While SPI2-T3SS dependent intracellular proliferation was observed in HeLa and RAW cells, the intracellular replication in polarized cells was highly restricted and not affected by defective SPI2-T3SS. The contribution of aromatic amino acid metabolism and purine biosynthesis to intracellular proliferation was distinct in the various cell lines investigated. These observations indicate that the virulence phenotypes of S. Typhimurium are significantly affected by the cell culture model applied. © 2012 Hölzer, Hensel. Source

Nimmerjahn F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Ravetch J.V.,Rockefeller University
Current Topics in Microbiology and Immunology | Year: 2010

Genetic defects affecting the humoral immune response and especially the production of antibodies of the immunoglobulin G (IgG) isotype result in a heightened susceptibility to infections. Studies over the last years have demonstrated the crucial role of Fc-receptors for IgG (FcγRs) widely expressed on innate immune effector cells in mediating the protective function of IgG. During the last years, additional ligands interacting with FcγRs as well as additional receptors binding to IgG glycosylation variants have been identified. In this review, we discuss how the interaction of these different ligands with classical and novel Fcγ-receptors influences the immune response and which strategies microorganisms have developed to prevent them. © Springer-Verlag Berlin Heidelberg 2011. Source

Emmert M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Gesundheitswesen (Bundesverband der Ärzte des Öffentlichen Gesundheitsdienstes (Germany)) | Year: 2012

Public reporting (PR) has been gaining more weight as a mechanism for patient steerage. According to the theory of PR, patients use information about the quality of health care providers before making decisions and selecting health-care providers. This paper contributes further knowledge on the effectiveness of PR and identifies critical success factors. These should be taken into account when implementing PR in the German health care system. The peer-reviewed English, Spanish, and German language literature was searched in the following five databases: The Cochrane Library, Medline (via PubMed), ISI Web of Knowledge, EconLit, and PsycINFO (since 2005). In addition, reference lists of the included studies and reviews were screened in order to identify previously published studies. In total, 21 studies were identified regarding the impact of 12 different PR instruments on patient steerage. An impact could be demonstrated in 9 studies, 7 studies showed mixed results, while 5 studies could not show any effect on patient steerage. 20 studies were carried out in the US environment, 1 study in Germany. The most researched instrument is the New York State Cardiac Surgery Reporting System (N=8). PR can be effective in steering patients when seeking a health-care provider, especially for elective procedures. To be successful, information provided must be reliable, easily understandable, should further represent real news, and be disseminated widely. Besides this, it has to be applicable and modifiable according to individual preferences. © Georg Thieme Verlag KG Stuttgart · New York. Source

Schulte P.,Friedrich - Alexander - University, Erlangen - Nuremberg
Philosophia (United States) | Year: 2012

How do frogs represent their prey? This question has been the focus of many debates among proponents of naturalistic theories of content, especially among proponents of teleosemantics. This is because alternative versions of the teleosemantic approach have different implications for the content of frog representations, and it is still controversial which of these content ascriptions (if any) is the most adequate. Theorists often appeal to intuitions here, but this is a dubious strategy. In this paper, I suggest an alternative, empirical test for theories of content. I propose that we should examine whether a theory generates content ascriptions that fit with our best scientific explanations of animal behavior. I then focus on the most prominent version of teleosemantics, Ruth Millikan's consumer-oriented approach, and argue that it fails the empirical test in the frog case, since it yields a content ascription that (i) does not include properties that should be included (namely, being small, dark and moving) and (ii) includes a property that should not be included (namely, being frog food). This is an important result in itself, but it also demonstrates by way of example how progress can be made in the complex debate about theories of content. © 2012 Springer Science+Business Media B.V. Source

Riehle D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Information Systems and e-Business Management | Year: 2012

Single-vendor commercial open source software projects are open source software projects that are owned by a single firm that derives a direct and significant revenue stream from the software. Single-vendor commercial open source at first glance represents an economic paradox: How can a firm earn money if it is making its product available for free as open source? This paper presents the core properties of single-vendor open source business models and discusses how they work. Using a single-vendor open source approach, firms can get to market faster with a superior product at lower cost than possible for traditional competitors. The paper shows how these benefits accrue from an engaged and self-supporting user community. Lacking any prior comprehensive reference, this paper is based on an analysis of public statements by practitioners of single-vendor open source. It forges the various anecdotes into a coherent description of revenue generation strategies and relevant business functions. © 2010 Springer-Verlag. Source

Schnabel J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment | Year: 2013

The energy reconstruction of both neutrino-induced muons from neutrino interactions in the vicinity of the detector and of muons from cosmic ray air showers contributes indispensable information for a broad range of physics analyses, e.g. by increasing the sensitivity in neutrino point source searches or in offering access to observables such as the atmospheric neutrino spectrum. Currently, four energy reconstruction methods are implemented in the ANTARES data analysis framework, ranging from estimates based on photon counting and the total charge deposited in the detector to methods based on probability density functions and Artificial Neural Networks. These four methods, their performance and systematic studies of the energy resolution capabilities of the ANTARES detector are presented. © 2012 Elsevier B.V. All rights reserved. Source

Bibi F.,Leibniz Institute for Evolution and Biodiversity Science | Kiessling W.,Leibniz Institute for Evolution and Biodiversity Science | Kiessling W.,Friedrich - Alexander - University, Erlangen - Nuremberg
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

Much debate has revolved around the question of whether the mode of evolutionary and ecological turnover in the fossil record of African mammals was continuous or pulsed, and the degree to which faunal turnover tracked changes in global climate. Here, we assembled and analyzed large specimen databases of the fossil record of eastern African Bovidae (antelopes) and Turkana Basin large mammals. Our results indicate that speciation and extinction proceeded continuously throughout the Pliocene and Pleistocene, as did increases in the relative abundance of arid-adapted bovids, and in bovid body mass. Species durations were similar among clades with different ecological attributes. Occupancy patterns were unimodal, with long and nearly symmetrical origination and extinction phases. A single origination pulse may be present at 2.01.75 Ma, but besides this, there is no evidence that evolutionary or ecological changes in the eastern African record tracked rapid, 100,000-y-scale changes in global climate. Rather, eastern African large mammal evolution tracked global or regional climatic trends at long (million year) time scales, while local, basin-scale changes (e.g., tectonic or hydrographic) and biotic interactions ruled at shorter timescales. Source

Reinhard P.-G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Suraud E.,Toulouse 1 University Capitole
Annals of Physics | Year: 2015

We propose a relaxation time approximation for the description of the dynamics of strongly excited fermion systems. Our approach is based on time-dependent density functional theory at the level of the local density approximation. This mean-field picture is augmented by collisional correlations handled in relaxation time approximation which is inspired from the corresponding semi-classical picture. The method involves the estimate of microscopic relaxation rates/times which is presently taken from the well established semi-classical experience. The relaxation time approximation implies evaluation of the instantaneous equilibrium state towards which the dynamical state is progressively driven at the pace of the microscopic relaxation time. As test case, we consider Na clusters of various sizes excited either by a swift ion projectile or by a short and intense laser pulse, driven in various dynamical regimes ranging from linear to strongly non-linear reactions. We observe a strong effect of dissipation on sensitive observables such as net ionization and angular distributions of emitted electrons. The effect is especially large for moderate excitations where typical relaxation/dissipation time scales efficiently compete with ionization for dissipating the available excitation energy. Technical details on the actual procedure to implement a working recipe of such a quantum relaxation approximation are given in appendices for completeness. © 2014 Elsevier Inc. Source

Mardin C.Y.,Friedrich - Alexander - University, Erlangen - Nuremberg
Klinische Monatsblatter fur Augenheilkunde | Year: 2012

Glaucomatous optic atrophy is the result of both primary and secondary glaucomas leading to functional defects. Loss of axons and ganglion cells leads to a specific atrophy of the optic nerve head. Increased cup size and depth with loss of neuroretinal rim tissue are accompanied by changes of the retinal vessels and juxtapapillary retinal pigment epithelium. Changes of the retinal nerve fibre layer, caused by ganglion cell loss may be earliest signs of glaucomatous atrophy. The marked variability of optic disc size and form may influence the quality of ophthalmoscopic evaluation in extreme variants. Peripapillary haemorrhages and changes of pulsation properties of the retinal venules may give prognostic information for the course of the disease. These signs may be evaluated and even semiquantitatively measured with limited technical effort. They lay the basis for the evaluation of modern imaging and measuring techniques. This article summarises criteria described by Jonas and other authors in the light of modern imaging techniques and adds the latest scientific results. © Georg Thieme Verlag KG · Stuttgart · New York. Source

Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Rudwaleit M.,Franklin University
Best Practice and Research: Clinical Rheumatology | Year: 2010

Ankylosing spondylitis is characterised by inflammation of the spine and the entheses followed by bone formation. Excessive bone formation in ankylosing spondylitis leads to the formation of bone spurs, such as syndesmophytes and enthesiophytes, which contribute to ankylosis of joints and poor physical function. This process is based on increased differentiation of osteoblasts from their mesenchymal precursors, which allows to rapidly build up new bone. Prostaglandins, bone morphogenic proteins and Wnt proteins play an essential role in this process. By contrast, tumour necrosis factor (TNF) does not appear to be the direct trigger for osteophyte formation in ankylosing spondylitis. The article reviews the current knowledge regarding the mechanisms and clinical role of ankylosis and explains strategies on how to prevent it in patients with ankylosing spondylitis. © 2009 Elsevier Ltd. All rights reserved. Source

De Nittis G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Gomi K.,Shinshu University
Communications in Mathematical Physics | Year: 2015

We provide a classification of type AII topological quantum systems in dimension d = 1, 2, 3, 4. Our analysis is based on the construction of a topological invariant, the FKMM-invariant, which completely classifies “Quaternionic” vector bundles (a.k.a. “symplectic” vector bundles) in dimension d ≤ 3. This invariant takes value in a proper equivariant cohomology theory and, in the case of examples of physical interest, it reproduces the familiar Fu-Kane-Mele index. In the case d = 4 the classification requires a combined use of the FKMM-invariant and the second Chern class. Among the other things, we prove that the FKMM-invariant is a bona fide characteristic class for the category of “Quaternionic” vector bundles in the sense that it can be realized as the pullback of a universal topological invariant. © Springer-Verlag Berlin Heidelberg 2015. Source

Riehle D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Computer | Year: 2010

By establishing a successful open source platform, software firms can compete more effectively across technology stacks and thereby increase their addressable market. © 2006 IEEE. Source

Naumann I.,Friedrich - Alexander - University, Erlangen - Nuremberg
Rapid communications in mass spectrometry : RCM | Year: 2011

The pharmaceutical industry is interested in identifying novel target compounds. Due to their versatile pharmacological activities (e.g. antiviral, anti-carcinogen and immunosuppressive) sulfoquinovosyldiacylglycerides (SQDGs) are potential drug candidates. The present publication deals with the purification and structural characterization of SQDGs from three different strains of Phaeodactylum tricornutum. Besides detection of SQDGs (sn-1: C16:1/sn-2: C16:0 and sn-1: C20:5/sn-2: C16:0), two novel 2'-O-acylsulfoquinovosyldiacylglyerides (Ac-SQDGs, sn-1: C16:0/ sn-2: C16:0/2' C20:5 and sn-1: C20:5/sn-2: C16:0/2' C20:5) were identified by using matrix-assisted laser desorption/ionization (MALDI) QTrap time-of-flight (ToF) hybrid mass spectrometry (MS) with multistage MS(n). The analytical method enables the sn-position verification of fatty acids (MS(2)) as well as the confirmation of the regioposition of eicospentanoic acid at the sulfoquinovose (MS(3)). Copyright © 2011 John Wiley & Sons, Ltd. Source

Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg
European Journal of Clinical Investigation | Year: 2011

Background Inflammatory diseases are linked to enhanced bone loss. The effect of inflammation on bone is mediated by proinflammatory cytokines, which regulate bone formation as well as bone resorption thereby altering bone homeostasis. Materials and methods In this article we summarize the key insights in cytokine regulation of bone. We describe the major pro- and anti-inflammatory mediators, which are involved in the regulation of bone and describe the mechanisms by which these cytokines alter bone balance. Results We describe the effects of tumor necrosis factor (TNF), interleukin (IL)- 1 family members, IL-6, IL-17 and interferons (IFN) on bone and discuss the mechanisms by which these individual cytokines affect the bone resorbing and the bone forming cells. Conclusions Several proinflammatory cytokines (such as TNFa, IL-1 and IL-17) are major triggers for osteoclast activation explaining the enhanced bone loss during inflammation. Other such as IL-12, IL-18, IL-33 and IFN are strong suppressors of osteoclast differentiation and inhibit bone loss. Thus the cytokine composition of an inflammatory tissue is decisive whether inflammation triggers bone loss or not. © 2011 The Author. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation. Source

Dressler F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Akan O.B.,Middle East Technical University
Computer Networks | Year: 2010

The developments in the communication and networking technologies have yielded many existing and envisioned information network architectures such as cognitive radio networks, sensor and actor networks, quantum communication networks, terrestrial next generation Internet, and InterPlaNetary Internet. However, there exist many common significant challenges to be addressed for the practical realization of these current and envisioned networking paradigms such as the increased complexity with large scale networks, their dynamic nature, resource constraints, heterogeneous architectures, absence or impracticality of centralized control and infrastructure, need for survivability, and unattended resolution of potential failures. These challenges have been successfully dealt with by Nature, which, as a result of millions of years of evolution, have yielded many biological systems and processes with intrinsic appealing characteristics such as adaptivity to varying environmental conditions, inherent resiliency to failures and damages, successful and collaborative operation on the basis of a limited set of rules and with global intelligence which is larger than superposition of individuals, self-organization, survivability, and evolvability. Inspired by these characteristics, many researchers are currently engaged in developing innovative design paradigms to address the networking challenges of existing and envisioned information systems. In this paper, the current state-of-the-art in bio-inspired networking is captured. The existing bio-inspired networking and communication protocols and algorithms devised by looking at biology as a source of inspiration, and by mimicking the laws and dynamics governing these systems are presented along with open research issues for the bio-inspired networking. Furthermore, the domain of bio-inspired networking is linked to the emerging research domain of nanonetworks, which bring a set of unique challenges. The objective of this survey is to provide better understanding of the potentials for bio-inspired networking which is currently far from being fully recognized, and to motivate the research community to further explore this timely and exciting topic. © 2010 Elsevier B.V. All rights reserved. Source

Achenbach S.,Friedrich - Alexander - University, Erlangen - Nuremberg
JACC. Cardiovascular imaging | Year: 2010

Imaging plays a central role in the diagnosis and management of coronary artery disease. Imaging is used for the detection of underlying coronary artery stenoses in patients with stable or chronic chest pain, for the assessment of myocardial scar and viability, for assessing prognosis, or for predicting complications. Echocardiography, nuclear imaging, cardiac magnetic resonance, and-more recently-computed tomography are powerful tools to provide answers to these questions. New technology, new contrast agents, and newly developed imaging protocols widen the applicability and increase accuracy of these imaging modalities, and new clinical studies provide information on their diagnostic potential and their therapeutic as well as prognostic value. The relative strengths and weaknesses of the different imaging modalities influence the selection of the most appropriate imaging approach in different clinical scenarios. This article outlines some of the most important developments of the past 12 months in the field of echocardiography, nuclear imaging, cardiac magnetic resonance, and computed tomography as they pertain to coronary artery disease. Copyright © 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. Source

Papastavrou A.,Hochschule fur Angewandte Wissenschaften Ingolstadt | Steinmann P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Kuhl E.,Stanford University
Journal of the Mechanics and Physics of Solids | Year: 2013

Many biological systems are coated by thin films for protection, selective absorption, or transmembrane transport. A typical example is the mucous membrane covering the airways, the esophagus, and the intestine. Biological surfaces typically display a distinct mechanical behavior from the bulk; in particular, they may grow at different rates. Growth, morphological instabilities, and buckling of biological surfaces have been studied intensely by approximating the surface as a layer of finite thickness; however, growth has never been attributed to the surface itself. Here, we establish a theory of continua with boundary energies and growing surfaces of zero thickness in which the surface is equipped with its own potential energy and is allowed to grow independently of the bulk. In complete analogy to the kinematic equations, the balance equations, and the constitutive equations of a growing solid body, we derive the governing equations for a growing surface. We illustrate their spatial discretization using the finite element method, and discuss their consistent algorithmic linearization. To demonstrate the conceptual differences between volume and surface growth, we simulate the constrained growth of the inner layer of a cylindrical tube. Our novel approach toward continua with growing surfaces is capable of predicting extreme growth of the inner cylindrical surface, which more than doubles its initial area. The underlying algorithmic framework is robust and stable; it allows to predict morphological changes due to surface growth during the onset of buckling and beyond. The modeling of surface growth has immediate biomedical applications in the diagnosis and treatment of asthma, gastritis, obstructive sleep apnoea, and tumor invasion. Beyond biomedical applications, the scientific understanding of growth-induced morphological instabilities and surface wrinkling has important implications in material sciences, manufacturing, and microfabrication, with applications in soft lithography, metrology, and flexible electronics. © 2013 Elsevier Ltd. Source

Huntley J.W.,Friedrich - Alexander - University, Erlangen - Nuremberg | Scarponi D.,University of Bologna
Paleobiology | Year: 2012

The role of antagonistic organismal interactions in the production of long-term macroevolutionary trends has been debated for decades. Some evidence seems to suggest that temporal trends in predation frequency share a common causative mechanism with genus-level diversity, whereas studies on the role of parasites in "shaping" the evolutionary process are rare indeed. Digenean trematodes (Phylum Platyhelminthes) infest molluscs in at least one stage of their complex life cycle. Trematodes leave characteristic oval-shaped pits with raised rims on the interior of their bivalve hosts, and these pits are preserved in the fossil record. Here we survey 11,785 valves from the PleistoceneHolocene deposits of the Po Plain and from nearby modern coastal environments on the northeast Adriatic coast of Italy. Of these, 205 valves exhibited trematode-induced pits. Trematodes were selective parasites in terms of host taxonomy and host body size. Infestation was restricted to lower shoreface/transition-to-platform paleoenvironments. During the Holocene, individuals from the transgressive systems tract were significantly more likely to be infested than those from highstand systems tracts. Temporal trends in infestation frequency cannot be explained as an ecological/evolutionary phenomenon (e.g., the hypothesis of escalation); instead the trend seems controlled by environmental variation induced by glacio-eustatic sea-level changes and inadequate sampling. Because this interaction appears to be ephemeral, both temporally and spatially, it is not likely that any selective pressure would be continuous over geologic time in this region. Furthermore, these results support the hypothesis that antagonistic interactions are lower in the northern Adriatic Sea in comparison to other midlatitude shallow marine settings. © 2012 The Paleontological Society. Source

Jung D.,University of Augsburg | Hartmann M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Catalysis Today | Year: 2010

Green chemistry and environmentally benign reaction engineering play an important role for future industrial processes. It is expected that the number of chemical reactions carried out via enzymatic catalysis will increase strongly. To achieve this aim, stable (viz. leaching and deactivation is prevented) heterogeneous biocatalysts are required. In this study, cross-linked enzyme aggregates of chloroperoxidase were grown in large-pore mesocellular foams (MCF). By changing the various synthesis parameters, the specific activity and the effective activity (viz. the enzyme activity units per mmol of adsorbed enzyme) are improved. The resulting biocatalysts composed of cross-linked chloroperoxidase and cross-linked glucose oxidase were tested in the oxidation of indole. The catalytic test under continuous operation conditions in a fixed-bed reactor confirmed that the cross-linked enzymes are less prone to leaching compared to the physically adsorbed enzymes in the pores of MCF or SBA-15. © 2010 Elsevier B.V. All rights reserved. Source

Agaimy A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Advances in Anatomic Pathology | Year: 2014

Since the description of atypical teratoid/rhabdoid tumors of the central nervous system and renal/extrarenal malignant rhabdoid tumors in children, the clinicopathologic spectrum of neoplasms having in common a highly variable rhabdoid cell component (0% to 100%) and consistent loss of nuclear SMARCB1 (INI1) expression has been steadily expanding to include cribriform neuroepithelial tumor of the ventricle, renal medullary carcinoma and a subset of collecting duct carcinoma, epithelioid sarcoma, subsets of miscellaneous benign and malignant soft tissue tumors, and rare rhabdoid carcinoma variants of gastroenteropancreatic, sinonasal, and genitourinary tract origin. Although a majority of SMARCB1-deficient neoplasms arise de novo, the origin of SMARCB1-deficient neoplasia in the background of a phenotypically or genetically definable differentiated SMARCB1-intact "parent neoplasm" has been convincingly demonstrated, highlighting the rare occurrence of rhabdoid tumors as "double-hit neoplasia." As a group, SMARCB1-deficient neoplasms occur over a wide age range (0 to 80 y), may be devoid of rhabdoid cells or display uniform rhabdoid morphology, and follow a clinical course that varies from benign to highly aggressive causing death within a few months irrespective of aggressive multimodality therapy. Generally applicable criteria that would permit easy recognition of these uncommon neoplasms do not exist. Diagnosis is based on site-specific and entity-specific sets of clinicopathologic, immunophenotypic, and/or molecular criteria. SMARCB1 immunohistochemistry has emerged as a valuable tool in confirming or screening for SMARCB1-deficient neoplasms. This review summarizes the different phenotypic and topographic subgroups of SMARCB1-deficient neoplasms including sporadic and familial, benign and malignant, and rhabdoid and nonrhabdoid variants, highlighting their phenotypic heterogeneity and molecular complexity. © 2014 by Lippincott Williams & Wilkins. Source

Amann K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current Opinion in Nephrology and Hypertension | Year: 2010

PURPOSE OF REVIEW: In the following study new aspects and insights into the epidemiology, pathogenesis and typical morphology of kidney involvement in thrombotic microangiopathy (TMA) are discussed. TMA comprises a spectrum of microvascular thrombosis syndromes associated with multiple pathogenetic factors, that is, typical and atypical haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), malignant hypertension, drugs or systemic autoimmune diseases or antibody-mediated rejection. RECENT FINDINGS: The present article will put particular emphasis on new pathophysiological insights into the development of TMA in the various settings. In addition, new options in the therapeutic management of TMA in atypical HUS are discussed. The pathogenesis of TMA in atypical HUS primarily involves hereditary or acquired deficiencies and disturbances of the complement system. Eculizumab is a promising new therapeutic option that has been discovered recently. SUMMARY: In HUS/TTP the kidney shows characteristic vascular changes due to endothelial damage, that is, TMA, which should be clinically and morphologically differentiated from other diseases. Recent genetic and molecular studies have shed more light on the pathogenesis of TMA in atypical HUS, that is, disturbances of various aspects of the complement system, and in TTP, that is, von Willebrand factor regulation by ADAMTS13, which are also helpful in the differential diagnosis. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Pfistermeister B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Clinical Pharmacology and Therapeutics | Year: 2014

40%). Most SPCs did not explicitly exclude adverse reactions considered not reasonably attributable to the use of the drug. Comparing SPCs of different generic brands of the same drug, only 60, 10, and 20% of the US, UK, and German SPCs, respectively, provided identical contraindications. Current SPCs contain inconsistencies and misleading data that are not compatible with the purpose of SPCs, which is to provide a basis for the safe prescription and use of drugs.Clinical Pharmacology and Therapeutics (2014); advance online publication 03 September 2014. doi:10.1038/clpt.2014.156. Source

Habets E.A.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Benesty J.,University of Quebec at Montreal
IEEE Transactions on Audio, Speech and Language Processing | Year: 2013

In general, the signal-to-noise ratio as well as the signal-to- reverberation ratio of speech received by a microphone decrease when the distance between the talker and microphone increases. Dereverberation and noise reduction algorithm are essential for many applications such as videoconferencing, hearing aids, and automatic speech recognition to improve the quality and intelligibility of the received desired speech that is corrupted by reverberation and noise. In the last decade, researchers have aimed at estimating the reverberant desired speech signal as received by one of the microphones. Although this approach has let to practical noise reduction algorithms, the spatial diversity of the received desired signal is not exploited to dereverberate the speech signal. In this paper, a two-stage beamforming approach is presented for dereverberation and noise reduction. In the first stage, a signal-independent beamformer is used to generate a reference signal which contains a dereverberated version of the desired speech signal as received at the microphones and residual noise. In the second stage, the filtered microphone signals and the noisy reference signal are used to obtain an estimate of the dereverberated desired speech signal. In this stage, different signal-dependent beamformers can be used depending on the desired operating point in terms of noise reduction and speech distortion. The presented performance evaluation demonstrates the effectiveness of the proposed two-stage approach. © 2006-2012 IEEE. Source

Pitonak M.,Czech Institute of Organic Chemistry And Biochemistry | Pitonak M.,Comenius University | Hesselmann A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Chemical Theory and Computation | Year: 2010

A new method is presented that improves the supermolecular second-order Møller-Plesset (MP2) method for dimer systems with strong dispersion interactions while preserving the generally good performance of MP2 for other types of intermolecular interactions, e.g., hydrogen-bonded systems. This is achieved by adding a correction term to the supermolecular MP2 energy that is determined using time-dependent density functional (TDDFT) response theory and that accounts for the error of the dispersion energy contained in the supermolecular MP2 method. It is shown for the S22 database set of noncovalent complexes and some potential energy curves of noncovalent bound aromatic dimers that the approach gives strong improvements over MP2 if compared to coupled-cluster singles, doubles, and perturbative triples (CCSD(T)) reference energies. An efficient computer implementation of the method is presented that is shown to scale only with the fourth power of the system size and thus leads only to a slightly higher computational cost than that of the supermolecular MP2 itself. Copyright © 2010 American Chemical Society. Source

Schuler G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Cancer Journal | Year: 2011

Dendritic cells (DCs) control the initiation and differentiation of T cells. In the steady state, DCs mediate tolerance. To achieve immunization, the tolerogenic function of DCs must be switched off by inducing their maturation with appropriate "adjuvants." Dendritic cells form a system composed of distinct subsets that differ in their expression of endocytic and signaling receptors. These subsets have different capacities to differentiate and polarize T cells and to cross-present antigen to expand CD8+ T cells. Optimization of vaccines is possible by exploiting the unique biological properties of DCs. Source

Enz R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current Drug Targets | Year: 2012

The correct targeting, localization, regulation and signaling of metabotropic glutamate receptors (mGluRs) represent major mechanisms underlying the complex function of neuronal networks. These tasks are accomplished by the formation of synaptic signal complexes that integrate functionally related proteins such as neurotransmitter receptors, enzymes and scaffold proteins. By these means, proteins interacting with mGluRs are important regulators of glutamatergic neurotransmission. Most described mGluR interaction partners bind to the intracellular C-termini of the receptors. These domains are extensively spliced and phosphorylated, resulting in a high variability of binding surfaces offered to interacting proteins. Malfunction of mGluRs and associated proteins are linked to neurodegenerative and neuropsychiatric disorders including addiction, depression, epilepsy, schizophrenia, Alzheimeŕs, Huntingtońs and Parkinsońs disease. MGluR associated signal complexes are dynamic structures that assemble and disassemble in response to the neuronal fate. This, in principle, allows therapeutic intervention, defining mGluRs and interacting proteins as promising drug targets. In the last years, several studies elucidated the geometry of mGluRs in contact with regulatory proteins, providing a solid fundament for the development of new therapeutic strategies. Here, I will give an overview of human disorders directly associated with mGluR malfunction, provide an up-to-date summary of mGluR interacting proteins and highlight recently described structures of mGluR domains in contact with binding partners. © 2012 Bentham Science Publishers. Source

Karbstein F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review C - Nuclear Physics | Year: 2010

We derive a purely fermionic no-sea effective theory, featuring positive-energy states only for the Walecka model. In contrast to the so-called mean-field theory approach with the no-sea approximation, where the Dirac sea is simply omitted from the outset, we turn to the relativistic Hartree approximation and explicitly construct a no-sea effective theory from the underlying quantum field theory. Several results obtained within these two approaches are confronted with each other. This sheds new light on the reliability of the mean-field theory with the no-sea approximation as well as the role of the Dirac sea. Restricting to 1+1 dimensions, we obtain new analytical insights into nonuniform nuclear matter. © 2010 The American Physical Society. Source

Nimmerjahn F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current topics in microbiology and immunology | Year: 2011

Genetic defects affecting the humoral immune response and especially the production of antibodies of the immunoglobulin G (IgG) isotype result in a heightened susceptibility to infections. Studies over the last years have demonstrated the crucial role of Fc-receptors for IgG (FcγRs) widely expressed on innate immune effector cells in mediating the protective function of IgG. During the last years, additional ligands interacting with FcγRs as well as additional receptors binding to IgG glycosylation variants have been identified. In this review, we discuss how the interaction of these different ligands with classical and novel Fcγ-receptors influences the immune response and which strategies microorganisms have developed to prevent them. Source

Hesselmann A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Korona T.,University of Warsaw
Physical Chemistry Chemical Physics | Year: 2011

Selected points on the potential energy surface for the complexes Rg@C 60 (Rg = He, Ne, Ar, Kr) are calculated with various theoretical methods, like symmetry-adapted perturbation theory with monomers described by density functional theory (DFT-SAPT), supermolecular Møller-Plesset theory truncated on the second order (MP2), spin-component-scaled MP2 (SCS-MP2), supermolecular density functional theory with empirical dispersion correction (DFT+Disp), and the recently developed MP2C method that improves the MP2 method for long-range electron correlation effects. A stabilization of the endohedral complex is predicted by all methods, but the depth of the potential energy well is overestimated by the DFT+Disp and MP2 approaches. On the other hand, the MP2C model agrees well with DFT-SAPT, which serves as the reference. The performance of SCS-MP2 is mixed: it produces too low interaction energies for the two heavier guests, while its accuracy for He@C60 and Ne@C60 is similar to that of MP2C. Fitting formulas for the main interaction energy components, i.e. the dispersion and first-order repulsion energies are proposed, which are applicable for both endo- and exohedral cases. For all examined methods density fitting is used to evaluate two-electron repulsion integrals, which is indispensable to allow studies of noncovalent complexes of this size. It has been found that density-fitting auxiliary basis sets cannot be used in a black-box fashion for the calculation of the first-order SAPT electrostatic energy, and that the quality of these basis sets should be always carefully examined in order to avoid an unphysical long-range behavior. Source

Ornigotti M.,Max Planck Institute for the Science of Light | Aiello A.,Max Planck Institute for the Science of Light | Aiello A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Optics Express | Year: 2013

We present a method for the realization of radially and azimuthally polarized nonparaxial Bessel beams in a rigorous but simple manner. This result is achieved by using the concept of Hertz vector potential to generate exact vector solutions of Maxwell's equations from scalar Bessel beams. The scalar part of the Hertz potential is built by analogy with the paraxial case as a linear combination of Bessel beams carrying a unit of orbital angular momentum. In this way we are able to obtain spatial and polarization patterns analogous to the ones exhibited by the standard cylindrically polarized paraxial beams. Applications of these beams are discussed. © 2013 Optical Society of America. Source

Piliarik M.,Max Planck Institute for the Science of Light | Sandoghdar V.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nature Communications | Year: 2014

Detection of single analyte molecules without the use of any label would improve the sensitivity of current biosensors by orders of magnitude to the ultimate graininess of biological matter. Over two decades, scientists have succeeded in pushing the limits of optical detection to single molecules using fluorescence. However, restrictions in photophysics and labelling protocols make this technique less attractive for biosensing. Recently, mechanisms based on vibrational spectroscopy, photothermal detection, plasmonics and microcavities have been explored for fluorescence-free detection of single biomolecules. Here, we show that interferometric detection of scattering (iSCAT) can achieve this goal in a direct and label-free fashion. In particular, we demonstrate detection of cancer marker proteins in buffer solution and in the presence of other abundant proteins. Furthermore, we present super-resolution imaging of protein binding with nanometer localization precision. The ease of iSCAT instrumentation promises a breakthrough for label-free studies of interactions involving proteins and other small biomolecules. © 2014 Macmillan Publishers Limited. Source

Suciu N.,Romanian Academy of Sciences | Suciu N.,Friedrich - Alexander - University, Erlangen - Nuremberg
Advances in Water Resources | Year: 2014

The process of diffusion in a random velocity field is the mathematical object underlying currently used stochastic models of transport in groundwater. The essential difference from the normal diffusion is given by the nontrivial correlation of the increments of the process which induces transitory or persistent dependence on initial conditions. Intimately related to these memory effects is the ergodicity issue in subsurface hydrology. These two topics are discussed here from the perspectives of ItÔ and Fokker-Planck complementary descriptions and of recent Monte Carlo studies. The latter used a global random walk algorithm, stable and free of numerical diffusion. Beyond Monte Carlo simulations, this algorithm and the mathematical frame of the diffusion in random fields allow efficient solutions to evolution equations for the probability density of the random concentration. © 2014 Elsevier Ltd. Source

Ruiz M.B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Molecular Physics | Year: 2014

In this paper we study the level of accuracy of the electronic wave functions which is necessary to describe properly the atomic effects during nuclear β-decay. In the case of the β--decay in the Li atom into Be+ ion, we compare the numerical values of the transition probabilities from the, low-lying states of the initial atom and final ion calculated using both Hylleraas-configuration interaction and configuration interaction (CI) with Slater orbital wave functions. In addition, using the CI method the transition probabilities from, and low-lying states have been calculated. The average of the absolute deviation of the transition probabilities distribution for low-lying states is <0.15%, for states it is <0v5% and larger for D and higher energy states. The numerical results demonstrate that for low-lying states the atomic effect parameters in β-decay can be calculated with sufficient accuracy using CI wave functions constructed with Slater orbitals. This result opens a new avenue for the accurate calculation of atomic effects during the β-decay in heavier atoms and molecules. © 2013 Taylor and Francis. Source

Ulrich H.G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Christian Bioethics | Year: 2015

In this article, I seek to put Engelhardt's work on Christian bioethics in the wider context. First, I discuss some fundamental issues inextricably linked to his work: the difference and relation of a "secular world" to the Christian notion of the "world," the difference and relation between the concepts of "history" given with human "progress" appearing in the field of bioethics, in contrast to the Christian understanding of God's story with His "world." These issues will be discussed in connection with the philosophical work of Karl Löwith and Jürgen Habermas, among others. Next, I critically discuss Engelhardt's genealogical account of "modernity," in order to draw-with agreement-attention to this genealogy's implications for the Christian epistemology needed for a proper understanding of human nature (the conditio humana). Discursive rational argument is not enough to secure a proper understanding of human nature, says Engelhardt. Yet, it will be shown that through the practice of Christian witness as a "good work"-which brings along with it different essential modes of understanding human nature-the Christian can encounter secular public discourse. I examine how the witness of a Christian ethos may contribute indispensable insights for public and secular discourse; this witness, I argue, implies radical consequences for medical research and treatment. Despite my general agreement with his work, one of my central theses will be that Engelhardt rests content too early in embracing an empty procedural account of the justice that can be achieved by the state. Christian witness can and ought to contribute more than this. © The Author 2015. Source

Frey B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Seminars in immunopathology | Year: 2011

Lipids in the cytoplasm membrane fulfill numerous functions. We focus on how lipid asymmetry is generated and its physiological and pathophysiological mission. The role of phosphatidylserine (PS), a prominent phospholipid that gets exposed during cell death, in health and disease as well as in the clearance process will be outlined in detail. Attraction signals, bridging molecules, and danger signals being involved in the PS-dependent clearance of apoptotic and necrotic cells and in subsequent immune modulation are presented. Furthermore, modulations of immune responses by PS-exposing cells, organisms, microparticles, and by the PS-binding protein annexin A5 are discussed. Interference with PS-dependent clearance of apoptotic tumor cells by macrophages fosters uptake and presentation of cancer antigens by dendritic cells and thereby induces specific anti-tumor immunity. The lipid composition of microvesicles is also depicted. Tumor microvesicles are often rich in PS and thereby contribute to tumor escape mechanisms. Understanding the role of PS in membranes of dying cells and microvesicles will help to develop novel drugs and treatment options for controlling immune-mediated diseases like chronic autoimmunity and cancer. Source

Maxwell P.H.,Cambridge Institute for Medical Research | Eckardt K.-U.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nature Reviews Nephrology | Year: 2016

Small-molecule stabilizers of hypoxia inducible factor (HIF) are being developed for the treatment of renal anaemia. These molecules inhibit prolyl hydroxylase domain-containing (PHD) enzymes, resulting in HIF activation and increased production of erythropoietin. Currently, renal anaemia is treated with recombinant human erythropoietin or related analogues, referred to as conventional erythropoiesis stimulating agents (ESAs). Advantages of PHD enzyme inhibitors over conventional ESAs include their oral administration and their simpler-and potentially cheaper-production. Importantly, inhibition of PHD enzymes is likely to have a range of consequences other than increasing levels of erythropoietin, and these effects could be beneficial-for instance by reducing the need for parenteral iron-but might in some instances be harmful. Several companies are currently testing PHD enzyme inhibitors in patients with renal anaemia and have reported clear evidence of efficacy without serious safety concerns. A central question that current studies are beginning to address is whether using PHD enzyme inhibitors will influence hard end points, including mortality and the rate of cardiovascular events. In terms of approaches to therapy, the exquisite specificity of conventional ESAs is a striking contrast to the pleiotropic effects of activating HIF. Excitingly, PHD inhibitors could also be useful for conditions besides renal anaemia, such as protection from ischaemic injury. © 2016 Macmillan Publishers Limited. Source

Tykwinski R.R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Chemical Record | Year: 2015

For the last 60+ years, the synthesis and study of cumulenes and polyynes have been the focus of a small, but dedicated, group of researchers. Many of the remarkable electronic, optical, and structural properties of cumulenes and polyynes had already been identified in the earliest reports. The molecular lengths achievable by the initial syntheses were, unfortunately, somewhat limited by synthetic methods available. For the past 15 years, we have worked toward expanding on the synthesis of cumulenes and polyynes through the development of new methods and stabilization motifs. As new compounds have become available, homologous series of cumulenes and polyynes have then been examined as a function of molecular length. While we are not yet there, we would like to eventually provide a general description of the sp-carbon allotrope carbyne, and this account presents some of our efforts toward this goal. © 2015 The Chemical Society of Japan and Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Agrawal B.K.,Saha Institute of Nuclear Physics | Sulaksono A.,University of Indonesia | Reinhard P.-G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nuclear Physics A | Year: 2012

We have optimized the parameters of extended relativistic mean-field model using a selected set of global observables which includes binding energies and charge radii for nuclei along several isotopic and isotonic chains and the iso-scalar giant monopole resonance energies for the 90Zr and 208Pb nuclei. The model parameters are further constrained by the available informations on the energy per neutron for the dilute neutron matter and bounds on the equations of state of the symmetric and asymmetric nuclear matter at supra-nuclear densities. Two new parameter sets BSP and IUFSU* are obtained, later one being the variant of recently proposed IUFSU parameter set. The BSP parametrization uses the contributions from the quartic order cross-coupling between ω and σ mesons to model the high density behaviour of the equation of state instead of the ω meson self-coupling as in the case of IUFSU* or IUFSU. Our parameter sets yield appreciable improvements in the binding energy systematics and the equation of state for the dilute neutron matter. The importance of the quartic order ω-σ cross coupling term of the extended RMF model, as often ignored, is realized. © 2012. Source

Willam C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Kidney International | Year: 2014

An inflammatory stimulus prior to an ischemic insult can be protective in acute kidney injury (AKI) as well as other acute organ injury models, an effect called cross-tolerance. He et al. investigated mechanisms of cross-tolerance whereby pretreatment with lipopolysaccharide (LPS) protects from a subsequent ischemic insult of the kidney. The protection was mediated by LPS-induced nuclear factor-κB and hypoxia-inducible factor-2α (HIF-2α) signaling. These results link two central cellular pathways and give new insight into HIF-mediated renoprotection in AKI models. © 2013 International Society of Nephrology. Source

Gottfried E.,University of Regensburg | Kreutz M.,University of Regensburg | Mackensen A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Seminars in Cancer Biology | Year: 2012

About a century ago Otto Warburg observed that tumor cells exhibited increased glycolysis despite the presence of oxygen and stated this metabolic shift to glycolysis as the origin of cancer cell. In the meantime it has become clear, that the altered glucose metabolism is only one piece of the tumor metabolome puzzle. In addition, amino acid, lipid and adenosine metabolism are adapted to fulfill the tumors needs for energy and generation of building blocks such as lipids and nucleotides for new cell structures. The altered tumor metabolism leads to accumulation of specific metabolites in the tumor environment and creates a favorable milieu for tumor growth, progression and metastasis. These tumor-derived metabolites are important players in immune escape mechanisms beside other known factors such as cytokines, chemokines and growth factors. A variety of metabolites re-educate immune cells and prevent an effective immune response against tumor cells. Furthermore, tumor infiltrating immune cells support tumor growth by the secretion of cytokines, growth factors and other metabolic determinants. Hence, a complex interplay of tumor metabolites, cytokines and stromal factors is active in tumors and facilitates their establishment and growth. Pharmacological blockade of tumor metabolites could overcome some limitations of cancer treatment and rescue the endogenous immune response against tumor cells. © 2012 Elsevier Ltd. Source

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. Source

Aiello A.,Max Planck Institute for the Science of Light | Aiello A.,Friedrich - Alexander - University, Erlangen - Nuremberg
New Journal of Physics | Year: 2012

When a beam of light is reflected by a smooth surface its behavior deviates from geometrical optics predictions. Such deviations are quantified by the so-called spatial and angular Goos-Hänchen (GH) and Imbert-Fedorov (IF) shifts of the reflected beam. These shifts depend upon the shape of the incident beam, its polarization and on the material composition of the reflecting surface. In this paper we suggest a novel approach that allows one to unambiguously isolate the beam-shape dependent aspects of GH and IF shifts. We show that this separation is possible as a result of some universal features of shifted distribution functions which are presented and discussed. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft. Source

Stark S.P.,Max Planck Institute for the Science of Light | Travers J.C.,Max Planck Institute for the Science of Light | Russell P.St.J.,Max Planck Institute for the Science of Light | Russell P.St.J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Optics Letters | Year: 2012

We report the formation of an ultrabroad supercontinuum down to 280 nm in the deep UV by pumping sharply tapered (5-30 mm taper lengths) solid-core photonic crystal fibers with 130 fs, 2 nJ pulses at 800 nm. The taper moves the point of soliton fission to a position where the core is narrower, a process that requires normal dispersion at the input face of the fiber. We find that the generation of deep-UV radiation is limited by strong two-photon absorption in the silica. © 2012 Optical Society of America. Source

Bogdan C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Frontiers in cellular and infection microbiology | Year: 2012

Infections with parasites of the genus Leishmania lead to a rapid, but transient activation of natural killer (NK) cells. In mice activation of NK cells requires a toll-like-receptor 9-dependent stimulation of dendritic cells (DC) which is followed by the production of IL-12. Although NK cells appear to be non-essential for the ultimate control of cutaneous and visceral leishmaniasis (VL) and can exhibit immunosuppressive functions, they form an important source of interferon (IFN)-γ, which elicits antileishmanial activity in macrophages and helps to pave a protective T helper cell response. In contrast, the cytotoxic activity of NK cells is dispensable, because Leishmania-infected myeloid cells are largely resistant to NK-mediated lysis. In human cutaneous and VL, the functional importance of NK cells is suggested by reports that demonstrate (1) a direct activation or inhibition of NK cells by Leishmania promastigotes, (2) the suppression of NK cell numbers or activity during chronic, non-healing infections, and (3) the recovery of NK cell activity following treatment. This review aims to provide an integrated view on the migration, activation, inhibition, function, and therapeutic modulation of NK cells in experimental and human leishmaniasis. Source

Pischetsrieder M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Henle T.,TU Dresden
Amino Acids | Year: 2012

Infant formulas are milk-based products, which are adapted to the composition of human milk. To ensure microbiological safety and long shelf life, infant formulas usually undergo rigid heat treatment. As a consequence of the special composition and the heat regimen, infant formulas are more prone to thermally induced degradation reactions than regular milk products. Degradation reactions observed during milk processing comprise lactosylation yielding the Amadori product lactulosyllysine, the formation of advanced glycation end products (AGEs), and protein-free sugar degradation products, as well as protein or lipid oxidation. Several methods have been developed to estimate the heat impact applied during the manufacturing of infant formulas, including indirect methods such as fluorescence analysis as well as the analysis of defined reaction products. Most studies confirm a higher degree of damage in infant formulas compared to regular milk products. Differences between various types of infant formulas, such as liquid, powdered or hypoallergenic formulas depend on the analyzed markers and brands. A considerable portion of protein degradation products in infant formulas can be avoided when process parameters and the quality of the ingredients are carefully controlled. The nutritional consequences of thermal degradation products in infant formulas are largely unknown. © Springer-Verlag 2010. Source

Rotter A.,Friedrich - Alexander - University, Erlangen - Nuremberg
European Addiction Research | Year: 2012

CB1 and CB2 receptors are influenced via exogenous and endogenous cannabinoids. To date, little is known regarding changes in receptor expression and methylation in THC (tetrahydrocannabinol) dependence. Therefore, the CB1 and CB2 receptor mRNA expression levels and promoter methylation status in the peripheral blood cells of 77 subjects (36 with THC dependence, 21 cigarette smokers and 20 nonsmokers) were assessed by quantitative real-time PCR and methylation-specific PCR. There was a significant difference in CB1 receptor expression levels between the three groups (ANOVA, p < 0.001, d.f. = 2, F = 71.3). The mean promoter methylation (%) was significantly negatively correlated with CB1 receptor mRNA expression levels (Spearman's rho: r = -0.37; p = 0.002). Using a mixed general linear model, it was demonstrated that the CB1 mRNA expression (as the dependent variable) was associated with the satisfaction with life scale (SWLS) (r = 0.101; T = 2.8; p = 0.007), craving (as measured with the VAS; r = -0.023; T = -2.3; p = 0.023) and the WHO-Assist Subscale for Cannabis consumption (r = -0.068; T = -2.4; p = 0.02). CB1 receptor expression levels and methylation status appear to be altered in subjects with THC dependence. Copyright © 2012 S. Karger AG, Basel. Source

Wekerle H.,Max Planck Institute of Neurobiology | Flugel A.,Institute for Multiple Sclerosis Research | Fugger L.,University of Oxford | Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Serreze D.,The Jackson Laboratory
Nature Medicine | Year: 2012

Animal models are indispensable for studying disease pathogenesis and discovering new treatments for human organ-specific autoimmune diseases. However, there is a need of more refined paradigms for these models. Ideally, a small-animal model should represent the clinical features of human disease in their entirety. Disease in the animals should develop spontaneously, should be followed over an extended period of time and should involve the genetic, molecular and cellular elements that contribute to human pathogenesis. © 2012 Nature America, Inc. All rights reserved. Source

Willam C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Gefasschirurgie | Year: 2011

Contrast-induced nephropathy (CIN) accounts for about one third of cases of acute kidney damage in hospitals and primarily occurs in patients with preexisting chronic diseases and risk factors, such as diabetes, hypertension and older age. The occurrence of CIN is associated with a significantly higher morbidity and mortality of patients, which underlines the need for sufficient clinical attention to identify patients at risk and to start adequate preventive measures to reduce risk of CIN. Adequate hydration with istotonic sodium chloride or bicarbonate solution is the most important measure to reduce the incidence of CIN. Further therapeutic options such as N-acetylcysteine or statins are still under debate or have not been proven to be helpful in CIN, such as diuretics or early renal replacement therapy. © Springer-Verlag 2011. Source

Wasserscheid P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Seiler M.,Evonik Industries
ChemSusChem | Year: 2011

One of the greatest challenges to science in the 21 st century is the development of efficient energy production, storage, and transformation systems with minimal ecological footprints. Due to the lack of efficient heat-transformation technologies, industries around the world currently waste energy in the gigawatt range at low temperatures (40-80°C). These energy potentials can be unlocked or used more efficiently through a new generation of smart heat pumps operating with novel ionic liquid (IL)-based working pairs. The new technology is expected to allow revolutionary technical progress in heat-transformation devices, for example, significantly higher potential efficiencies, lower specific investments, and broader possibilities to incorporate waste energy from renewable sources. Furthermore, due to drastically reduced corrosion rates and excellent thermal stabilities of the new, IL-based working pairs, the high driving temperatures necessary for multi-effect cycles such as double- or triple-effect absorption chillers, can also be realized. The details of this novel and innovative heat-transformation technology are described. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kollei I.,Friedrich - Alexander - University, Erlangen - Nuremberg | Martin A.,University of Wuppertal
Journal of Behavior Therapy and Experimental Psychiatry | Year: 2014

Background and objectives Cognitive behavioural models postulate that individuals with BDD engage in negative appearance-related appraisals and affect. External representations of one's appearance are thought to activate a specific mode of processing characterized by increased self-focused attention and an activation of negative appraisals and affect. Methods The present study used a think-aloud approach including an in vivo body exposure to examine body-related cognitions and affect in individuals with BDD (n = 30), as compared to individuals with major depression (n = 30) and healthy controls (n = 30). Participants were instructed to think aloud during baseline, exposure and follow-up trials. Results Individuals with BDD verbalized more body-related and more negative body-related cognitions during all trials and reported higher degrees of negative affect than both control groups. A weaker increase of positive body-related cognitions during exposure, a stronger increase of sadness and anger after exposure and higher levels of post-event processing, were specific processes in individuals with BDD. Limitations Individuals with major depression were not excluded from the BDD group. This is associated with a reduction of internal validity, as the two clinical groups are somewhat interwoven. Key findings need to be replicated. Conclusion The findings indicate that outcomes such as negative appearance-related cognitions and affect are specific to individuals with BDD. An external representation of one's appearance activates a specific mode of processing in BDD, manifesting itself in the absence of positive body-related cognitions, increased anger and sadness, and high levels of post-event processing. These specific processes may contribute toward maintenance of BDD psychopathology. © 2013 Elsevier Ltd. All rights reserved. Source

Titze J.,Vanderbilt University | Titze J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Kidney International | Year: 2013

Extracellular volume expansion may lead to elevated blood pressure. This long-term adaptation of the vascular bed to extracellular volume overload is considered a multifactorial and not perfectly understood 'autoregulatory' event, which is difficult to measure. In this issue, Ebah and colleagues demonstrate a direct relationship between fluid overload and pressure in CKD patients. Surprise, instead of intravascular volume, interstitial fluids and pressures were measured. Finally. © 2013 International Society of Nephrology. Source

Drey M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Wiener Medizinische Wochenschrift | Year: 2011

The causes of sarcopenia are multidimensional. The loss of fast-twitch muscle fibres exceeds the loss of slowtwitch muscle fibres and ends as a clinical relevant loss of muscle power. On a sub-cellular level, age associated changes in the mitochondria lead to functional decline of the muscle. The reduction of motor units causes muscle fibre atrophy and loss of muscle strength. Low levels of anabolic hormones and the imbalance of pro- and anti-inflammatory cytokines are responsible for changes in body composition of older adults. Reduced levels of physical activity, vitamin D and protein are highly associated with muscle loss. Sarcopenia causes loss of independence and high medical and nursing needs resulting in great economic healthcare burden. © Springer-Verlag 2011. Source

Leuchs G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Sondermann M.,Max Planck Institute for the Science of Light
Journal of Modern Optics | Year: 2013

We review recent experimental advances in the field of efficient coupling of single atoms and light in free space. Furthermore, a comparison of efficient free space coupling and strong coupling in cavity quantum electrodynamics (QED) is given. Free space coupling does not allow for observing oscillatory exchange between the light field and the atom which is the characteristic feature of strong coupling in cavity QED. Like cavity QED, free space QED does, however, offer full switching of the light field, a 180° phase shift conditional on the presence of a single atom as well as 100% absorption probability of a single photon by a single atom. Furthermore, free space cavity QED comprises the interaction with a continuum of modes. © 2013 Copyright Taylor and Francis Group, LLC. Source

Barth J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Conference proceedings : ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference | Year: 2011

Parkinson's disease (PD) is the most frequent neurodegenerative movement disorder. Early diagnosis and effective therapy monitoring is an important prerequisite to treat patients and reduce health care costs. Objective and non-invasive assessment strategies are an urgent need in order to achieve this goal. In this study we apply a mobile, lightweight and easy applicable sensor based gait analysis system to measure gait patterns in PD and to distinguish mild and severe impairment of gait. Examinations of 16 healthy controls, 14 PD patients in an early stage, and 13 PD patients in an intermediate stage were included. Subjects performed standardized gait tests while wearing sport shoes equipped with inertial sensors (gyroscopes and accelerometers). Signals were recorded wirelessly, features were extracted, and distinct subpopulations classified using different classification algorithms. The presented system is able to classify patients and controls (for early diagnosis) with a sensitivity of 88% and a specificity of 86%. In addition it is possible to distinguish mild from severe gait impairment (for therapy monitoring) with 100% sensitivity and 100% specificity. This system may be able to objectively classify PD gait patterns providing important and complementary information for patients, caregivers and therapists. Source

Schlueter S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Energy Economics | Year: 2010

In this paper we introduce a new stochastic long-term/short-term model for short-term electricity prices, and apply it to four major European indices, namely to the German, Dutch, UK and Nordic one. We give evidence that all time series contain certain periodic (mostly annual) patterns, and show how to use the wavelet transform, a tool of multiresolution analysis, for filtering purpose. The wavelet transform is also applied to separate the long-term trend from the short-term oscillation in the seasonal-adjusted log-prices.In all time series we find evidence for dynamic volatility, which we incorporate by using a bivariate GARCH model with constant correlation.Eventually we fit various models from the existing literature to the data, and come to the conclusion that our approach performs best. For the error distribution, the Normal Inverse Gaussian distribution shows the best fit. © 2010 Elsevier B.V. Source

Schmidt K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Systems and Control Letters | Year: 2010

In this paper, we introduce the idea of abstraction-based diagnosability for large-scale composed discrete event systems that consist of multiple subsystems. To this end, we determine sufficient conditions such that diagnosability of the original system follows from diagnosability of an abstracted system model on a smaller state space. In addition, we prove that also the reverse implication is true if an additional requirement for the abstraction is fulfilled. Then, we show how our method can be applied to compute abstracted models for the diagnosability verification of composed systems without enumerating the whole system state space. In this way, considerable computational savings can be achieved as illustrated by a small manufacturing system example. © 2009 Elsevier B.V. All rights reserved. Source

Goebell P.J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Knowles M.A.,St Jamess Hospital
Urologic Oncology: Seminars and Original Investigations | Year: 2010

Despite the fact that the current histopathologic classification for bladder cancer has led to improved concepts for the clinical management of the disease, key questions with regard to assessment of risk for recurrence and/or progression to invasive disease remain. In addition, response to specific therapies cannot be predicted accurately. Bladder tumors comprise a heterogeneous group with respect to both histopathology and clinical behavior. Thus, it is anticipated that a thorough knowledge and interpretation of the molecular alterations involved in tumor development and progression will lead to greater prognostic and predictive power. This may not only lead to better comprehension of the biology of the disease, but may also lead to the development of novel individualized therapies. Novel means of stratification are urgently needed to provide a new subclassification of urothelial lesions. This review discusses and summarizes the genetic alterations that have been reported in bladder cancer and relates these to the current 2-pathway model for tumor development. The molecular pathogenesis of high-grade noninvasive papillary tumors and of T1 tumors is not yet clear, and possibilities are discussed. © 2010 Elsevier Inc. Source

Schwider J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Applied Optics | Year: 2013

The 50-year life span of Applied Optics covers also approximately the time I have been engaged in optics. I started in 1962 [1] with the Institute for Optics and Spectroscopy, which was one of several Academy Institutes (mission statement: "theoria cum praxi," G. Leibniz) located in Berlin-Adlershof on the area of the first airfield in Berlin dating back to the beginning of the 20th century. © 2012 Optical Society of America. Source

Fischer J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Archive for Rational Mechanics and Analysis | Year: 2014

We derive upper bounds on the waiting time of solutions to the thin-film equation in the regime of weak slippage n ∈ [2, 32\11). In particular, we give sufficient conditions on the initial data for instantaneous forward motion of the free boundary. For n ∈ (2, 32\11), our estimates are sharp, for n = 2, they are sharp up to a logarithmic correction term. Note that the case n = 2 corresponds-with a grain of salt-to the assumption of the Navier slip condition at the fluid-solid interface. We also obtain results in the regime of strong slippage n ∈ (1,2); however, in this regime we expect them not to be optimal. Our method is based on weighted backward entropy estimates, Hardy's inequality and singular weight functions; we deduce a differential inequality which would enforce blowup of the weighted entropy if the contact line were to remain stationary for too long. © 2013 Springer-Verlag Berlin Heidelberg. Source

Sedmak T.,Johannes Gutenberg University Mainz | Sedmak T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wolfrum U.,Johannes Gutenberg University Mainz
Biology of the Cell | Year: 2011

Background information. The assembly and maintenance of cilia depend on IFT (intraflagellar transport) mediated by molecular motors and their interplay with IFT proteins. Here, we have analysed the involvement of IFT proteins in the ciliogenesis of mammalian photoreceptor cilia. Results. Electron microscopy revealed that ciliogenesis in mouse photoreceptor cells follows an intracellular ciliogenesis pathway, divided into six distinct stages. The first stages are characterized by electron-dense centriolar satellites and a ciliary vesicle, whereas the formations of the ciliary shaft and the light-sensitive outer segment discs are features of the later stages. IFT proteins were associated with ciliary apparatus during all stages of photoreceptor cell development. Conclusions. Our data conclusively provide evidence for the participation of IFT proteins in photoreceptor cell ciliogenesis, including the formation of the ciliary vesicle and the elongation of the primary cilium. In advanced stages of ciliogenesis the ciliary localization of IFT proteins indicates a role in IFT as is seen in mature cilia. A prominent accumulation of IFT proteins in the periciliary cytoplasm at the base of the cilia in these stages most probably resembles a reserve pool of IFT molecules for further delivery into the growing ciliary shaft and their subsequent function in IFT. Nevertheless, the cytoplasmic localization of IFT proteins in the absence of a ciliary shaft in early stages of ciliogenesis may indicate roles of IFT proteins beyond their well-established function for IFT in mature cilia and flagella. © 2011 Portland Press Limited. Source

Stollhofen H.,Friedrich - Alexander - University, Erlangen - Nuremberg | Stanistreet I.G.,University of Liverpool
Journal of Human Evolution | Year: 2012

Normal faults displacing Upper Bed I and Lower Bed II strata of the Plio-Pleistocene Lake Olduvai were studied on the basis of facies and thickness changes as well as diversion of transport directions across them in order to establish criteria for their synsedimentary activity. Decompacted differential thicknesses across faults were then used to calculate average fault slip rates of 0.05-0.47 mm/yr for the Tuff IE/IF interval (Upper Bed I) and 0.01-0.13 mm/yr for the Tuff IF/IIA section (Lower Bed II). Considering fault recurrence intervals of ∼1000 years, fault scarp heights potentially achieved average values of 0.05-0.47 m and a maximum value of 5.4 m during Upper Bed I, which dropped to average values of 0.01-0.13 m and a localized maximum of 0.72 m during Lower Bed II deposition. Synsedimentary faults were of importance to the form and paleoecology of landscapes utilized by early hominins, most traceably and provably Homo habilis as illustrated by the recurrent density and compositional pattern of Oldowan stone artifact assemblage variation across them. Two potential relationship factors are: (1) fault scarp topographies controlled sediment distribution, surface, and subsurface hydrology, and thus vegetation, so that a resulting mosaic of microenvironments and paleoecologies provided a variety of opportunities for omnivorous hominins; and (2) they ensured that the most voluminous and violent pyroclastic flows from the Mt. Olmoti volcano were dammed and conduited away from the Olduvai Basin depocenter, when otherwise a single or set of ignimbrite flows might have filled and devastated the topography that contained the central lake body. In addition, hydraulically active faults may have conduited groundwater, supporting freshwater springs and wetlands and favoring growth of trees. © 2011 Elsevier Ltd. Source

Krotsch J.,Ebm papst Mulfingen GmbH and Co. KG | Piepenbreier B.,Friedrich - Alexander - University, Erlangen - Nuremberg
IEEE Transactions on Industrial Electronics | Year: 2012

In external rotor permanent magnet synchronous motors with non-overlapping windings, the higher frequency harmonics of the radial forces generate considerable resonant vibrations and acoustic noise. Therefore, diversity of spatial and specifically frequency harmonic ordinal numbers of representative slot and pole number combinations are derived analytically with open circuit and under load. Amplitudes of radial force waves are calculated by means of the finite element method and 2-D Fourier analysis. The obtained results confirm the analytical investigation. Determining factors on amplitudes are studied on machines having different slot and pole numbers and double-layer windings. Higher frequency harmonics significantly depend on the pole and tooth shape as well as the current profile. With open circuit, the calculations are validated by experiments. The findings are applied to reduce the noise of a centrifugal fan. © 2006 IEEE. Source

Zahn D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Angewandte Chemie - International Edition | Year: 2010

Once bitten: Compression along the c axis of apatite-collagen composites (see picture), such as that on tooth enamel during biting, reveals a molecular mechanism that accounts for the steel-like characteristics of these composites. Simulations reveal that before eventual failure, inelastic deformation is initiated near the collagen molecules followed by pseudo-elastic deformation. The composite may undergo self-healing after release of the mechanical load. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kisch H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Angewandte Chemie - International Edition | Year: 2010

Breaking the impasse: Earlier this year Maschmeyer and Che outlined an approach for normalizing and comparing the apparent quantum yields (AQY) for hydrogen photogeneration catalyzed by semiconductor powders. In the plot of photocatalyst concentration versus AQY they proposed that the linear region was the most appropriate region for comparison. In his Correspondence Kisch refutes this proposal and states that the area at the onset of the plateau region (B) in a plot of catalyst concentration versus reaction rate is relevant. Maschmeyer and Che explain their rationale and conclude that the discussion has arisen because of different emphases in studying photocatalysis. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Dressler F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Akan O.,Koc University
IEEE Communications Magazine | Year: 2010

Bio-inspired networking techniques have been investigated since more than a decade. Findings in this field have fostered new developments in networking, especially in the most challenging domains such as handling large-scale networks, their dynamic nature, resource constraints, heterogeneity, unattended operation, and robustness. Even though this new research area started with highly theoretical concepts, it can be seen that there is also practical impact. This article aims to give an overview to the general field of bioinspired networking, introducing the key concepts and methodologies. Selected examples that outline the capabilities and the practical relevance are discussed in more detail. The presented examples outline the activities of a new community working on bio-inspired networking solutions, which is converging and becomes visible in term of the provided astonishingly efficient solutions. © 2006 IEEE. Source

Kobow K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Epilepsia | Year: 2012

DNA methylation is a covalent chromatin modification, characterized by the biochemical addition of a methyl group (-CH3) to cytosine nucleotides via a DNA methyltransferase enzyme. 5'-Methylcytosine (5-mC), frequently called the fifth base, has been implicated in genome stability, silencing of transposable elements, and repression of gene expression. Through the latter, DNA methylation dynamics broadly influence brain development, function, and aging. Aberrant DNA methylation patterns, either localized to specific gene regions or scattered throughout the genome, are associated with many neurologic disorders. Herein, we discuss the emerging role of DNA methylation in epileptogenesis and the perspectives arising from epigenetic medicine as new therapeutic strategy in difficult-to-treat epilepsies. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy. Source

Singh D.,Universiti Sains Malaysia | Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Vicknasingam B.K.,Universiti Sains Malaysia
Drug and Alcohol Dependence | Year: 2014

Background: Kratom (Mitragyna speciosa) preparations have been traditionally used in Southeast Asia for its medicinal properties. Lately, Kratom use has spread to Europe and the US, where abuse potential and health hazards increasingly emerge. This study is the first to measure systematically Kratom dependence, withdrawal symptoms, and drug craving in regular Kratom users in Malaysia. Methods: A cross-sectional survey of 293 regular Kratom users was conducted in the community across three northern peninsular states of Malaysia. The Leeds Dependence Questionnaire, Marijuana Withdrawal Checklist, and Marijuana Craving Questionnaire-Short Form were used to measure Kratom dependence, withdrawal and craving. Results: More than half of the regular users (>6 month of use) developed severe Kratom dependence problems, while 45% showed a moderate Kratom dependence. Physical withdrawal symptoms commonly experienced include muscle spasms and pain, sleeping difficulty, watery eyes/nose, hot flashes, fever, decreased appetite, and diarrhoea. Psychological withdrawal symptoms commonly reported were restlessness, tension, anger, sadness, and nervousness. The average amount of the psychoactive compound, mitragynine, in a single dose of a Kratom drink was 79. mg, suggesting an average daily intake of 276.5. mg. Regular users who consumed ≥3 glasses Kratom per day, had higher odds of developing severe Kratom dependence, withdrawal symptoms, and inability to control Kratom craving. Conclusions: The findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving. These symptoms become more severe with prolonged use and suggest a stronger control of the drug. © 2014 Elsevier Ireland Ltd. Source

Schlotzer-Schrehardt U.,Friedrich - Alexander - University, Erlangen - Nuremberg
Middle East African Journal of Ophthalmology | Year: 2011

Pseudoexfoliation (PEX) syndrome, one of the most common causes of glaucoma, represents a complex, multifactorial, late-onset disease of worldwide significance. The etiopathogenesis involves both genetic and non-genetic factors. The PEX-specific tissue alterations are caused by a generalized fibrotic matrix process, which has been characterized as a stress-induced elastosis associated with the excessive production and abnormal cross-linking of elastic microfibrils into fibrillar PEX aggregates. The identification of lysyl oxidase-like 1 (LOXL1) as a major genetic risk factor for PEX syndrome and PEX glaucoma further supports a role of elastogenesis and elastosis in the pathophysiology of PEX, as LOXL1 is a pivotal cross-linking enzyme in elastic fiber formation and stabilization. The available data suggest that LOXL1 is markedly dysregulated depending on the stage of the fibrotic process. While transient upregulation of LOXL1 during the early stages of PEX fibrogenesis participates in the formation and aggregation of abnormal PEX fiber deposits, the decreased expression of LOXL1 during the advanced stages of the disease may affect elastin metabolism and promote elastotic processes, e.g. in the lamina cribrosa, predisposing to glaucoma development. However, in view of the low penetrance of the PEX-associated risk variants of LOXL1, other genetic and/or environmental factors must contribute to the risk of developing the PEX phenotype. Some evidence exists for the contribution of additional genes with relatively small effects, e.g. clusterin (CLU), contactin-associated protein-like 2 (CNTNAP2), apolipoprotein E (APOE), glutathione S-transferases (GSTs), and tumor necrosis factor-alpha (TNFA), in certain study populations. Several environmental conditions associated with PEX, such as oxidative stress as well as pro-fibrotic cytokines and growth factors, can regulate expression of LOXL1 and elastic proteins in vitro and may therefore act as co-modulating external factors. Ultimately, both detection and functional characterization of yet unidentified genetic and non-genetic factors may lead to the development of more precise screening tools for the risk of PEX glaucoma. Source

Wasserthal L.T.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Experimental Biology | Year: 2012

In Calliphoridae and Drosophilidae, the dorsal vessel (heart and aorta with associated venous channels) is the only connection between the thorax and the abdomen. Hemolymph oscillates between the compartments by periodic heartbeat reversal, but both the mechanism and its influence on hemocoelic and tracheal pressure have remained unclear. The pumping direction of the heart regularly reverses, with a higher pulse rate during backward compared with forward pumping. A sequence of forward and backward pulse periods lasts approximately 34s. Pulse rate, direction, velocity and the duration of heartbeat periods were determined by thermistor and electrophysiological measurements. For the first time, heartbeat-induced pressure changes were measured in the hemocoel and in the tracheal system of the thorax and the abdomen. The tracheal pressure changed from subatmospheric during backward heartbeat to supra-atmospheric during forward heartbeat in the thorax and inversely in the abdomen. The heartbeat reversals were coordinated with slow abdominal movements with a pumping stroke at the beginning of the forward pulse period. The pressure effect of the pumping stroke was visible only in the abdomen. Periodic hemolymph shift and abdominal movements resulted in pressure changes in the hemocoel and tracheal system alternating in the thorax and abdomen, suggesting an effect on respiratory gas exchange. © 2012. Published by The Company of Biologists Ltd. Source

Enz R.,Friedrich - Alexander - University, Erlangen - Nuremberg
Frontiers in Molecular Neuroscience | Year: 2012

Metabotropic glutamate receptors (mGluRs) regulate intracellular signal pathways that control several physiological tasks, including neuronal excitability, learning and memory. This is achieved by the formation of synaptic signal complexes, in which mGluRs assemble with functionally related proteins such as enzymes, scaffolds and cytoskeletal anchor proteins. Thus, mGluR associated proteins actively participate in the regulation of glutamatergic neurotransmission. Importantly, dysfunction of mGluRs and interacting proteins may lead to impaired signal transduction and finally result in neurological disorders, e.g. night blindness, addiction, epilepsy, schizophrenia, autism spectrum disorders and Parkinson ́s disease. In contrast to solved crystal structures of extracellular N-terminal domains of some mGluR types, only a few studies analyzed the conformation of intracellular receptor domains. Intracellular C31 termini of most mGluR types are subject to alternative splicing and can be further modified by phosphorylation and SUMOylation. In this way, diverse interaction sites for intracellular proteins that bind to and regulate the glutamate receptors are generated. Indeed, most of the known mGluR binding partners interact with the receptors' C-terminal domains. Within the last years, different laboratories analyzed the structure of these domains and described the geometry of the contact surface between mGluR C-termini and interacting proteins. Here, I will review recent progress in the structure characterization of mGluR C-termini and provide an up-to-date summary of the geometry of these domains in contact with binding partners. © 2012 Enz. Source

Baltzer P.A.T.,Medical University of Vienna | Dietzel M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Radiology | Year: 2013

Purpose: To perform a systematic review and meta-analysis to estimate the diagnostic performance of breast proton magnetic resonance (MR) spectroscopy in differentiating benign from malignant lesions and to identify variables that influence the accuracy of MR spectroscopy. Materials and Methods: A comprehensive search of the PubMed database was performed on articles listed until January 6, 2012. The Medical Subject Headings and text words for the terms "breast," "spectroscopy," and "magnetic resonance" were used. Investigations including more than 10 patients at 1.5 T or 3.0 T applying one-dimensional single-voxel MR spectroscopy or spatially resolved MR spectroscopy for differentiation between benign and malignant breast lesions were eligible. A reference standard had to be established either by means of histopathologic examination or imaging follow-up of 12 or more months. Statistical analysis included pooling of diagnostic accuracy, control for data inhomogeneity, and identification of publication bias. Results: Nineteen studies were used for general data pooling. The studies included a total of 1183 patients and 1198 lesions (773 malignant, 452 benign). Pooled sensitivity and specificity were 73% (556 of 761; 95% confidence interval [CI]: 64%, 82%) and 88% (386 of 439; 95% CI: 85%, 91%), respectively. The pooled diagnostic odds ratio (DOR) was 34.30 (95% CI: 16.71, 70.43). For breast cancers versus benign lesions, the area under the symmetric summary receiver operating characteristic curve of MR spectroscopy was 0.88, and the Q*index was 0.81. There was evidence of between-studies heterogeneity regarding sensitivity and DOR (P < .0001). No significant influences of higher field strength, postcontrast acquisition, or qualitative versus quantitative MR spectroscopy measurements were identified. Egger testing confirmed significant publication bias in studies including small numbers of patients (P < .0001). Conclusion: Breast MR spectroscopy shows variable sensitivity and high specificity in the diagnosis of breast lesions, independent from the technical MR spectroscopy approach. Because of significant publication bias, pooled diagnostic measures might be overestimated. © RSNA, 2013. Source

Tschammer N.,Friedrich - Alexander - University, Erlangen - Nuremberg
Bioorganic and Medicinal Chemistry Letters | Year: 2014

The highly constitutively active G protein-coupled receptor US28 of human cytomegalovirus (HCMV) is thought to camouflage agonism by mediating constitutive endocytosis. With the use of the US28Δ300 mutant, which is largely devoid of constitutive internalization, I have demonstrated that the coupling of the receptor to its downstream signaling partners is responsible for the inverse agonism to agonism efficacy switch in some small-weight ligands of US28. © 2014 Elsevier Ltd. All rights reserved. Source

Mattner J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current Opinion in Immunology | Year: 2013

Natural killer T (NKT) cells represent an innate-like lymphocyte population endowed with unique antigen recognition and tissue distribution features. Their abundance in the microvascular compartments of the liver allows NKT cells to immediately respond to lipid antigens and soluble factors circulating through the portal vein system by releasing tremendous amounts of different cytokines and chemokines. Subsequently, dependent on the nature of the lipid antigen encountered as well as the accessory signal(s) provided, NKT cells not only contribute to the maintenance of immune tolerance, but also direct adverse immune reactions locally and systemically. Focusing on their potent immunomodulatory features and their interactions with various innate and adaptive immune cells, the role of NKT cells in perpetuating the loss of liver-specific immune tolerance will be discussed. © 2013 Elsevier Ltd. Source

Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Muller C.P.,Kings College London | Schumann G.,Kings College London
Behavioral and Brain Sciences | Year: 2011

Abstract Most people who are regular consumers of psychoactive drugs are not drug addicts, nor will they ever become addicts. In neurobiological theories, non-addictive drug consumption is acknowledged only as a necessary prerequisite for addiction, but not as a stable and widespread behavior in its own right. This target article proposes a new neurobiological framework theory for non-addictive psychoactive drug consumption, introducing the concept of drug instrumentalization. Psychoactive drugs are consumed for their effects on mental states. Humans are able to learn that mental states can be changed on purpose by drugs, in order to facilitate other, non-drug-related behaviors. We discuss specific instrumentalization goals and outline neurobiological mechanisms of how major classes of psychoactive drugs change mental states and serve non-drug-related behaviors. We argue that drug instrumentalization behavior may provide a functional adaptation to modern environments based on a historical selection for learning mechanisms that allow the dynamic modification of consummatory behavior. It is assumed that in order to effectively instrumentalize psychoactive drugs, the establishment of and retrieval from a drug memory is required. Here, we propose a new classification of different drug memory subtypes and discuss how they interact during drug instrumentalization learning and retrieval. Understanding the everyday utility and the learning mechanisms of non-addictive psychotropic drug use may help to prevent abuse and the transition to drug addiction in the future. © 2011 Cambridge University Press. Source

Beuers U.,Tytgat Institute for Liver and Intestinal Research | Kremer A.E.,Tytgat Institute for Liver and Intestinal Research | Kremer A.E.,Friedrich - Alexander - University, Erlangen - Nuremberg | Bolier R.,Tytgat Institute for Liver and Intestinal Research | Elferink R.P.J.O.,Tytgat Institute for Liver and Intestinal Research
Hepatology | Year: 2014

Pruritus is a common symptom in patients with cholestatic liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, or hereditary pediatric cholestatic disorders and may accompany, although less frequently, many other liver diseases. Recent findings indicate that lysophosphatidic acid (LPA), a potent neuronal activator, and autotaxin (ATX; ectonucleotide pyrophosphatase/phosphodiesterase 2), the enzyme which forms LPA, may form a key element of the long-sought pruritogenic signaling cascade in cholestatic patients suffering from itch. Serum ATX, but no other pruritogen candidate studied so far, correlates with pruritus intensity and responds to therapeutic interventions. In this comprehensive review, we provide a short update on actual insights in signal transmission related to pruritus and discuss pruritogen candidates in cholestasis. We also summarize evidence-based and guideline-approved as well as experimental therapeutic approaches for patients suffering from pruritus in cholestasis. (Hepatology 2014;60:399-407) © 2014 by the American Association for the Study of Liver Diseases. Source

Matzel K.E.,Friedrich - Alexander - University, Erlangen - Nuremberg
Colorectal Disease | Year: 2011

Aim Indications for sacral nerve stimulation (SNS) for faecal incontinence have expanded over the last decade. This report aims to determine the clinical outcome of the current use of SNS in the treatment of faecal incontinence. Its objective is also to review the most recent role of SNS in patients with anal sphincter lesions. Method The literature was searched using Medline and Cochrane databases. The search was restricted to publications in English. For the analysis, studies with <25 patients were excluded. For SNS in patients with sphincter defects, all papers were included. Results Thirteen publications on the clinical outcome of SNS were included. Nine papers were identified reporting the application of SNS in patients with a morphological sphincter lesion. The most common outcome measures of clinical efficacy were frequency of incontinence using the Cleveland Clinic Incontinence Score. All studies demonstrated highly improved function across all outcome measures and improvement was statistically significant in all. Outcomes remain stable at long-term follow up. In patients with sphincteric gaps ranging from 17 to 180°, SNS was clinically effective at short-term follow up. The size of the gap appears to have no impact on outcome. Conclusion SNS has evolved to become a clinical efficient therapy applicable across a wide spectrum of causes of faecal incontinence with reproducible results. SNS can be considered to be an essential part of the current surgical treatment algorithm for faecal incontinence. © 2011 The Author. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland. Source

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

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

Kuzmin D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Computational Physics | Year: 2014

In this paper, we present a collection of algorithmic tools for constraining high-order discontinuous Galerkin (DG) approximations to hyperbolic conservation laws. We begin with a review of hierarchical slope limiting techniques for explicit DG methods. A new interpretation of these techniques leads to an unconditionally stable implicit algorithm for steady-state computations. The implicit global problem for the mean values (coarse scales) has the computational structure of a finite volume method. The constrained derivatives (fine scales) are obtained by solving small local problems. The interscale transfer operators provide a two-way iterative coupling between the solutions to the global and local problems. Another highlight of this paper is a new approach to compatible gradient limiting for the Euler equations of gas dynamics. After limiting the conserved quantities, the gradients of the velocity and energy density are constrained in a consistent manner. Numerical studies confirm the accuracy and robustness of the proposed algorithms. © 2013 Elsevier Inc. Source

Karl M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Quintessence international (Berlin, Germany : 1985) | Year: 2012

Passive fit between restorations and implants is considered a significant factor in preventing mechanical and biologic failures in implant dentistry. Since impression taking and master cast fabrication have been shown to cause substantial errors, it was the aim of this study to evaluate the effect of intraoral scanning on the passivity of fit of three-unit cement-retained implant-supported fixed dental prostheses (FDPs). Conventional and optical impressions (n = 10) of an in vitro situation with two implants in the mandibular left quadrant were made. Based on the scans, 10 FDP frameworks were CAD/CAM fabricated from zirconia ceramic; stereolithographic casts were also made. On both the stereolithographic casts and the casts obtained from the conventional impressions, 10 frameworks were waxed and cast in dental training alloy. Subsequently, all samples were cemented on the in vitro model, while the strains emerging were recorded for statistical analysis (MANOVA with Pillai trace; β = .05). The restorations fabricated on the stereolithographic casts showed significantly lower levels of strain than the conventionally fabricated ones (P = .013). No significant difference could be found between conventionally and CAD/CAM-fabricated frameworks (P = .080). Intraoral digitization of dental implants appears to be at least as precise as conventional impression taking and master cast fabrication using prefabricated transfer components and laboratory analogs. Source

Stangel M.,Hannover Medical School | Linker R.A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Expert Review of Clinical Pharmacology | Year: 2013

Treatments for multiple sclerosis (MS) are only partially effective and most require a parenteral route of administration and/or may have severe side effects. Dimethyl fumarate is the active compound of BG-12 recently licensed for the treatment of relapsing-remitting MS. The pivotal Phase III trials have demonstrated an approximately 50% reduction of relapse rates compared with placebo paralleled by a reduction in new lesion formation on MRI. A dose of 240 mg two-times a day had an optimal effect. Flushing and gastrointestinal symptoms (diarrhea, abdominal pain, nausea) were common adverse events in the first month(s) of treatment. Severe side effects were not more common than in the placebo group for a treatment period of 2 years. The mode of action is not exactly clear and both immunomodulatory effects and an activation of the transcription factor Nrf2 are suggested. This new oral drug will be a welcome addition to existing MS treatments. © 2013 Informa UK Ltd. Source

Albrecht H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Clinical Gastroenterology | Year: 2016

BACKGROUND:: Recent studies have analyzed the potential of advanced endoscopic imaging techniques for differentiating hyperplastic and adenomatous colorectal lesions. Latest endoscopic resection techniques now also allow for treatment of more advanced staged lesions including treatment of early cancerous lesions. AIMS:: To assess the potential of the i-scan technology to differentiate between adenomatous polyps and advanced staged neoplasia. METHODS:: Consecutive patients undergoing colonoscopy at a tertiary referral center were included. After a dedicated training, participating endoscopists underwent a review of 298 unknown images of colonic lesions to assess colorectal lesion histology. RESULTS:: Overall accuracy for prediction of advanced staged neoplasia was 92.2% (sensitivity: 94.2%, specificity 90.9%). The positive and negative predictive values were calculated as 87.5% and 95.9%, respectively. The κ-value for differentiating adenomatous polyps and advanced staged neoplasia was 0.8193 (0.7894 to 0.8492). Intraobserver agreement was calculated with a κ-value of 0.9301 (0.8875 to 0.9727). CONCLUSIONS:: Accurate interpretation of i-scan images for prediction of advanced colorectal neoplasia can successfully be performed even by nonexpert endoscopists with a high overall accuracy and excellent interobserver agreements. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source

Saremi F.,University of Southern California | Achenbach S.,Friedrich - Alexander - University, Erlangen - Nuremberg
American Journal of Roentgenology | Year: 2015

OBJECTIVE. In this article, we review the histopathologic classification of coronary atherosclerotic plaques and describe the possibilities and limitations of CT regarding the evaluation of coronary artery plaques. CONCLUSION. The composition of atherosclerotic plaques in the coronary arteries displays substantial variability and is associated with the likelihood for rupture and downstream ischemic events. Accurate identification and quantification of coronary plaque components on CT is challenging because of the limited temporal, spatial, and contrast resolutions of current scanners. Nonetheless, CT may provide valuable information that has potential for characterization of coronary plaques. For example, the extent of calcification can be determined, lipidrich lesions can be separated from more fibrous ones, and positive remodeling can be identified. © American Roentgen Ray Society. Source

Gugat M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Systems and Control Letters | Year: 2014

We study a semilinear mildly damped wave equation that contains the telegraph equation as a special case. We consider Neumann velocity boundary feedback and prove the exponential stability of the closed loop system. We show that for vanishing damping term in the partial differential equation, the decay rate of the system approaches the rate for the system governed by the wave equation without damping term. In particular, this implies that arbitrarily large decay rates can occur if the velocity damping in the partial differential equation is sufficiently small. © 2014 Elsevier B.V. All rights reserved. Source

Booth M.J.,University of Oxford | Booth M.J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Light: Science and Applications | Year: 2014

Adaptive optics is becoming a valuable tool for high resolution microscopy, providing correction for aberrations introduced by the refractive index structure of specimens. This is proving particularly promising for applications that require images from deep within biological tissue specimens. We review recent developments in adaptive microscopy, including methods and applications. A range of advances in different microscope modalities is covered and prospects for the future are discussed. © 2014 CIOMP. Source

McLean M.H.,U.S. National Cancer Institute | Neurath M.F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Durum S.K.,U.S. National Cancer Institute
Inflammatory Bowel Diseases | Year: 2014

Inflammatory bowel disease accounts for significant patient morbidity in the Western world. Several immunosuppressive therapies are available but are associated with potential significant adverse effects. In addition, there remains a cohort of patients with refractory or relapsing disease. Therefore, the search for novel therapeutic agents continues. In this review, we evaluate the role of a number of designated cytokines that are candidates in the pathogenesis of inflammatory bowel disease and discuss how their manipulation has been explored as a therapeutic strategy for this disease. The interleukins (ILs) chosen for discussion reflect those that currently show most promise as future therapeutic targets, as well as discussing the role of some of the most recently identified ILs, such as IL-27, IL-33, IL-35, and IL-22, in this context Copyright © 2013 Crohn's & Colitis Foundation of America, Inc. Source

Gao G.,Friedrich - Schiller University of Jena | Gao G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wondraczek L.,Friedrich - Schiller University of Jena
Journal of Materials Chemistry C | Year: 2013

We report on near-infrared (NIR) down-conversion by energy transfer between Mn2+ and Yb3+ in crystalline Zn1.96-xGeO 4+1/2x:Mn0.04Ybx. In the Zn2GeO 4 lattice, intrinsic defect transitions and Mn2+ ions act as broadband spectral sensitizers by absorbing UV-Vis (280-500 nm) photons and transferring the absorbed energy to Yb3+ centers in a cooperative down-conversion process. The Yb3+ acceptor is then the source of NIR emission at a wavelength of ∼1000 nm. Efficient energy transfer is reflected by a sharp decrease in the excited state lifetime and green photoluminescence (PL) from tetrahedrally coordinated Mn2+ with increasing Yb 3+ concentration. PL-excitation spectra of NIR luminescence from Yb3+ are identical to those of from IVMn2+. A maximal energy transfer efficiency (ETE) from Mn2+ to Yb3+ and a total theoretical quantum efficiency of 63.8% and 163.8%, respectively, are estimated. © 2013 The Royal Society of Chemistry. Source

Engelke K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2012

PURPOSE OF REVIEW: To give an overview of advanced in-vivo imaging techniques for assessing bone quality beyond bone mineral density that have considerably advanced in recent years. RECENT FINDINGS: Quantitative computed tomography and finite element analysis improve fracture risk prediction at the spine, and help to better understand the pathophysiology of skeletal diseases and response to therapy by quantifying bone mineral density in different bone compartments, determining bone strength, and assessing bone geometry. With new high-resolution techniques, trabecular structure at the spine, forearm, and tibia, and cortical porosity at the forearm and tibia can be measured. Hip structure analysis and trabecular bone score have extended the usefulness of dual X-ray absorptiometry. SUMMARY: New advanced three-dimensional imaging techniques to quantify bone quality are mature and have proven to be complimentary methods to dual X-ray absorptiometry enhancing our understanding of bone metabolism and treatment. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Bauer S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2012

To manage respiratory motion in image-guided interventions a novel sparse-to-dense registration approach is presented. We apply an emerging laser-based active triangulation (AT) sensor that delivers sparse but highly accurate 3-D measurements in real-time. These sparse position measurements are registered with a dense reference surface extracted from planning data. Thereby a dense displacement field is reconstructed which describes the 4-D deformation of the complete patient body surface and recovers a multi-dimensional respiratory signal for application in respiratory motion management. The method is validated on real data from an AT prototype and synthetic data sampled from dense surface scans acquired with a structured light scanner. In a study on 16 subjects, the proposed algorithm achieved a mean reconstruction accuracy of +/- 0.22 mm w.r.t. ground truth data. Source

Maueroder C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Cell Death and Differentiation | Year: 2016

In this study, we deploy a doxycycline-dependent suicide switch integrated in a tumor challenge model. With this experimental setup, we characterized the immunological consequences of cells dying by four distinct cell death stimuli in vivo. We observed that apoptotic cell death induced by expression of the truncated form of BH3 interacting-domain death agonist (tBid) and a constitutively active form of caspase 3 (revC3), respectively, showed higher immunogenicity than cell death induced by expression of the tuberculosis-necrotizing toxin (TNT). Our data indicate that the early release of ATP induces the silent clearance of dying cells, whereas the simultaneous presence of ‘find me’ signals and danger-associated molecular patterns (DAMPs) promotes inflammatory reactions and increased immunogenicity. This proposed model is supported by findings showing that the production and release of high concentrations of IL-27 by bone-marrow-derived macrophages (BMDM) is limited to BMDM exposed to those forms of death that simultaneously released ATP and the DAMPs heat-shock protein 90 (HSP90) and high-mobility group box-1 protein (HMGB1). These results demonstrate that the tissue microenvironment generated by dying cells may determine the subsequent immune response.Cell Death and Differentiation advance online publication, 4 March 2016; doi:10.1038/cdd.2016.4. © 2016 Macmillan Publishers Limited Source

Deutscher J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Automatica | Year: 2015

In this article the output regulation problem for boundary controlled parabolic systems with spatially varying coefficients is solved by applying the backstepping approach. Thereby, the outputs to be controlled are not required to be measurable and can be pointwise, distributed or boundary quantities, whereas the measurement is located at the boundary. By solving the state feedback regulator problem in the backstepping coordinates regulator equations with a simple structure result, so that their analysis and solution is facilitated. The output feedback regulator design is completed by determining a finite-dimensional reference observer and an infinite-dimensional disturbance observer. For the latter a backstepping approach is presented that consists of a triangular decoupling in the backstepping coordinates. This allows a systematic design and the explicit derivation of directly verifiable existence conditions for the disturbance observer. It is shown that for the resulting compensator the separation principle holds implying output regulation for the exponentially stable closed-loop system with a prescribed stability margin. The output regulation results of the article are illustrated by means of a parabolic system with an in-domain pointwise controlled output. © 2015 Elsevier Ltd. Source

Laurin M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Chemical Education | Year: 2013

QVibeplot is a software program that automatically generates two-dimensional visualizations of molecular vibrations. The representations show the changes of bond lengths, angles, and torsions occurring upon a vibration. This is consistent with the experimentalist's understanding of molecular vibrations that makes a distinction between stretching and deformation modes. Two-dimensionality is achieved by basing the representation on a skeletal formula of the molecule. The program also displays the spectrum and the list of frequencies. The phase and amplitude are indicated as well, providing a comprehensive visualization of molecular vibrations. The software is available online as a free and open-source software. © 2013 The American Chemical Society and Division of Chemical Education, Inc. Source

Foltz W.U.,Friedrich - Alexander - University, Erlangen - Nuremberg
Basic research in cardiology | Year: 2012

Pressure overload is associated with cardiac hypertrophy and electrical remodeling. Here, we investigate the effects of the antioxidant N-acetylcysteine (NAC) on the cellular cardiac electrophysiology of female Sprague-Dawley rats with ascending aortic stenosis (AS). Rats were treated with NAC (1 g/kg body weight) or control solution 1 week before the intervention and in the week following AS or sham operation. Seven days after the operation, blood pressure and left ventricular pressure were measured before the heart was excised. Single cells were isolated from epicardial and endocardial layers of the left ventricular free wall and investigated using the whole-cell patch-clamp technique. Systolic blood pressure and left ventricular peak pressure were not significantly altered in the NAC group. NAC reduced the increase (p < 0.001) in the relative left ventricular weight (p < 0.05) as well as the increase (p < 0.001) in cell capacitance in epicardial (p < 0.05), but not in endocardial myocytes of AS animals. The L-type Ca(2+) current (I (CaL)) was significantly increased by AS in epicardial (+19 % at 0 mV, p < 0.01) but not in endocardial myocytes. NAC completely prevented this increase in I (CaL) (p < 0.01). The current density of the transient outward K(+) current (I (to)) was not affected by AS or NAC. Action potential duration to 90 % repolarization was significantly prolonged in epicardial (p < 0.01) as well as in endocardial (p < 0.001) cells of AS animals. NAC prevented the AP prolongation in epicardial myocytes only (p < 0.05). We conclude that reducing oxidative stress in pressure overload can prevent electrical remodeling and ameliorate hypertrophy in epicardial but not in endocardial myocytes. Source

Slany R.K.,Friedrich - Alexander - University, Erlangen - Nuremberg
Oncogene | Year: 2016

Mixed lineage leukemia caused by MLL fusion proteins is still a mostly incurable disease. Research on novel treatment strategies has gained momentum in the last years with the elucidation of the molecular mechanisms underlying the transforming potential of these powerful oncoproteins. This review summarizes the recent developments in this area including new attempts to treat MLL in a rational way by exploiting the biochemical vulnerabilities of the leukemogenic process.Oncogene advance online publication, 29 February 2016; doi:10.1038/onc.2016.30. © 2016 Macmillan Publishers Limited Source

Schuler G.,Friedrich - Alexander - University, Erlangen - Nuremberg
European Journal of Immunology | Year: 2010

DC initiate and regulate T-cell immunity and are thus the key to optimization of all types of vaccines. Insights into DC biology offer many opportunities to enhance immunogenicity. In this Viewpoint, I discuss some recent developments and findings that are of immediate relevance for the clinical development of cancer vaccines. In addition, I emphasize my personal view that we should explore the potential of adoptively transferred DC (i.e. DC vaccination) as cancer vaccines by performing two-armed trials that address critical variables and by delivering antigens via mRNA-transfected DC. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. Source

Hahn I.,Friedrich - Alexander - University, Erlangen - Nuremberg
2010 1st Symposium on Sensorless Control for Electrical Drives, SLED 2010 | Year: 2010

It is well known that rotor position detection at very low speed and at standstill is only possible with signal injection methods, because at vanishing speed the different methods using the induced voltage (back EMF methods) are not suitable. All signal injection methods need as a prerequisite the existence of a magnetic anisotropy of the machine over a wide range of operating conditions. This document presents first the basic theory of electrical machines to derive the needed machine properties which are the prerequisite for rotor position detection at standstill with signal injection methods. Different machine designs with concentrated windings will be analyzed in view of the differential magnetic anisotropy by means of finite element field calculations. Results from prototype measurements will also be presented and compared with the theoretical findings. © 2010 IEEE. Source

Eichfelder G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Mathematical Programming | Year: 2010

In this work nonlinear non-convex multiobjective bilevel optimization problems are discussed using an optimistic approach. It is shown that the set of feasible points of the upper level function, the so-called induced set, can be expressed as the set of minimal solutions of a multiobjective optimization problem. This artificial problem is solved by using a scalarization approach by Pascoletti and Serafini combined with an adaptive parameter control based on sensitivity results for this problem. The bilevel optimization problem is then solved by an iterative process using again sensitivity theorems for exploring the induced set and the whole efficient set is approximated. For the case of bicriteria optimization problems on both levels and for a one dimensional upper level variable, an algorithm is presented for the first time and applied to two problems: a theoretical example and a problem arising in applications. © 2008 Springer-Verlag. Source

Achenbach S.,Friedrich - Alexander - University, Erlangen - Nuremberg | Raggi P.,Emory University
European Heart Journal | Year: 2010

Modern computed tomography (CT) systems afford sufficient spatial and temporal resolution for imaging of the heart and coronary arteries. The detection of coronary artery calcium (CAC) is relatively straightforward and it is applied to detect and quantify subclinical coronary atherosclerosis even in asymptomatic individuals. A large body of evidence has accumulated that uniformly attests to a high predictive value of CAC for future cardiac events. More complex data acquisition protocols, which require higher spatial and temporal resolution, specific patient preparation, and the intravenous injection of contrast agent, allow to perform coronary CT angiography (CTA). With CTA, the presence of luminal stenoses and, given sufficient image quality, calcified as well as non-calcified atherosclerotic plaque can be visualized. Initial studies have shown that certain plaque characteristics, such as positive remodelling or very low CT attenuation, are associated with plaque vulnerability. So far, the available clinical data are not sufficient to draw specific conclusions as to the risk-benefit ratio of contrast-enhanced coronary CTA for risk prediction, especially for asymptomatic individuals. Hence, CTA is currently not recommended for risk stratification purposes. However, the technology of coronary CTA continues to evolve at a rapid pace and clinical applications for plaque imaging and characterization may become possible in the future. © 2010 The Author. Source

Wasza J.,Friedrich - Alexander - University, Erlangen - Nuremberg
Medical image computing and computer-assisted intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention | Year: 2012

Over the last years, range imaging (RI) techniques have been proposed for patient positioning and respiration analysis in motion compensation. Yet, current RI based approaches for patient positioning employ rigid-body transformations, thus neglecting free-form deformations induced by respiratory motion. Furthermore, RI based respiration analysis relies on non-rigid registration techniques with run-times of several seconds. In this paper we propose a real-time framework based on RI to perform respiratory motion compensated positioning and non-rigid surface deformation estimation in a joint manner. The core of our method are pre-procedurally obtained 4-D shape priors that drive the intra-procedural alignment of the patient to the reference state, simultaneously yielding a rigid-body table transformation and a free-form deformation accounting for respiratory motion. We show that our method outperforms conventional alignment strategies by a factor of 3.0 and 2.3 in the rotation and translation accuracy, respectively. Using a GPU based implementation, we achieve run-times of 40 ms. Source

Munstedt H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Rheology | Year: 2014

Rheology has achieved a strong position for the characterization of polymeric materials during the last 40 years. Dynamic-mechanical measurements are widely used for this purpose. On several examples, this paper demonstrates the potential of creep-recovery whose application has still been rather limited. In many cases, dynamic-mechanical experiments suffer from the fact that for several reasons, the angular frequencies applied are not chosen low enough to reach the terminal regime for which relationships between rheological quantities and molecular parameters have been established. In creep and a subsequent recovery, the time scales can be extended into the stationary regime in the linear range of deformation, and therefore, creep recovery is an efficient method to directly determine the zero-shear viscosity η0 and the linear steady-state recoverable compliance Je 0. For a polymer melt with long relaxation times, it is shown how time-dependent creep data converted into dynamic-mechanical quantities can be used to extend the frequency scale to the terminal regime. The power of Je 0 and its temperature dependence is demonstrated for the analysis of the branching structure of a polymer. Furthermore, from such kind of measurements, interesting insights into the interactions between particles and matrix molecules in filled polymeric materials were obtained. As shown in elongational experiments, the steady state of deformation at a constant stress is reached at shorter times than at the corresponding constant strain rate. The experimental consequences are discussed. Another interesting aspect of creep is that a constant stress implies a constant capillary number. The advantage of this experimental condition for investigations of the droplet deformation in polymer blends is demonstrated. © 2014 The Society of Rheology. Source

Mughrabi H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Procedia Engineering | Year: 2010

In the first part, some fundamental issues that have been under discussion for a long time will be revisited, namely the effect of the cyclic slip mode on the fatigue-induced dislocation distributions, the origin and effect of cyclic slip irreversibilities and their relation to fatigue life and, finally, cyclic strain localization and fatigue crack initiation in persistent slip bands. In the second part, some topics that have recently found increasing interest will be discussed such as the cyclic deformation and fatigue behaviour of ultrafine-grained and nanostructured materials and the microstructural mechanisms that govern fatigue life of ductile and high-strength materials in the range of ultrahigh cycle fatigue. Some general conclusions will be drawn. © 2010 Published by Elsevier Ltd. Source

Baltzer P.A.T.,Medical University of Vienna | Dietzel M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Kaiser W.A.,University Hospital Jena
European Radiology | Year: 2013

Objectives: In the face of multiple available diagnostic criteria in MR-mammography (MRM), a practical algorithm for lesion classification is needed. Such an algorithm should be as simple as possible and include only important independent lesion features to differentiate benign from malignant lesions. This investigation aimed to develop a simple classification tree for differential diagnosis in MRM. Methods: A total of 1,084 lesions in standardised MRM with subsequent histological verification (648 malignant, 436 benign) were investigated. Seventeen lesion criteria were assessed by 2 readers in consensus. Classification analysis was performed using the chi-squared automatic interaction detection (CHAID) method. Results include the probability for malignancy for every descriptor combination in the classification tree. Results: A classification tree incorporating 5 lesion descriptors with a depth of 3 ramifications (1, root sign; 2, delayed enhancement pattern; 3, border, internal enhancement and oedema) was calculated. Of all 1,084 lesions, 262 (40.4 %) and 106 (24.3 %) could be classified as malignant and benign with an accuracy above 95 %, respectively. Overall diagnostic accuracy was 88.4 %. Conclusions: The classification algorithm reduced the number of categorical descriptors from 17 to 5 (29.4 %), resulting in a high classification accuracy. More than one third of all lesions could be classified with accuracy above 95 %. Key Points: • A practical algorithm has been developed to classify lesions found in MR-mammography. • A simple decision tree consisting of five criteria reaches high accuracy of 88.4 %. • Unique to this approach, each classification is associated with a diagnostic certainty. • Diagnostic certainty of greater than 95 % is achieved in 34 % of all cases. © 2013 European Society of Radiology. Source

Thiel C.T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Rauch A.,University of Zurich
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2011

Cartilage-hair hypoplasia and anauxetic dysplasia are two autosomal recessive skeletal dysplasias characterized by different degrees from metaphyseal to spondylo-meta-epiphyseal dysplasia and variable additional features including predisposition to cancer, anemia, immunodeficiency, and gastrointestinal malabsorption and Hirschsprung's disease. Both are caused by mutations in the untranslated RMRP gene, which forms the RNA subunit of the RNase MRP complex. This complex is involved in the ribosome assembly by cleavage of 5.8S rRNA, cell cycle control by Cyclin B2 mRNA cleavage at the end of mitosis, processing the mitochondrial RNA, and forming a complex with hTERT suggesting a possible involvement in expression regulation by siRNA synthesis. The degree of skeletal dysplasia correlates mainly with the rRNA cleavage activity, whereas significantly diminished mRNA cleavage activity is a prerequisite for immunodeficiency. Thus, the clinical phenotype emerges in most cases of the combined effect on the respective effect on RNase MRP function. © 2010 Elsevier Ltd. All rights reserved. Source

Tsogoeva S.B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Mini-Reviews in Medicinal Chemistry | Year: 2010

The present mini-review highlights the recent developments on different classes of synthetic hybrids of natural and/or unnatural bioactive compounds, the utilization of which is very promising, as distinct features of each component can be hybridized and their properties leveraged. Particular stress is put on the respective mode of action and the corresponding rationale behind covalent combinations of various bioactive agents to increase their therapeutic potential, facilitate their administration, to reduce harmful side effects and/or to overcome the problem of multi-drug resistance. This rather recent approach has already found applications in the development of new anti-cancer, anti-Alzheimer, antimalaria, anti-microbial therapeutics and other novel compounds with unprecedented bioactivity. © 2010 Bentham Science Publishers Ltd. Source

Autonomic dysfunction is common but frequently overlooked in multiple sclerosis (MS) patients. The case of a Tako-Tsubo cardiomyopathy on which this commentary is based shows that centrally triggered autonomic dysfunction may be the first life-threatening manifestation of MS. © The Author(s), 2016. Source

Sorrentino R.,University of Rome La Sapienza | Bockmann R.A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Fiorillo M.T.,University of Rome La Sapienza
Molecular Immunology | Year: 2014

The HLA-B27 is historically studied as a susceptibility factor in spondyloarthropathies and, primarily, in ankylosing spondylitis (AS). Over the recent years however, it has been rediscovered as protective factor against some severe viral infections. This is due to the high capacity of virus-specific, HLA-B27-restricted CD8+ T cells for both intrinsic (i.e. polyfunctionality, high avidity, low sensitivity to Treg cell-mediated suppression) and extrinsic (i.e. rapid and efficient antigen processing and presentation) factors. It is tempting to speculate that these two aspects are not independent and that the association of B27 molecules to autoimmunity is the downside of this superior functional efficacy which, in given genetic backgrounds and environmental conditions, can support a chronic inflammation leading to spondyloarthropathies. Still, the pathogenic role of HLA-B27 molecules in AS is elusive. Here, we focus on the biology of HLA-B27 from the genetics to the biochemistry and to the structural/dynamical properties of B27:peptide complexes as obtained from atomistic molecular dynamics simulation. Overall, the results point at the antigen presentation as the key event in the disease pathogenesis. In particular, an extensive comparison of HLA-B*2705 and B*2709 molecules, that differ in a single amino acid (Asp116 to His116) and are differentially associated with AS, indicates that position 116 is crucial for shaping the entire peptide-presenting groove. © 2013 Elsevier Ltd. Source

Atreya R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Goetz M.,University Hospital of Tuebingen
Nature Reviews Gastroenterology and Hepatology | Year: 2013

Molecular imaging is a novel field in gastroenterology that uses fluorescently labelled probes to specifically highlight neoplastic lesions on the basis of their molecular signature. The development of molecular imaging has been driven by the need to improve endoscopic diagnosis and by progress in targeted therapies in gastrointestinal oncology to provide individualized treatment, which coincides with progress in endoscopy techniques and further miniaturization of detection devices. Different exogenous molecular probes for imaging include labelled antibodies, oligopeptides, affibodies™ (Affibody AB, Bromma, Sweden), aptamers and activatable probes. Molecular imaging has been evaluated in two major indications: many trials have studied molecular imaging as a red flag technique to improve detection of lesions in wide-field imaging; on the other hand, microscopic analysis has been investigated for in vivo characterization of the molecular fingerprint of tumours with the ultimate goal of assessing the likelihood of response to targeted therapy. This Review focusses on the applications of molecular imaging that have immediate potential for translational science or imminent transition into clinical practice of gastrointestinal endoscopy. Source

Rempel A.,RAS Institute of Solid State Chemistry | Magerl A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta Crystallographica Section A: Foundations of Crystallography | Year: 2010

Experimentally it is observed that nanomaterials from II-VI compounds like CdS have a high density of stacking faults. It is argued that these are not crystal defects but rather that they represent a characteristic feature of nanomaterials. © 2010 International Union of Crystallography Printed in Singapore-all rights reserved. Source

Zolk O.,Friedrich - Alexander - University, Erlangen - Nuremberg
Annals of Medicine | Year: 2012

Considerable interindividual variability in clinical efficacy is recognized in the treatment of type 2 diabetes mellitus with the biguanide metformin. Metformin is a substrate of organic cation transporters, which play important roles in gastrointestinal absorption, renal and biliary elimination, and distribution to target sites of substrate drugs. This raises the question of whether genetic variations in these transporters affect efficacy and risk of adverse events associated with metformin use. In this review, the pharmacogenetics of metformin is discussed in the light of the most recent literature. Overall, results from healthy volunteers support the notion that metformin pharmacokinetics can be affected by polymorphisms in genes encoding organic cation transporters. When considering the glycemic response to metformin in patients, however, the likely multifactorial nature of metformin response masks the effects of transporter polymorphisms observed in some clinical studies. © 2012 Informa UK, Ltd. Source

Nimmerjahn F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Cancer immunity | Year: 2012

Monoclonal antibodies of the immunoglobulin G (IgG) isotype have become a well-established therapeutic tool for the targeting of malignant cells in tumor patients. Despite tremendous success in the treatment of lymphoma and breast cancer, it has also become clear that we may not be able to further improve antibody therapy of cancer by simply generating more tumor-specific antibodies with a higher affinity. Instead, the work of many groups in the past years suggests that optimizing the recruitment of effector functions provided by the adaptive and innate immune systems via engineering of the IgG constant domain may hold great promise to achieve enhanced therapeutic activities. A major goal in cancer therapy would be to initiate adaptive immune responses to the patient's tumor that would result in long-term protection against recurrence. The use of immunostimulatory antibodies shows great promise in stimulating adaptive immune responses. Surprisingly, recent studies also implicate an important role for the antibody constant domain in the activity of these molecules in vivo, opening up new possibilities to further improve the activity of immunomodulatory antibodies by Fc engineering. Source

Zirlik S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society | Year: 2013

The incidence of the obstructive sleep apnoea syndrome (OSAS) is rising as it is often associated with obesity. Actually, the adipose tissue is working as an endocrine organ with complex interactions. Recently, many adipokines such as omentin-1 were discovered. The role of omentin-1 in the pathogenesis of OSAS has not been clearly determined. Melatonin has a known influence on the sleep and wake rhythm. The data on the involvement of melatonin in OSAS are rare. Therefore we evaluated the changes in plasma levels of omentin-1 and melatonin before and after continuous positive airway pressure (CPAP) therapy in OSA patients. 10 patients with newly diagnosed OSAS were included in the study. They underwent diagnostic polysomnography with blood drawings in a 2 hour interval for 24 hours. In the second night sufficient CPAP therapy was established. After three months of CPAP therapy the measurements were repeated. As controls 10 healthy volunteers were recruited. The same blood analysis and a polygraphic measurement were made and compared with the patients. OSA patients showed significantly higher omentin-1 plasma levels (17.22±13.94 versus 9.24±4.85 ng/ml, p<0.05). After three months of therapy the plasma levels of omentin-1 decreased toward the values observed in the controls at 8.00 a.m. Melatonin showed the usual peak at 2.00 a.m. in the volunteer group. OSA patients showed a later peak of melatonin at 6.00 a.m. which returned to 2.00 a.m. after CPAP therapy. We conclude that omentin as well as melatonin seem to be involved in pathogenesis of OSAS. To what exent, further studies will have to face that question. Source

Kok J.F.,Cornell University | Parteli E.J.R.,Federal University of Ceara | Parteli E.J.R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Michaels T.I.,Southwest Research Institute | Karam D.B.,University Pierre and Marie Curie
Reports on Progress in Physics | Year: 2012

The transport of sand and dust by wind is a potent erosional force, creates sand dunes and ripples, and loads the atmosphere with suspended dust aerosols. This paper presents an extensive review of the physics of wind-blown sand and dust on Earth and Mars. Specifically, we review the physics of aeolian saltation, the formation and development of sand dunes and ripples, the physics of dust aerosol emission, the weather phenomena that trigger dust storms, and the lifting of dust by dust devils and other small-scale vortices. We also discuss the physics of wind-blown sand and dune formation on Venus and Titan. © 2012 IOP Publishing Ltd. Source

Ornigotti M.,Friedrich - Schiller University of Jena | Aiello A.,Max Planck Institute for the Science of Light | Aiello A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Optics Express | Year: 2014

Traditionally, the angular momentum of light is calculated for "bullet-like" electromagnetic wave packets, although in actual optical experiments "pencil-like" beams of light are more commonly used. The fact that a wave packet is bounded transversely and longitudinally while a beam has, in principle, an infinite extent along the direction of propagation, renders incomplete the textbook calculation of the spin/orbital separation of the angular momentum of a light beam. In this work we demonstrate that a novel, extra surface part must be added in order to preserve the gauge invariance of the optical angular momentum per unit length. The impact of this extra term is quantified by means of two examples: a Laguerre-Gaussian and a Bessel beam, both circularly polarized. © 2014 Optical Society of America. Source

Pranzetti D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

The Turaev-Viro state sum model provides a covariant spin foam quantization of three-dimensional Riemannian gravity with a positive cosmological constant Λ. We complete the program to canonically quantize the theory in the BF formulation using the formalism of loop quantum gravity. In particular, we show first how quantum group structures arise from the requirement of the constraint algebra to be anomaly free. This allows us to generalize the construction of the physical scalar product, from the Λ=0 case, in the presence of a positive Λ. We prove the equivalence between the covariant and canonical quantizations by recovering the spin foam amplitudes. © 2014 American Physical Society. Source

Brauer L.,Friedrich - Alexander - University, Erlangen - Nuremberg
Biomedizinische Technik. Biomedical engineering | Year: 2012

The oral cavity along with the teeth and the surrounding gingival epithelium is open to the oral environment and is thus exposed to multiple microbiological and pathogenic influences. To prevent permanent inflammatory processes such as gingivitis or parodontitis, an efficient defense system is necessary to sustain the physiological function of the oral cavity. Surfactant proteins (SPs), originally known from pulmonary tissue, are important players of the immune system and, beyond this, support the stability and rheology of gas or fluid interphases. Here we evaluate the expression and presence of SPs (SP-A, SP-B, SP-C, and SP-D) in human gingiva and saliva. Messenger RNA expression of SP-A, SP-B, SP-C, and SP-D was analyzed by reverse transcriptase-polymerase chain reaction in healthy gingiva. The distribution of all four SPs was further determined with monoclonal antibodies using Western blot analyses and immunohistochemistry in healthy and pathologically changed tissues samples obtained during biopsies and in saliva of volunteers. Our results indicate that SP-A, SP-B, SP-C, and SP-D are peptides produced by healthy gingiva that reveal a changed expression pattern in cases of gingival disease. Based on the known direct and indirect antimicrobial effects, SP-A and SP-D appear to be involved in immune defense within the oral cavity especially in direct proximity of teeth. Gingiva affected by bacterial inflammation (gingivitis) seems to increase expression of SPs. As a result, the rheology of saliva may be changed especially at the crest of the gingival epithelium to support the function of antimicrobial substances present in saliva. Furthermore, SPs could assist in pellicle formation on teeth, which needs to be determined in further experiments. Source

Muller C.P.,Friedrich - Alexander - University, Erlangen - Nuremberg | Homberg J.R.,Donders Institute for Brain
Behavioural Brain Research | Year: 2015

The use of psychoactive drugs is a wide spread behaviour in human societies. The systematic use of a drug requires the establishment of different drug use-associated behaviours which need to be learned and controlled. However, controlled drug use may develop into compulsive drug use and addiction, a major psychiatric disorder with severe consequences for the individual and society. Here we review the role of the serotonergic (5-HT) system in the establishment of drug use-associated behaviours on the one hand and the transition and maintenance of addiction on the other hand for the drugs: cocaine, amphetamine, methamphetamine, MDMA (ecstasy), morphine/heroin, cannabis, alcohol, and nicotine. Results show a crucial, but distinct involvement of the 5-HT system in both processes with considerable overlap between psychostimulant and opioidergic drugs and alcohol. A new functional model suggests specific adaptations in the 5-HT system, which coincide with the establishment of controlled drug use-associated behaviours. These serotonergic adaptations render the nervous system susceptible to the transition to compulsive drug use behaviours and often overlap with genetic risk factors for addiction. Altogether we suggest a new trajectory by which serotonergic neuroadaptations induced by first drug exposure pave the way for the establishment of addiction. © 2014 Elsevier B.V. Source

Amato D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Behavioural Brain Research | Year: 2015

Antipsychotic drugs are the treatment of choice in schizophrenia. Since the discovery of chlorpromazine, several generations of antipsychotic drugs have been developed with disparate mechanism of action and complex binding profile. Although the modifications of their mechanisms have translated into decreased side effects, their superior therapeutic efficacy is often debated. Furthermore, the lack of clear criteria to define antipsychotic drugs as typical or atypical is delaying the development of new compounds with innovative mechanisms of actions. There is general agreement that we are abusing dopaminergic based criteria to evaluate the newly available compounds although they are targeting several other neurotransmitter systems. The present work will overview the antipsychotic drugs effects on serotonin levels as measured with microdialysis in the rat brain. A functional association among therapeutic mechanisms of antipsychotic drugs, their serotonin receptors affinities and serotonin level changes will be attempted. The primary ambition of this investigation is to provide an exhaustive reference for who is interested, at any levels, in antipsychotic drugs effects on cortical and subcortical serotonin output. © 2014 Elsevier B.V. Source

Brandner S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta neurochirurgica. Supplement | Year: 2012

Posthemorrhagic hydrocephalus requiring permanent ventriculoperitoneal shunt placement is a major complication of aneurysmal subarachnoid hemorrhage (SAH). High S100B serum and cerebrospinal fluid (CSF) levels are considered to reflect the severity of brain injury. We prospectively assessed whether S100B levels in serum and CSF were predictive parameters for permanent shunt requirement following aneurysmal SAH. In patients suffering from aneurysmal SAH and treated with an external ventricular drain (EVD), S100B levels in serum and CSF were measured daily as long as the EVD was in place. S100B levels of patients who passed their EVD challenge were compared with those patients who required a permanent ventriculoperitoneal shunt placement. Out of 68 patients included in the study, 43 patients (63.2%) passed the EVD challenge and in 25 patients (36.8%) permanent ventriculoperitoneal shunting was performed. Group comparison revealed that in patients who required shunt placement, S100B was significantly higher in CSF (p < 0.05 at days 2, 4, 6, 10; p < 0.005 at days 1, 3, 5, 7, 8, 9) and serum (p < 0.05 at days 4-7) compared with patients who could be weaned from the EVD. Assessment of S100B levels in CSF and serum may be useful as a predictive parameter for shunt dependency in patients with posthemorrhagic hydrocephalus following aneurysmal SAH. Source

Thies M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

The massless Gross-Neveu and chiral Gross-Neveu models are well known examples of integrable quantum field theories in 1+1 dimensions. We address the question of whether integrability is preserved if one either replaces the four-fermion interaction in fermion-antifermion channels by a dual interaction in fermion-fermion channels, or if one adds such a dual interaction to an existing integrable model. The relativistic Hartree-Fock-Bogoliubov approach is adequate to deal with the large-N limit of such models. In this way, we construct and solve three integrable models with Cooper pairing. We also identify a candidate for a fourth integrable model with maximal kinematic symmetry, the "perfect" Gross-Neveu model. This type of field theories can serve as exactly solvable toy models for color superconductivity in quantum chromodynamics. © 2014 American Physical Society. Source

Lunemann J.D.,University of Zurich | Nimmerjahn F.,Friedrich - Alexander - University, Erlangen - Nuremberg | Dalakas M.C.,National and Kapodistrian University of Athens
Nature Reviews Neurology | Year: 2015

Intravenous immunoglobulin (IVIg)-a preparation of polyclonal serum IgG pooled from thousands of blood donors-has been used for nearly three decades, and is proving to be an efficient anti-inflammatory and immunomodulatory treatment for a growing number of neurological diseases. Evidence from controlled clinical trials has established IVIg as a first-line therapy for Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy. IVIg is also an effective rescue therapy in some patients with worsening myasthenia gravis, and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. IVIg has been tested in some neurodegenerative disorders, but a controlled study in Alzheimer disease yielded disappointing results. Despite its widespread use and therapeutic success, the mechanisms of action of IVIg are poorly understood. Several hypotheses, based on the function of either the variable or constant IgG fragments, have been proposed to explain IVIg's immunomodulatory activity. This Review highlights emerging data on the mechanisms of action of IVIg related to its anti-inflammatory activity, especially that involving the cellular FcÎ 3 receptors and Fc glycosylation. We also summarize recent trials in neurological diseases, discuss potential biomarkers of efficacy, offer practical guidelines on administration, and provide a rationale for experimental trials in neuroinflammatory disorders. © 2015 Macmillan Publishers Limited. Source

Ritter A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Optics Express | Year: 2014

The shifted angular spectrum method allows a reduction of the number of samples required for numerical off-axis propagation of scalar wave fields. In this work, a modification of the shifted angular spectrum method is presented. It allows a further reduction of the spatial sampling rate for certain wave fields. We calculate the benefit of this method for spherical waves. Additionally, a working implementation is presented showing the example of a spherical wave propagating through a circular aperture. © 2014 Optical Society of America. Source

Agaimy A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Head and Neck Pathology | Year: 2013

Fat-containing tumors of the salivary glands are uncommon. Their wide histological spectrum varies from pure lipomatous neoplasms similar to their cutaneous and soft tissue counterparts to mixed lipoepithelial lesions specific to the salivary glands. With few exceptions, these uncommon lesions affect mainly the elderly, with a mean age at presentation of ≥50 years and show a predilection for males. A few cases occur in childhood; some of them represent congenital lesions. In decreasing order of frequency, ordinary (soft-tissue type) lipoma, oncocytic lipoadenoma, non-oncocytic sialolipoma, and pleomorphic adenoma/myoepithelioma with extensive lipometaplasia are the main variants of fat containing tumors encountered in the salivary glands. While pleomorphic adenoma/myoepithelioma with lipometaplasia behave in the same way as their non-fat-containing counterparts, other lipomatous salivary gland tumors listed above are cured with simple excision and do not carry a risk of recurrence. Other lipoma variants (spindle cell lipoma, osteolipoma, fibrolipoma, angiolipoma, pleomorphic lipoma, lipoblastoma and hibernoma) are exceptionally rare in the salivary gland. Atypical lipomatous tumors/liposarcoma have been only rarely reported in the salivary gland and they behave in a similar fashion to their soft-tissue counterparts. Diffuse lipomatosis and lobular fatty atrophy are the two tumor-like lesions that might closely mimic sialolipoma, particularly in limited biopsy material without knowledge of the gross findings. This review summarizes the clinicopathological features of the main types of salivary fat-containing lesions and discusses their differential diagnoses. © 2013 Springer Science+Business Media New York. Source

Absmanner B.,University of Regensburg | Stadler R.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hammes U.Z.,University of Regensburg
Frontiers in Plant Science | Year: 2013

Sedentary plant parasitic nematodes such as root-knot nematodes and cyst nematodes induce giant cells or syncytia, respectively, in their host plant's roots. These highly specialized structures serve as feeding sites from which exclusively the nematodes withdraw nutrients. While giant cells are symplastically isolated and obtain assimilates by transporter-mediated processes syncytia are massively connected to the phloem by plasmodesmata. To support the feeding sites and the nematode during their development, phloem is induced around syncytia and giant cells. In the case of syncytia the unloading phloem consists of sieve elements and companion cells and in the case of root knots it consists exclusively of sieve elements. We applied immunohistochemistry to identify the cells within the developing phloem that responded to auxin and cytokinin. Both feeding sites themselves did not respond to either hormone. We were able to show that in root knots an auxin response precedes the differentiation of these auxin responsive cells into phloem elements. This process appears to be independent of B-type Arabidopsis response regulators. Using additional markers for tissue identity we provide evidence that around giant cells protophloem is formed and proliferates dramatically. In contrast, the phloem around syncytia responded to both hormones. The presence of companion cells as well as hormone-responsive sieve elements suggests that metaphloem development occurs. The implication of auxin and cytokinin in the further development of the metaphloem is discussed. © 2013 Absmanner, Stadler and Hammes. Source

Kuehnle D.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Health Economics | Year: 2014

Recent studies examining the effect of family income on child health have been unable to account for the endogeneity of income. Using data from a British cohort study, we address this gap by exploiting exogenous variation in local labour market characteristics to instrument for family income. We estimate the causal effect of family income on different measures of child health and explore the role of potential transmission mechanisms. We find that income has a very small but significant causal effect on subjective child health and no significant effect on chronic health conditions, apart from respiratory illnesses. Using the panel structure, we show that the timing of income does not matter for young children. Moreover, our results provide further evidence that parental health does not drive a spurious relationship between family income and child health. Our study implies that financial transfers are unlikely to deliver substantial improvements in child health. © 2014 Elsevier B.V. Source

Brabec C.J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Brabec C.J.,Bavarian Center for Applied Energy Research | Gowrisanker S.,Plextronics, Inc. | Halls J.J.M.,Solar Press Ltd. | And 3 more authors.
Advanced Materials | Year: 2010

Solution-processed bulk heterojunction organic photovoltaic (OPV) devices have gained serious attention during the last few years and are established as one of the leading next generation photovoltaic technologies for low cost power production. This article reviews the OPV development highlights of the last two decades, and summarizes the key milestones that have brought the technology to today's efficiency performance of over 7%. An outlook is presented on what will be required to drive this young photovoltaic technology towards the next major milestone, a 10% power conversion efficiency, considered by many to represent the efficiency at which OPV can be adopted in wide-spread applications. With first products already entering the market, sufficient lifetime for the intended application becomes more and more critical, and the status of OPV stability as well as the current understanding of degradation mechanisms will be reviewed in the second part of this article. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kuramatsu J.B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Neurosurgery | Year: 2012

Recent studies have focused on antiplatelet (AP) use in intracerebral hemorrhage (ICH) patients. Several outcome predictors have been debated, but influences on mortality and outcome still remain controversial, especially for different ICH locations. To investigate the characteristics and functional outcome of ICH patients with reported regular AP use according to hemorrhage locations. This retrospective analysis included 210 consecutive spontaneous ICH patients. Clinical data including the preadmission status, initial presentation, neuroradiological data, treatment, and outcome were evaluated. Analyses were calculated for AP use vs non-AP use according to hematoma locations, and multivariate models were calculated for hematoma expansion and unfavorable (modified Rankin Scale = 4-6) long-term functional outcome (at 1 year). For all AP users ICH volume was significantly larger, 27.7 mL (interquartile range 7.4-66.1) vs 16.8 mL (interquartile range 4.2-44.7); (P = .032). Analyses showed an increased mortality for AP users at 90 days and 1 year (P = .036; P = .008). Multivariately, for all ICH patients, prior AP use was independently associated with hematoma expansion (odds ratio [OR] 3.61; P = .026) and poorer functional outcome at 1 year (OR 3.82, P = .035). In deep ICH patients, AP use was an independent predictor of an unfavorable functional outcome at 1 year (OR 4.75, P = .048). Hematoma expansion and more frequent unfavorable long-term functional outcome were independently associated with prior AP use for all patients, and in deep ICH patients AP use was an independent predictor of an unfavorable long-term functional outcome. Source

Hoelscher-Obermaier J.,Friedrich - Alexander - University, Erlangen - Nuremberg | Van Loock P.,Max Planck Institute for the Science of Light
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

We consider entanglement swapping with general mixed two-mode Gaussian states and calculate the optimal gains for a broad class of such states including those states most relevant in communication scenarios. We show that, for this class of states, entanglement swapping adds no additional mixedness; that is, the ensemble-average output state has the same purity as the input states. This implies that, by using intermediate entanglement swapping steps, it is, in principle, possible to distribute entangled two-mode Gaussian states of higher purity as compared to direct transmission. We then apply the general results on optimal Gaussian swapping to the problem of quantum communication over a lossy fiber and demonstrate that, in contrast to the negative conclusions in the literature, swapping-based schemes in fact often perform better than direct transmission for high input squeezing. However, an effective transmission analysis reveals that the hope for improved performance based on optimal Gaussian entanglement swapping is spurious since the swapping does not lead to an enhancement of the effective transmission. This implies that the same or better results can always be obtained using direct transmission in combination with, in general, less squeezing. © 2011 American Physical Society. Source

Dunne G.V.,University of Connecticut | Thies M.,Friedrich - Alexander - University, Erlangen - Nuremberg
Physical Review Letters | Year: 2013

We find the general solution to the time-dependent Hartree-Fock problem for the Gross-Neveu models, with both discrete (GN2) and continuous [Nambu-Jona-Lasinio (NJL2)] chiral symmetry. We find new multibaryon, multibreather, and twisted breather solutions, and show that all GN2 baryons and breathers are composed of constituent twisted kinks of the NJL 2 model. © 2013 American Physical Society. Source

Penafiel J.,University of Groningen | Maron L.,INSA Toulouse | Harder S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Angewandte Chemie - International Edition | Year: 2015

Organocalcium compounds have been reported as efficient catalysts for various alkene transformations. In contrast to transition metal catalysis, the alkenes are not activated by metal-alkene orbital interactions. Instead it is proposed that alkene activation proceeds through an electrostatic interaction with a Lewis acidic Ca2+. The role of the metal was evaluated by a study using the metal-free catalysts: [Ph2N-Me4N+] and [Ph3C-][Me4N- ]. These "naked" amides and carbanions can act as catalysts in the conversion of activated double bonds (C=O and C=N) in the hydroamination of Ar-N=C=O and R-N=C=N=R (R=alkyl) by Ph2NH. For the intramolecular hydroamination of unactivated C=C bonds in H2C=CHCH2CPh2CH2NH2 the presence of a metal cation is crucial. A new type of hybrid catalyst consisting of a strong organic Schwesinger base and a simple metal salt can act as catalyst for the intramolecular alkene hydroamination. The influence of the cation in catalysis is further evaluated by a DFT study. © 2015 Wiley-VCH Verlag GmbH &Co. KGaA, Weinheim. Source

Lohbauer U.,Friedrich - Alexander - University, Erlangen - Nuremberg
Materials | Year: 2010

Glass ionomer cements (GICs) are clinically attractive dental materials that have certain unique properties that make them useful as restorative and luting materials. This includes adhesion to moist tooth structures and base metals, anticariogenic properties due to release of fluoride, thermal compatibility with tooth enamel, biocompatibility and low toxicity. The use of GICs in a mechanically loaded situation, however, has been hampered by their low mechanical performance. Poor mechanical properties, such as low fracture strength, toughness and wear, limit their extensive use in dentistry as a filling material in stress-bearing applications. In the posterior dental region, glass ionomer cements are mostly used as a temporary filling material. The requirement to strengthen those cements has lead to an ever increasing research effort into reinforcement or strengthening concepts. © 2010 by the authors. Source

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

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

Son N.T.,Linkoping University | Bickermann M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Janzen E.,Linkoping University
Applied Physics Letters | Year: 2011

In unintentionally Si-doped AlN, the electron paramagnetic resonance (EPR) spectrum of the Si shallow donor (g=1.9905) was observed in darkness at room temperature. The temperature dependence of the EPR signal suggests that Si in AlN is a DX center with the DX- state lying at ∼78 meV below the neutral shallow donor state. With such relatively small thermal activation energy, Si is expected to behave as a shallow dopant in AlN at normal device operating temperatures. © 2011 American Institute of Physics. Source

Jin X.,University of Kiel | Gotz M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Wille S.,University of Kiel | Wille S.,Universitatsklinikum Schleswig Holstein Campus Kiel | And 3 more authors.
Advanced Materials | Year: 2013

The stress-induced photo-luminescence response of tetrapodal shaped ZnO filler embedded in a silicone elastomer is used to demonstrate a novel concept for self-reporting materials. Applied tensile stress can be followed in composites with low and high filler fractions by measuring the photoluminescence response of the T-ZnO. The deformation of the interlocked ZnO network appears to be essential for the self-reporting mechanism. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Leschke H.,Friedrich - Alexander - University, Erlangen - Nuremberg | Leschke H.,University of Hagen | Sobolev A.V.,University College London | Spitzer W.,University of Hagen
Physical Review Letters | Year: 2014

In a remarkable paper [Phys. Rev. Lett. 96, 100503 (2006)], Gioev and Klich conjectured an explicit formula for the leading asymptotic growth of the spatially bipartite von Neumann entanglement entropy of noninteracting fermions in multidimensional Euclidean space at zero temperature. Based on recent progress by one of us (A.V.S.) in semiclassical functional calculus for pseudodifferential operators with discontinuous symbols, we provide here a complete proof of that formula and of its generalization to Rényi entropies of all orders α>0. The special case α=1/2 is also known under the name logarithmic negativity and often considered to be a particularly useful quantification of entanglement. These formulas exhibiting a "logarithmically enhanced area law" have been used already in many publications. © 2014 American Physical Society. Source

Mughrabi H.,Friedrich - Alexander - University, Erlangen - Nuremberg
International Journal of Fatigue | Year: 2013

Depending on material and details of cyclic loading conditions, fatigue damage develops and spreads by various modes of crack initiation and subsequent crack growth. In order to gain a deeper understanding of the underlying microstructural mechanisms, many details must be considered. The present study focuses on just a few specific aspects, namely the role of cyclic slip irreversibilities, the significance of fatigue crack initiation in high and ultrahigh cycle fatigue (HCF, UHCF) and, finally the analysis of non-linear effects of elasticity and compliance of fatigued specimens, as a promising non-destructive in situ fatigue damage diagnosis tool. Selected experimental data obtained on different materials will be considered to illustrate the issues named above. © 2012 Elsevier B.V. All rights reserved. Source

Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg
Swiss Medical Weekly | Year: 2012

This article is to share some of the key scientific insights made by Dr Barry Bresnihan in rheumatoid arthritis. Dr Bresnihan elaborated new and visionary concepts in arthritis research, which still influence current thinking. He had been particularly dedicated to investigate the inflammatory tissue (synovitis) in RA, which he considered as a clue to understand the pathogenesis of this disease. He thereby pioneered the concept of synovial biopsy as a technique, which allows to directly analyse synovitis and has stimulated many other rheumatologists in joining his efforts. He was also dedicated to understand why synovitis triggers bone destruction in joints and started to work on defining the molecular interactions between inflammation and the bone. This article picks up some of the major insights achieved by Dr Bresnihan's work and how these findings influenced today's understanding of arthritis. Source

Nimmerjahn F.,Friedrich - Alexander - University, Erlangen - Nuremberg
Seminars in Hematology | Year: 2016

Current treatment strategies in patients with immunothrombocytopenia (ITP) include immunosuppression and the stimulation of platelet production. Research over the last decade has emphasized the important role of Fc-receptors as key molecules responsible for autoantibody-mediated platelet depletion, allowing for a more specific targeting of this pathway instead of a generalized suppression of the immune system. This short review will discuss approaches aiming at interfering with key steps in this pathway, such as preventing the interaction of the platelet autoantibody immune complex with phagocytic cells, enhancing the clearance of autoantibodies, and interfering with or modulating the signaling pathways responsible for innate immune effector cell activation. © 2016 Elsevier Inc.. Source

Mompiou F.,CNRS Toulouse Center for Materials Elaboration and Structural Studies | Caillard D.,CNRS Toulouse Center for Materials Elaboration and Structural Studies | Legros M.,CNRS Toulouse Center for Materials Elaboration and Structural Studies | Mughrabi H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta Materialia | Year: 2012

Loading-unloading cycles have been performed on ultrafine-grained (UFG) aluminium inside a transmission electron microscope (TEM). The interaction of dislocations with grain boundaries, which is supposed to be at the origin of the inelastic behaviour of this class of materials, differs according to the main character of the dislocation segments involved in pile-ups. Pile-ups are formed by spiral sources and lead to the incorporation of dislocations into grain boundaries (GBs) during loading. Upon unloading, partial re-emission of dislocations from GBs can be observed. Stress and strain measurements performed during these in situ TEM loading-unloading experiments are in agreement with the rather large inelastic reverse strains observed during unloading in loading-unloading tests on bulk macroscopic UFG aluminium specimens. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. Source

Greil P.,Friedrich - Alexander - University, Erlangen - Nuremberg
Advanced Engineering Materials | Year: 2015

Peter Greil, 60, is professor of materials science at the University of Erlangen, Germany. He received his Dipl.Ing. in mineralogy in 1980 and a PhD in metallurgy in 1982 from University of Stuttgart, Germany. Before joining Erlangen University in 1993 he worked for the Max-Planck-Institute for Metals Research and held a position as an associate professor for advanced ceramics at the Technical University of Hamburg-Harburg. Greils research on processing of ceramics has resulted in more than 350 papers and 45 patents. His major fields of research include processing of ceramics and composites, and microstructure and properties of cellular and biomorphous ceramics. Nano-carbon materials attained considerable scientific interest due to their unique physicochemical properties. Much less reports can be found on transferring the unique properties of superstrong individual nanoparticles like carbon nanotubes and graphene nanoplatelets into load bearing engineering materials. After reviewing structure and properties of nano-carbon properties the size effect governing the reduction of inherent mechanical properties upon transfer into macroscopic engineering materials is considered. While the potential of mechanical property enhancement of composites with random orientation of elongated carbon nanoparticles is limited by very low percolation thresholds, manufacturing of aligned microstructures, and tailoring of nanoparticle/matrix interface offers plenty of space for optimizing the mechanical properties of composites subjected to tensile loads. Since compression is the more common loading situation for ultra low-density nano-carbon materials the collapse stress is important for deriving design limits of nanoporous carbon materials. At the same level of density materials with nanotube or sheet carbon allotropes forming the struts may be expected to achieve a compression strength orders of magnitude higher than the porous graphitic materials. Finally, economic aspects of nano-carbon manufacturing are discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA. Source

Kleindienst A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Acta neurochirurgica. Supplement | Year: 2012

Atrial natriuretic peptide (ANP) plays an important role in body fluid homeostasis. ANP has been established as a marker of cardiac dysfunction and may play a role in brain edema development after traumatic brain injury (TBI). In order to identify its specific assignment following TBI, we related clinical data and treatment variables in 63 patients to longitudinal midregional (MR) proatrail natriuretic peptide (ANP) measurements. ANP correlated significantly to age (p < 0.0001) and vasopressin release (p < 0.001). Following TBI, ANP was increased initially and on day 3 (cut-off 100 pg/L) in 22% of the patients, in 31% on day 7, and was normalized at follow-up examination. The group comparison revealed that ANP levels did not significantly differ with regard to injury severity, but that high ANP levels predicted a worse Glasgow Outcome Score at 6 months (p < 0.05). While the initially intact osmoregulation - a correlation of urine volume and high serum sodium (r = 0.536, p = 0.003) or low urine osmolality (r = -0.556, p = 0.009) - got lost post-injury, the ANP release was triggered by volume load (p < 0.005). High ANP levels correlated with the neuroendocrine stress response, i.e., high cortisol (p = 0.05) and prolactin (p < 0.001) levels. We conclude that MR-proANP measurements reveal a significant predictive function for the prognosis of TBI. Source

Zweier M.,Friedrich - Alexander - University, Erlangen - Nuremberg | Rauch A.,University of Zurich
Molecular Syndromology | Year: 2011

Disorders related to the autosomal transcription factor MEF2C located in 5q14.3 were first described in 2009 and have since evolved to one of the more common microdeletion syndromes. Mutational screening in a larger cohort revealed heterozygous de novo mutations of MEF2C in about 1% of patients with moderate to severe intellectual disability, and the phenotype is similar in patients with intragenic deletions and multigenic microdeletions. Clinically, MEF2C-related disorders are characterized by severe intellectual disability with absent speech and limited walking abilities, hypotonia, seizures, and a variety of minor brain anomalies. The majority of patients show a similar facial gestalt with broad forehead, flat nasal bridge, hypotonic mouth, and small chin, as well as strabismus, but this phenotype is clinically not well recognized. The course of the disease is generally quite uniform, but patients with point mutations and smaller deletions seem to have a higher chance of walking skills and a lower risk of refractory seizures. Patients in whom the microdeletion also includes the RASA1 gene show features of the respective capillary and arterio-venous malformations and fistula syndrome. The phenotypic overlap with Rett syndrome is explained by a shared pathway and, accordingly, diminished MECP2 and CDKL5 expression is measureable in patients with MEF2C defects. Further research of this pathway may therefore eventually lead to a common therapeutic target. Copyright © 2012 S. Karger AG, Basel. Source

Schultheiss O.C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Schiepe-Tiska A.,TU Munich
Frontiers in Human Neuroscience | Year: 2013

Implicit motives like the need for power (nPower) scale affective responses to need-specific rewards or punishments and thereby influence activity in motivational-brain structures. In this paper, we review evidence specifically supporting a role of the striatum in nPower. Individual differences in nPower predict (a) enhanced implicit learning accuracy, but not speed, on serial-response tasks that are reinforced by power-related incentives (e.g., winning or losing a contest; dominant or submissive emotional expressions) in behavioral studies and (b) activation of the anterior caudate in response to dominant emotional expressions in brain imaging research. We interpret these findings on the basis of Hikosaka, Nakamura, Sakai, and Nakahara's (2002; Current Opinion in Neurobiology, 12(2), 217-222) model of central mechanisms of motor skill learning. The model assigns a critical role to the dorsoanterior striatum in dopamine-driven learning of spatial stimulus sequences. Based on this model, we suggest that the dorsoanterior striatum is the locus of nPower-dependent reinforcement. However, given the centrality of this structure in a wide range of motivational pursuits, we also propose that activity in the dorsoanterior striatum may not only reflect individual differences in nPower, but also in other implicit motives, like the need for achievement or the need for affiliation, provided that the proper incentives for these motives are present during reinforcement learning. We discuss evidence in support of such a general role of the dorsoanterior striatum in implicit motivation. © 2013 Schultheiss and Schiepe-tiska. Source

Zweier C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Molecular Syndromology | Year: 2011

While heterozygous variants in CNTNAP2 and NRXN1 are reported as susceptibility factors for neuropsychiatric disorders, homozygous or compound heterozygous defects in either gene were reported as causative for severe neurodevelopmental disorders. This review provides an overview of the clinical aspects in patients with recessive defects in CNTNAP2 and NRXN1. Copyright © 2011 S. Karger AG, Basel. Source

Inayat A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Reinhardt B.,University of Leipzig | Uhlig H.,University of Leipzig | Einicke W.-D.,University of Leipzig | Enke D.,University of Leipzig
Chemical Society Reviews | Year: 2013

This review deals with "classical" porous glasses which are prepared by physical phase separation of alkali borosilicate glasses of suitable composition in combination with selective leaching. The resulting materials are characterized by a controllable pore size in the nanometer range, high mechanical, thermal and chemical stability and an adjustable macroscopic shape, which enables manufacturing of glass monoliths with various geometries. As a result of their formation, porous glasses obtained from physical phase separation exhibit a monomodal pore structure. There are only a few examples in the literature for the synthesis of hierarchically porous glasses. This review covers several synthesis strategies for the introduction of hierarchy into "classical" porous glass monoliths, including sintering and fusion of alkali borosilicate initial glasses as well as partial or complete pseudomorphic transformation of porous glasses into zeolites or ordered mesoporous materials. © The Royal Society of Chemistry 2013. Source

Gold R.,Ruhr University Bochum | Linker R.A.,Friedrich - Alexander - University, Erlangen - Nuremberg | Stangel M.,Hannover Medical School
Clinical Immunology | Year: 2012

Fumaric acid was originally therapeutically used in psoriasis. Several lines of evidence have demonstrated immunomodulatory but also neuroprotective effects for FAE. Clinical studies in psoriasis showed a reduction of peripheral CD4+ and CD8+ T-lymphocytes due to the ability of FAE to induce apoptosis. In vitro studies with the ester dimethylfumarate (DMF) described an inhibitory effect on nuclear factor kappa B (NF-κB)-dependent transcription of tumor necrosis factor-alpha (TNF-α) induced genes in human endothelial cells. Animal experiments in the mouse model of central nervous system demyelination, MOG-induced experimental autoimmune encephalomyelitis, revealed a clear preservation of myelin and axonal density in the plaque. Molecular studies showed that this is based on the antioxidative mechanism of action via induction of the transcription factor Nrf-2. A phase II clinical trial in relapsing-remitting multiple sclerosis (RRMS) patients with dimethylfumarate showed a significant reduction in the number of gadolinium enhancing lesions after 24. weeks. © 2011 Elsevier Inc. Source

Wagner C.,Friedrich - Alexander - University, Erlangen - Nuremberg | Hensel M.,University of Osnabruck
Advances in Experimental Medicine and Biology | Year: 2011

Salmonella enterica is an invasive, facultative intracellular pathogen of animal and man with the ability to colonize various niches in diverse host organisms. The pathogenesis of infections by S. enterica requires adhesion to various host cell surfaces, and a large number of adhesive structures can be found. Depending on the serotype of S. enterica, gene clusters for more than 10 different fimbrial adhesins were identified, with type I fimbriae such as Fim, Lpf (long polar fimbriae), Tafi (thin aggregative fimbriae) or the type IV pili of serotype Typhi. In addition, autotransporter adhesins such as ShdA, MisL and SadA and the type I secreted large repetitive adhesins SiiE and BapA have been identified. Although the functions of many of the various adhesins are not well understood, recent studies show the specific structural and functional properties of Salmonella adhesins and how they act in concert with other virulence determinants. In this chapter, we describe the molecular characteristics of Salmonella adhesins and link these features to their multiple functions in infection biology. © 2011 Springer Science+Business Media B.V. Source

Zirlik S.,Friedrich - Alexander - University, Erlangen - Nuremberg
Medical science monitor : international medical journal of experimental and clinical research | Year: 2011

Recent studies suggest that adipose tissue hormones are involved in the pathogenesis of obstructive sleep apnoea syndrome (OSAS). The role of leptin, obestatin and apelin still needs to be established. Ten patients with newly diagnosed OSAS (AHI >10/h and ESS >10 points) were enrolled in the study as well as ten healthy volunteers as controls. All underwent measurements for Leptin, Obestatin and Apelin in four hour intervals during diagnostic polysomnography for 24 h and the patients also three months after onset of CPAP treatment. Furthermore the HOMA-index and body composition were quantified. Plasma apelin levels in the patients decreased under CPAP therapy, but showed no significant difference in patients and volunteers. We found a positive correlation to AHI, BMI in the therapy group at all observation points. Leptin plasma levels were higher in the patient group and decreased after onset of CPAP therapy. Leptin plasma levels were positively correlated to the BMI, min. 02 and AHI in the patient group before therapy. Plasma obestatin levels did not differ significantly in these three observation groups, but were partly correlated to AHI and weight in the newly diagnosed OSAS group. In agreement with previous investigations, we could demonstrate a difference in leptin plasma levels between healthy volunteers and patients with newly diagnosed OSAS. Apelin decreases under CPAP therapy, but not significantly. Obestatin remains unchanged after onset of CPAP. We further found a linkage between leptin plasma levels and BMI, AHI and weight in the untreated patient group. Source

Kisch H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Angewandte Chemie - International Edition | Year: 2013

Preceding work on photoelectrochemistry at semiconductor single-crystal electrodes has formed the basis for the tremendous growth in the three last decades in the field of photocatalysis at semiconductor powders. The reason for this is the unique ability of inorganic semiconductor surfaces to photocatalyze concerted reduction and oxidation reactions of a large variety of electron-donor and -acceptor substrates. Whereas great attention was paid to water splitting and the exhaustive aerobic degradation of pollutants, only a small amount of research also explored synthetic aspects. After introducing the basic mechanistic principles, standard experiments for the preparation and characterization of visible light active photocatalysts as well as the investigation of reaction mechanisms are discussed. Novel atom-economic C-C and C-N coupling reactions illustrate the relevance of semiconductor photocatalysis for organic synthesis, and demonstrate that the multidisciplinary field combines classical photochemistry with electrochemistry, solid-state chemistry, and heterogeneous catalysis. Photoinduced charge generation at semiconductor surfaces is currently the most promising method for the chemical utilization of visible light. These charges can be utilized for catalytic redox processes such as nitrogen fixation, functionalization of alkanes, and linear addition reactions of olefins to 1,2-diazenes and imines. Semiconductor photocatalysis combines aspects of classical photochemistry with electrochemistry, solid-state chemistry, and heterogeneous catalysis. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kappes A.,Friedrich - Alexander - University, Erlangen - Nuremberg
Nuclear and Particle Physics Proceedings | Year: 2015

After a brief introduction to neutrino oscillation, the article discusses how proposed detectors like PINGU and ORCA can use atmospheric neutrinos in the GeV range to determine the neutrino mass hierarchy, one of the crucial unknowns in the neutrino sector of particle physics, and what uncertainties on external input parameters have to be taken into account. © 2015 Elsevier B.V. Source

Tsogoeva S.B.,Friedrich - Alexander - University, Erlangen - Nuremberg
Journal of Systems Chemistry | Year: 2013

Recent reports about enantioselective organoautocatalytic systems, in which small organic molecules assist in their own formation and under conservation of their absolute configuration, are discussed. This process, appearing as a natural extension to non-covalent enantioselective organocatalysis, seems analogous to template-directed self-replication, previously observed in simple organic molecules and holds implications for models on the origin of life. © 2010 Tsogoeva; licensee BioMed Central Ltd. Source

Schett G.,Friedrich - Alexander - University, Erlangen - Nuremberg | Gravallese E.,University of Massachusetts Medical School
Nature Reviews Rheumatology | Year: 2012

Bone erosion is a central feature of rheumatoid arthritis and is associated with disease severity and poor functional outcome. Erosion of periarticular cortical bone, the typical feature observed on plain radiographs in patients with rheumatoid arthritis, results from excessive local bone resorption and inadequate bone formation. The main triggers of articular bone erosion are synovitis, including the production of proinflammatory cytokines and receptor activator of nuclear factor κB ligand (RANKL), as well as antibodies directed against citrullinated proteins. Indeed, both cytokines and autoantibodies stimulate the differentiation of bone-resorbing osteoclasts, thereby stimulating local bone resorption. Although current antirheumatic therapy inhibits both bone erosion and inflammation, repair of existing bone lesions, albeit physiologically feasible, occurs rarely. Lack of repair is due, at least in part, to active suppression of bone formation by proinflammatory cytokines. This Review summarizes the substantial progress that has been made in understanding the pathophysiology of bone erosions and discusses the improvements in the diagnosis, monitoring and treatment of such lesions. © 2012 Macmillan Publishers Limited. All rights reserved. Source

Beyer C.,Friedrich - Alexander - University, Erlangen - Nuremberg
Current rheumatology reports | Year: 2013

The morphogen pathways Wnt, hedgehog, and Notch are key regulators of organ development and tissue homeostasis. In adults, the tightly regulated activity of morphogen pathways is essential for cell renewal and tissue regeneration. Loss of control and persistent activation of morphogen pathways, however, can lead to a variety of diseases, including malignancy and fibrotic disorders. In recent years, pathological activation of Wnt, hedgehog, and Notch pathways have been described in systemic sclerosis (SSc) and other fibrotic diseases. Experimental models reveal that morphogen pathways drive fibroblast activation and collagen release. In these model systems, genetic or pharmacological blockade of morphogen pathways inhibits collagen release and reduces experimental fibrosis. Importantly, inhibitors for Wnt, hedgehog, and Notch are already in clinical evaluation, thereby emphasizing the translational implications of these findings. Further experimental studies, however, should deepen our knowledge before initiating clinical trials with inhibitors of morphogen pathways. Source

Bruns H.,Friedrich - Alexander - University, Erlangen - Nuremberg | Stenger S.,Universitatsklinikum Ulm
Future Microbiology | Year: 2014

Mycobacterium tuberculosis is a facultative intracellular pathogen. It infects macrophages where it avoids elimination by interfering with host defense mechanisms. Until recently, it was assumed that the acidification of phagosomes is the major strategy of macrophages to eliminate M. tuberculosis. However, there is emerging evidence demonstrating that human macrophages are equipped with additional antimicrobial effector functions. Specifically, autophagy, efferocytosis and antimicrobial peptides have been identified as mechanisms to restrict mycobacterial proliferation. Here we review recent findings on effector functions of human macrophages and mechanisms of the pathogen to interfere with them. © 2014 Future Medicine Ltd. Source

Navalpakkam B.K.,Pattern Recognition Laboratory | Navalpakkam B.K.,Institute of Medical Physics | Braun H.,Institute of Medical Physics | Kuwert T.,Friedrich - Alexander - University, Erlangen - Nuremberg | Quick H.H.,Institute of Medical Physics
Investigative Radiology | Year: 2013

OBJECTIVES: Attenuation correction of positron emission tomographic (PET) data is critical in providing accurate and quantitative PET volumes. Deriving an attenuation map (μ-map) from magnetic resonance (MR) volumes is a challenge in PET/MR hybrid imaging. The difficulty lies in differentiating cortical bone from air from standard MR sequences because both these classes yield little to no MR signal and thus shows no distinguishable information. The objective of this contribution is 2-fold: (1) to generate and evaluate a continuous valued computed tomography (CT)-like attenuation map (μ-map) with continuous density values from dedicated MR sequences and (2) to compare its PET quantification accuracy with respect to a CT-based attenuation map as the criterion standard and other segmentation-based attenuation maps for studies of the head. MATERIALS AND METHODS: Three-dimensional Dixon-volume interpolated breath-hold examination and ultrashort echo time sequences were acquired for each patient on a Siemens 3-T Biograph mMR PET/MR hybrid system and the corresponding patient CT on a Siemens Biograph 64. A pseudo-CT training was done using the epsilon-insensitive support vector regression ([Latin Small Letter Open E]-SVR) technique on 5 patients who had CT/MR/PET triplets, and the generated model was evaluated on 5 additional patients who were not included in the training process. Four μ-maps were compared, and 3 of them derived from CT: scaled CT (μ-mapCT), 3-class segmented CT without cortical bone (μ-mapnobone), 4-class segmented CT with cortical bone (μ-mapbone), and 1 from MR sequences via [Latin Small Letter Open E]-SVR technique previously mentioned (ie, MR predicted [μ-mapMR]). Positron emission tomographic volumes with each of the previously mentioned μ-maps were reconstructed, and relative difference images were calculated with respect to μ-mapCT as the criterion standard. RESULTS: For PET quantification, the proposed method yields a mean (SD) absolute error of 2.40% (3.69%) and 2.16% (1.77%) for the complete brain and the regions close to the cortical bone, respectively. In contrast, PET using μ-mapnobone yielded 10.15% (3.31%) and 11.03 (2.26%) for the same, although PET using μ-mapbone resulted in errors of 3.96% (3.71%) and 4.22% (3.91%). Furthermore, it is shown that the model can be extended to predict pseudo-CTs for other anatomical regions on the basis of only MR information. CONCLUSIONS: In this study, the generation of continuous valued attenuation maps from MR sequences is demonstrated and its effect on PET quantification is evaluated in comparison with segmentation-based μ-maps. A less-than-2-minute acquisition time makes the proposed approach promising for a clinical application for studies of the head. However, further experiments are required to validate and evaluate this technique for attenuation correction in other regions of the body. Copyright © 2013 by Lippincott Williams & Wilkins. Source

Mughrabi H.,Friedrich - Alexander - University, Erlangen - Nuremberg
Philosophical Transactions of the Royal Society A: Mathematical, Physical and Engineering Sciences | Year: 2015

In this survey, the origin of fatigue crack initiation and damage evolution in different metallic materials is discussed with emphasis on the responsible microstructural mechanisms. After a historical introduction, the stages of cyclic deformation which precede the onset of fatigue damage are reviewed. Different types of cyclic slip irreversibilities in the bulk that eventually lead to the initiation of fatigue cracks are discussed. Examples of trans- and intercrystalline fatigue damage evolution in the low cycle, high cycle and ultrahigh cycle fatigue regimes in mono- and polycrystalline face-centred cubic and body-centred cubic metals and alloys and in different engineering materials are presented, and some microstructural models of fatigue crack initiation and early crack growth are discussed. The basic difficulties in defining the transition from the initiation to the growth of fatigue cracks are emphasized. In ultrahigh cycle fatigue at very low loading amplitudes, the initiation of fatigue cracks generally occupies a major fraction of fatigue life and is hence life controlling. © 2015 The Author(s) Published by the Royal Society. All rights reserved.