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Frankfurt am Main, Germany

The Goethe University Frankfurt is a university which was founded in 1914 as a Citizens' University, which means that, while it was a State university of Prussia, it had been founded and financed by the wealthy and active liberal citizenry of Frankfurt am Main, a unique feature in German university history. It was named in 1932 after one of the most famous natives of Frankfurt, the poet and writer Johann Wolfgang von Goethe. Today, the university has 46,000 students, on 4 major campuses within the city.Several Nobel Prize winners have been affiliated with the university, such as Max von Laue. The university is also affiliated with 11 winners of the Gottfried Wilhelm Leibniz Prize. Wikipedia.


Muller I.,Goethe University Frankfurt
Clinical & developmental immunology | Year: 2012

Data on the economic impact of Lyme borreliosis (LB) on European health care systems is scarce. This project focused on the epidemiology and costs for laboratory testing in LB patients in Germany. We performed a sentinel analysis of epidemiological and medicoeconomic data for 2007 and 2008. Data was provided by a German statutory health insurance (DAK) company covering approx. 6.04 million members. In addition, the quality of diagnostic testing for LB in Germany was studied. In 2007 and 2008, the incident diagnosis LB was coded on average for 15,742 out of 6.04 million insured members (0.26%). 20,986 EIAs and 12,558 immunoblots were ordered annually for these patients. For all insured members in the outpatient sector, a total of 174,820 EIAs and 52,280 immunoblots were reimbursed annually to health care providers (cost: 2,600,850€). For Germany, the overall expected cost is estimated at 51,215,105€. However, proficiency testing data questioned test quality and standardization of diagnostic assays used. Findings from this study suggest ongoing issues related to care for LB and may help to improve future LB disease management. Source


Ehrnstorfer I.A.,University of Zurich | Geertsma E.R.,University of Zurich | Geertsma E.R.,Goethe University Frankfurt | Pardon E.,Structural biology research center | And 4 more authors.
Nature Structural and Molecular Biology | Year: 2014

Members of the SLC11 (NRAMP) family transport iron and other transition-metal ions across cellular membranes. These membrane proteins are present in all kingdoms of life with a high degree of sequence conservation. To gain insight into the determinants of ion selectivity, we have determined the crystal structure of Staphylococcus capitis DMT (ScaDMT), a close prokaryotic homolog of the family. ScaDMT shows a familiar architecture that was previously identified in the amino acid permease LeuT. The protein adopts an inward-facing conformation with a substrate-binding site located in the center of the transporter. This site is composed of conserved residues, which coordinate Mn 2+, Fe 2+ and Cd 2+ but not Ca 2+. Mutations of interacting residues affect ion binding and transport in both ScaDMT and human DMT1. Our study thus reveals a conserved mechanism for transition-metal ion selectivity within the SLC11 family. Source


Fulda S.,Goethe University Frankfurt
Methods in Enzymology | Year: 2014

Accumulating evidence indicates that metabolism plays a critical role in the control of various cellular functions, including cell death. Thus, several mechanisms of programmed cell death have been shown to be controlled by metabolic cues. Since programmed cell death represents a fundamental process in various physiological and pathophysiological conditions, including oncogenesis, tumor progression, and resistance to therapy, the metabolic profile of cancer cells is expected to have a significant impact on all these phases of malignant transformation. Further insights into the signal transduction cascades that regulate different cell death pathways in response to metabolic fluctuations will likely result in the identification of potential targets for the development of novel therapeutic interventions. As the deregulation of cell metabolism as well as alterations in cell death pathways are involved in the pathogenesis of multiple human diseases other than cancer, this knowledge has a great translational potential in several areas of medicine. © 2014 Elsevier Inc. All rights reserved. Source


Zlatkin O.,Hebrew University of Jerusalem | Avigad D.,Hebrew University of Jerusalem | Gerdes A.,Goethe University Frankfurt | Gerdes A.,Stellenbosch University
Gondwana Research | Year: 2013

In the Menderes Massif (western Taurides) a Neoproterozoic basement comprising metasediments and intrusive granites is imbricated between Paleozoic platform sediments. U-Pb-Hf zircon analyses of Menderes rock units were performed by us using LA-ICP-MS. The U-Pb detrital zircon signal of the Neoproterozoic metasediments is largely consistent with a NE African (Gondwana) provenance. The oldest unit, a paragneiss, contains significant amounts (~. 30%) of Archean-aged zircons and εHf (t) values of about a half of its Neoproterozoic zircons are negative suggesting contribution from Pan-African terranes dominated by reworking of an old crust. In the overlying, mineralogically-immature Core schist (which is still Neoproterozoic), the majority of the detrital zircons are Neoproterozoic, portraying positive εHf (t) values indicating derivation from a proximal juvenile source, resembling the Arabian-Nubian Shield. The period of sedimentation of the analyzed metasediments, is constrained between 570 and 550Ma (Late Ediacaran). The Core schist sediments, ~9km thick, accumulated in less than 20My implying a tectonic-controlled sedimentary basin evolved adjacent to the eroded juvenile terrane. Granites, now orthogneisses, intruded the basin fill at 550Ma, they exhibit ±0 εHf (t=550Ma) and TDM ages of 1.4Ga consistent with anatexis of various admixtures of juvenile Neoproterozoic and Late Archean detrital components. Granites in the northern Arabian-Nubian Shield are no younger than 580Ma and their εHf (t) are usually more positive. This implies that the Menderes does not represent a straightforward continuation of the Arabian-Nubian Shield. The lower part of the pre-Carboniferous silisiclastic cover of the Menderes basement, comprises a yellowish quartzite whose U-Pb-Hf detrital zircon signal resembles that of far-traveled Ordovician sandstones in Jordan (including 0.9-1.1. Ga detrital zircons), supporting pre-Triassic paleorestorations placing the Tauride with Afro-Arabia. The detrital signal of the overlying carbonate-bearing quartzitic sequence indicates contribution from a different source: the majority of its detrital zircons yielded 550. Ma and ± 0 εHf (t = 550. Ma) values identical to that of the underlying granitic gneiss implying exposure of Menderes-like granites in the provenance.260-250. Ma lead-loss and partial resetting of the U-Pb system of certain zircons in both basement and cover units was detected. It is interpreted as a consequence of a Permian-Early Triassic thermal event preceding known Triassic granitoid intrusions. © 2012 International Association for Gondwana Research. Source


Soppa J.,Goethe University Frankfurt
Biochemical Society Transactions | Year: 2011

The genome copy numbers of seven crenarchaeal species of four genera have been reported. All of them are monoploid and thus this seems to be a characteristic feature of Crenarchaeota. In stark contrast, none of six species representing six euryarchaeal genera is monoploid. Therefore Euryarchaea are typically oligoploid or polyploidy and their genome copy numbers are tightly regulated in response to growth phase and/or growth rate. A theoretical consideration called 'Muller's ratchet' predicts that asexually reproducing polyploid species should not be able to exist. An escape from Muller's ratchet would be a mechanism leading to the equalization of genome copies, such as gene conversion. Using two species of methanogenic and halophilic archaea, it was shown that heterozygous cells containing different genomes simultaneously can be selected, exemplifying gene redundancy as one possible evolutionary advantage of polyploidy. In both cases, the genomes were rapidly equalized in the absence of selection, showing that gene conversion operates at least in halophilic and methanogenic Euryarchaea. ©The Authors Journal compilation ©2011 Biochemical Society. Source


Koch J.,Paul Ehrlich Institute | Steinle A.,Goethe University Frankfurt | Watzl C.,Leibniz Research Center for Working Environment and Human Factors o | Mandelboim O.,Hebrew University of Jerusalem
Trends in Immunology | Year: 2013

Natural killer (NK) cells are central players in the vertebrate immune system that rapidly eliminate malignantly transformed or infected cells. The natural cytotoxicity receptors (NCRs) NKp30, NKp44, and NKp46 are important mediators of NK cell cytotoxicity, which trigger an immune response on recognition of cognate cellular and viral ligands. Tumour and viral immune escape strategies targeting these receptor-ligand systems impair NK cell cytotoxicity and promote disease. Therefore, a molecular understanding of the function of the NCRs in immunosurveillance is instrumental to discovering novel access points to combat infections and cancer. © 2013 Elsevier Ltd. Source


Meissner M.,Goethe University Frankfurt
Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG | Year: 2012

Fumaric acid esters have been used successfully in the therapy of psoriasis vulgaris since 1959. In the last 17 years, many of the underlying mechanisms of anti-psoriatic action, such as a Th1/Th2 shift, a suppression of important leukocyte adhesion molecules, the induction of pro-apoptotic pathways in T-cells and recently anti-angiogenic action, have been discovered. Based on the knowledge of these immunomodulatory characteristics, fumaric acid esters have been shown to be effective or potentially effective in a multitude of dermatological as well as non-dermatological diseases. The range of new therapeutic targets reaches from multiple sclerosis to illnesses such as necrobiosis lipoidica, granuloma annulare and sarcoidosis. Experimental approaches offer promising, although preliminary, results on the treatment of cancer, malaria, chronic inflammatory lung diseases, and Huntington disease, to name but a few. This valued and well-known drug mainly prescribed by dermatologists is now experiencing a renaissance far beyond dermatologic applications. © The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin. Source


Yang M.,Huazhong University of Science and Technology | Kloeden P.E.,Goethe University Frankfurt
Nonlinear Analysis: Real World Applications | Year: 2011

The existence of a random attractor is established for a class of stochastic semi-linear degenerate parabolic equations with the leading term of the form div(σ(x)∇u) and additive spatially distributed temporal noise. The nonlinearity is dissipative for large values of the state without restriction on the growth order of the polynomial, while the spatial domain is either bounded or unbounded. © 2011 Elsevier Ltd. All rights reserved. Source


Rosol M.,Goethe University Frankfurt
International Journal of Urban and Regional Research | Year: 2010

This article examines citizen participation in the governance of contemporary urban green space. Rather than exploring normative questions of ideal forms of participatory democracy, it focuses on changing roles and relationships between local state and non-state actors in order to identify and explain the changing nature of participation. I argue that neoliberal urban restructuring has changed the conditions for participation and thus participation itself in fundamental ways and that we need an account of changes in statehood and governance in order to capture this conceptually. Based on the case of community gardens in Berlin, the article discusses the extent to which this changed relationship is expressed by current citizen participation as well as the potential and problems that result from it. My empirical results show the emergence of a new political acceptance of autonomously organized projects and active citizen participation in urban green space governance. The central argument of this article is that this new acceptance can be conceptualized as an expression of the neoliberalization of cities. Nevertheless, this neoliberal strategy at the same time leads to complex and contradictory outcomes and the resulting benefits are also acknowledged. © 2010 The Author. International Journal of Urban and Regional Research © 2010 Joint Editors and Blackwell Publishing Ltd. Source


Doerr H.W.,Goethe University Frankfurt
Medical Microbiology and Immunology | Year: 2013

Since 1995, many countries have been aiming to replace the natural immunity against varicella by a vaccine-induced immunity to protect against varicella and herpes zoster. While the frequency of varicella in childhood has been significantly reduced, in future, herpes zoster morbidity might increase in the elderly due to the weaker immunity post-vaccination and the absence of immunity boosting silent reinfections. In countries, where less than 90 % of children are covered by universal vaccination, varicella zoster virus (VZV) infection is not completely eradicated, but might move from childhood to the age of young adults who suffer from more serious complications. A special VZV vaccine against herpes zoster in adults aged >60 years has proven to be effective in many cases, but not all vaccinees. This might lead to problems regarding the acceptance of vaccination and delay rapid antiviral therapy to prevent the post-zosteric neuralgia. An efficacious-inactivated VZV vaccine to protect immunocompromised patients is still missing. VZV vaccines and vaccination strategies have to be optimised to avoid that the quality of life and cost savings from varicella reduction in childhood are offset by more VZV diseases in adults. © 2013 Springer-Verlag Berlin Heidelberg. Source


Muller B.,University of Heidelberg | Heilemann M.,Goethe University Frankfurt | Heilemann M.,University of Heidelberg
Trends in Microbiology | Year: 2013

For more than 70 years electron microscopy (EM) techniques have played an important role in investigating structures of enveloped viruses. By contrast, use of fluorescence microscopy (FM) methods for this purpose was limited by the fact that the size of virus particles is generally around or below the diffraction limit of light microscopy. Various super-resolution (SR) fluorescence imaging techniques developed over the past two decades bypass the diffraction limit of light microscopy, allowing visualization of subviral details and bridging the gap between conventional FM and EM methods. We summarize here findings on human immunodeficiency virus (HIV-1) obtained using SR-FM techniques. Although the number of published studies is currently limited and some of the pioneering analyses also covered methodological or descriptive aspects, recent publications clearly indicate the potential to approach open questions in HIV-1 replication from a new angle. © 2013 Elsevier Ltd. Source


Fulda S.,Goethe University Frankfurt
Klinische Padiatrie | Year: 2010

One of the hallmarks of human cancers is the deregulation of signal transduction pathways that regulate fundamental processes such as cell proliferation and cell death. This leads to the disturbance in the physiological control of tissue homeostasis and a concomitant net increase in cell number. Thus, deregulation of intracellular signaling events can contribute to tumorigenesis and tumor progression. In addition, this may also confer treatment resistance, since the response of cancer cells towards most cytotoxic therapies including chemo-, radio- or immunotherapy critically depends on intact signaling cascades that eventually lead to cell death. Hence, a better understanding of the molecular mechanisms that regulate cell death and survival programs in cancer cells is expected to provide the basis for the development of new diagnostic and therapeutic strategies. © Georg Thieme Verlag KG Stuttgart New York. Source


The use of selective antegrade cerebral perfusion (ACP) makes deep hypothermia nonessential for aortic arch replacement. Consequently, a growing tendency to increase the body temperature during circulatory arrest with ACP has recently been reported from various institutions. However, very little is known about the clinical effect of different modes of ACP (unilateral vs bilateral) on neurologic morbidity. Also, the safe limits of this approach for spinal chord and visceral organ protection are yet to be defined. Between January 2000 and January 2011, 1002 consecutive patients underwent aortic arch repair during ACP (unilateral, 673; bilateral, 329) with mild systemic hypothermia (30°C ± 2°C; range, 26°-34°C) at 2 centers in Germany. The mean patient age was 62 ± 14 years, 663 patients (66%) were men, and 347 patients (35%) had acute type A dissection. Hemiarch replacement was performed in 684 patients (68%), and 318 (32%) underwent total arch replacement. The cardiopulmonary bypass time accounted for 158 ± 56 minutes and the myocardial ischemic time, 101 ± 41 minutes. Isolated ACP was performed for 36 ± 19 minutes (range, 9-135). We observed new postoperative permanent neurologic deficits in 28 patients (3%; stroke in 25 and paraplegia in 3) and transient neurologic deficits in 42 patients (4%). All 3 cases of paraplegia occurred in patients with acute type A dissection and a broad range of ACP times (24, 41, and 127 minutes). A trend was seen toward a reduced permanent neurologic deficit rate after unilateral ACP (P = .06), but no difference was seen in the occurrence of transient neurologic deficits (P = .6). Overall, the early mortality rate was 5% (n = 52). Temporary dialysis was necessary primarily after surgery in 38 patients (4%). When corrected for the unequal distribution of type A dissection, neurologic morbidity, early mortality, and the need for temporary dialysis were independent of the duration of ACP and were not affected by unilateral versus bilateral ACP. Current data suggest that ACP and mild systemic hypothermic circulatory arrest can be safely applied to complex aortic arch surgery even in a subgroup of patients with up to 90 minutes of ACP. Unilateral ACP offers at least equal brain and visceral organ protection as bilateral ACP and might be advantageous in that it reduces the incidence of embolism arising from surgical manipulation on the arch vessels. Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved. Source


Hippolyte B.,CNRS Hubert Curien Multi-disciplinary Institute | Rischke D.H.,Goethe University Frankfurt
Nuclear Physics A | Year: 2013

In these proceedings, we highlight recent developments from both theory and experiment related to the global description of matter produced in ultra-relativistic heavy-ion collisions as presented during the Quark Matter 2012 conference. © 2013 Elsevier B.V. Source


Sahlmueller B.,Goethe University Frankfurt
Nuclear Physics A | Year: 2013

To interpret the measurements in heavy-ion collisions at the Relativistic Heavy-Ion Collider (RHIC) it is crucial to understand the initial state of the colliding gold (Au) nuclei. The parton distribution in Au nuclei is modified compared to protons, and their isospin composition is different due to the presence of neutrons. d + Au collisions at RHIC at the same collision energies are an important tool to study initial state modifications. PHENIX has measured π0, η, and reconstructed jets at high transverse momentum. These data are compared to predictions from nuclear parton distribution functions. Furthermore, single electrons from heavy-flavor decays have been measured by PHENIX. © 2013 Elsevier B.V. Source


Riesch R.,University of Oklahoma | Plath M.,Goethe University Frankfurt | Schlupp I.,University of Oklahoma
Ecology | Year: 2010

Life-history traits are very sensitive to extreme environmental conditions, because resources that need to be invested in somatic maintenance cannot be invested in reproduction. Here we examined female life-history traits in the Mexican livebearing fish Poecilia mexicana from a variety of benign surface habitats, a creek with naturally occurring toxic hydrogen sulfide (H 2S), a sulfidic cave, and a non-sulfidic cave. Previous studies revealed pronounced genetic and morphological divergence over very small geographic scales in this system, despite the absence of physical barriers, suggesting that local adaptation to different combinations of two selection factors, toxicity (H2S) and darkness, is accompanied by very low rates of gene flow. Hence, we investigated life-history divergence between these populations in response to the selective pressures of darkness and/or toxicity. Our main results show that toxicity and darkness both select for (or impose constraints on) the same female trait dynamics: reduced fecundity and increased offspring size. Since reduced fecundity in the sulfur cave population was previously shown to be heritable, we discuss how divergent life-history evolution may promote further ecological divergence: for example, reduced fecundity and increased offspring autonomy are clearly beneficial in extreme environments, but fish with these traits are outcompeted in benign habitats. © 2010 by the Ecological Society of America. Source


Fried M.W.,University of North Carolina at Chapel Hill | Hadziyannis S.J.,Henry Dunant Hospital | Shiffman M.L.,Health News | Messinger D.,IST | Zeuzem S.,Goethe University Frankfurt
Journal of Hepatology | Year: 2011

Background & Aims: The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR. Methods: A retrospective analysis of 1383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin, was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis. Results: RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors. Conclusions: Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies. © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source


Biswas M.,Goethe University Frankfurt | Langowski J.,German Cancer Research Center | Bishop T.C.,Louisiana Tech University
Wiley Interdisciplinary Reviews: Computational Molecular Science | Year: 2013

Nearly a dozen all-atom molecular dynamics (MD) simulations of the nucleosome have been performed. Collectively, these simulations provide insights into the structure and dynamics of the biomolecular complex that serves as the fundamental folding unit of chromatin. Nucleosomes contain 146 base pairs of DNA wrapped in a left-handed superhelix around a core of eight histones. This review provides a survey of what has been learned about DNA, histones, and solvent interactions based on all-atom MD studies of the nucleosome. The longest simulations to date are on the order of 100 nanoseconds. On this time scale, nucleosomes are quite stable. DNA kinks, the histone tails, solvent, and ions are highly dynamic and can be readily investigated using equilibrium dynamics methods. Steered MD is required to observe large-scale structural changes. The need for explicit solvent techniques is underscored by the inability of continuum solvent methods to properly describe the ion-nucleosome radial distribution functions. The atomistic techniques reviewed here are deemed necessary for exploration of the near infinite variations in atomic composition that exists even in the canonical nucleosome octamer. Continued development of these nascent simulation efforts will enable experimentalists to utilize rational design strategies in their efforts to investigate nucleosomes and chromatin. © 2013 John Wiley & Sons, Ltd. Source


Coja-Oghlan A.,Goethe University Frankfurt
Electronic Journal of Combinatorics | Year: 2013

Let G(n, m) be the random graph on n vertices with m edges. Let d=2m/n be its average degree. We prove that G(n, m) fails to be k-colorable with high probability if d>2k ln k-ln k-1+ok(1). This matches a conjecture put forward on the basis of sophisticated but non-rigorous statistical physics ideas (Krzakala, Pagnani, Weigt: Phys. Rev. E 70 (2004)). The proof is based on applying the first moment method to the number of "covers", a physics-inspired concept. By comparison, a standard first moment over the number of k-colorings shows that G(n, m) is not k-colorable with high probability if d > 2k ln k - ln k. Source


Freydenberger D.D.,Goethe University Frankfurt
Theory of Computing Systems | Year: 2013

Most modern implementations of regular expression engines allow the use of variables (also called backreferences). The resulting extended regular expressions (which, in the literature, are also called practical regular expressions, rewbr, or regex) are able to express non-regular languages. The present paper demonstrates that extended regular-expressions cannot be minimized effectively (neither with respect to length, nor number of variables), and that the tradeoff in size between extended and "classical" regular expressions is not bounded by any recursive function. In addition to this, we prove the undecidability of several decision problems (universality, regularity, and cofiniteness) for extended regular expressions. Furthermore, we show that all these results hold even if the extended regular expressions contain only a single variable. © 2012 Springer Science+Business Media, LLC. Source


Dietrich C.F.,Innere Medizin 2 | Bojunga J.,Goethe University Frankfurt
Zeitschrift fur Gastroenterologie | Year: 2015

Thyroid nodules and thyroid abnormalities are common findings in the general population. Ultrasonography is the most important imaging tool for diagnosing thyroid disease. In the majority of cases a correct diagnosis can already be made in synopsis of the sonographic together with clinical findings and basal thyroid hormone parameters and an appropriate therapy can be initiated thereafter. A differentiation of hormonally active versus inactive nodes, and in particular benign versus malignant nodules is sonographically, however, not reliably possible. In this context, radioscanning has its clinical significance predominantly in diagnosing hormonal activity of thyroid nodules. Efforts of the past years aimed to improve sonographic risk stratification to predict malignancy of thyroid nodules through standardized diagnostic assessment of evaluated risk factors in order to select patients, who need further diagnostic work up. According to the "Breast Imaging Reporting and Data System" (BI-RADS), "Thyroid Imaging Reporting and Data Systems" (TI-RADS) giving standardized categories with rates of malignancy were evaluated as a basis for further clinical management. Recent technological developments, such as elastography, also show promising data and could gain entrance into clinical practice. The ultrasound-guided fine-needle aspiration is the key element in the diagnosis of sonographically suspicious thyroid nodules and significantly contributes to the diagnosis of malignancy versus benignity. © Georg Thieme Verlag KG. Source


Fulda S.,Goethe University Frankfurt | Fulda S.,German Cancer Research Center
Clinical Cancer Research | Year: 2015

Inhibitor of Apoptosis (IAP) proteins block programmed cell death and are expressed at high levels in various human cancers, thus making them attractive targets for cancer drug development. Second mitochondrial activator of caspases (Smac) mimetics are small-molecule inhibitors that mimic Smac, an endogenous antagonist of IAP proteins. Preclinical studies have shown that Smac mimetics can directly trigger cancer cell death or, even more importantly, sensitize tumor cells for various cytotoxic therapies, including conventional chemotherapy, radiotherapy, or novel agents. Currently, several Smac mimetics are under evaluation in early clinical trials as monotherapy or in rational combinations (i.e., GDC-0917/CUDC-427, LCL161, AT-406/Debio1143, HGS1029, and TL32711/birinapant). This review discusses the promise as well as some challenges at the translational interface of exploiting Smac mimetics as cancer therapeutics. © 2015 American Association for Cancer Research. Source


There is increasing awareness that psoriasis is more than "skin deep." Several recent reviews focused on biomarkers have indicated the systemic dimension of psoriasis and the comorbidity that psoriasis shares with other chronic inflammatory diseases. Of emerging significance is the relationship to cardiovascular disease, which contributes substantially to patients' increased mortality. This article examines currently available evidence favoring the concept of a causal link between psoriasis and cardiovascular disease, and summarizes a report represented at the 2010 Annual Meeting of GRAPPA (Group for Research and Assessment of Psoriasis and Psoriatic Arthritis). The Journal of Rheumatology Copyright © 2012. All rights reserved. Source


Wiseman C.L.S.,University of Toronto | Zereini F.,Goethe University Frankfurt
Atmospheric Environment | Year: 2014

The purpose of this study is to assess the solubility of traffic-related metal(loid)s associated with airborne PM of human health concern, employing a physiologically-based extraction test with simulated lung fluids (artificial lysosomal fluid (ALF) and Gamble's solution). Airborne PM (PM10, PM2.5 and PM1) samples were collected in Frankfurt am Main, Germany, using a high volume sampler. Following extraction of the soluble metal(loid) fractions, sample filters were digested with a high pressure asher. Metal(loid) concentrations (As, Ce, Co, Cr, Cu, Mn, Ni, Pb, Sb, Ti and V) were determined in extracts and digests per ICP-Q-MS.All metal(loid)s occurred at detectable concentrations in the three airborne PM fractions. Copper was the most abundant element in mass terms, with mean concentrations of 105 and 53ng/m3 in PM10 and PM2.5, respectively. Many of the metal(loid)s were observed to be soluble in simulated lung fluids, with Cu, As, V and Sb demonstrating the highest overall mobility in airborne PM. For instance, all four elements associated with PM10 had a solubility of >80% in ALF (24h). Clearly, solubility is strongly pH dependent, as reflected by the higher relative mobility of samples extracted with the acidic ALF.Given their demonstrated solubility, this study provides indirect evidence that a number of toxic metal(loid)s are likely to possess an enhanced pulmonary toxic potential upon their inhalation. The co-presence of many toxic elements of concern in airborne PM suggests an assessment of health risk must consider the possible interactive impacts of multi-element exposures. © 2014 Elsevier Ltd. Source


Mayerhofer P.U.,Goethe University Frankfurt
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2015

The importance of peroxisomes is highlighted by severe inherited human disorders linked to impaired peroxisomal biogenesis. Besides the simple architecture of these ubiquitous and dynamic organelles, their biogenesis is surprisingly complex and involves specialized proteins, termed peroxins, which mediate targeting and insertion of peroxisomal membrane proteins (PMPs) into the peroxisomal bilayer, and the import of soluble proteins into the protein-dense matrix of the organelle. The long-standing paradigm that all peroxisomal proteins are imported directly into preexisting peroxisomes has been challenged by the detection of PMPs inside the endoplasmic reticulum (ER). New models propose that the ER originates peroxisomal biogenesis by mediating PMP trafficking to the peroxisomes via budding vesicles. However, the relative contribution of this ER-derived pathway to the total peroxisome population in vivo, and the detailed mechanisms of ER entry and exit of PMPs are controversially discussed. This review aims to summarize present knowledge about how PMPs are targeted to the ER, instead of being inserted directly into preexisting peroxisomes. Moreover, molecular mechanisms that facilitate bilayer insertion of PMPs among different species are discussed. © 2015 Elsevier B.V. Source


Huth M.,Goethe University Frankfurt
Journal of Applied Physics | Year: 2010

An analysis scheme is presented that allows for a quantitative description of the sensitivity of granular metal based strain sensors. The scheme draws on recent advances in the understanding of charge transport mechanisms in granular metals. How to deduct the relevant model parameters from temperature-dependent conductivity measurements is demonstrated by using recently published data for fcc-packed gold nanoparticle multilayers. Based on this model parameter set the intrinsic strain gauge factor is calculated as function of the intergrain coupling strength for different transport regimes. General trends for strain gauge factor optimization are identified. The absolute values for the calculated gauge factor are in good correspondence with typical values obtained for metal-containing diamondlike carbon thin film strain sensors. © 2010 American Institute of Physics. Source


Uibel S.,Goethe University Frankfurt
Annals of the New York Academy of Sciences | Year: 2012

In 2005, the pianist and conductor Daniel Barenboim initiated the Musikkindergarten Berlin as the first kindergarten in which music is not only used as an occasional add-on but as the central education medium for the child every day. The skills of specially trained kindergarten teachers combined with regular visits by professional musicians of the Staatskapelle Berlin (the Berlin State Opera orchestra) form the basis of a new educational concept, in which children experience music in all its different aspects and in its unique capability as a transfer medium into all the other educational areas. In this context, the method, the aim, and the experimental ground is not only education in or with music, but through music. This paper provides information and examples about first-hand experiences over the last six years. © 2012 New York Academy of Sciences. Source


Arora A.,Goethe University Frankfurt
RNA biology | Year: 2011

We have identified a conserved G-quadruplex forming sequence in the 3' untranslated region (UTR) of the proto-oncogene PIM1. Circular dichroism and thermal denaturation studies revealed that the PIM1 mRNA guanine-rich sequence forms a highly stable intramolecular G-quadruplex structure. Reporter gene assay demonstrated that the PIM1 RNA G-quadruplex represses translation. It is the first experimental evidence of an RNA G-quadruplex structure located in the 3' UTR that may act as posttranscriptional regulator. Source


Baer P.C.,Goethe University Frankfurt
Stem Cells and Development | Year: 2011

Adipose-derived stem cells (ASCs) possess a multilineage differentiation potential, can be used from an autologous origin, and are, therefore, attractive candidates for clinical applications to repair or regenerate damaged tissues and organs. Adipose tissue as a stem cell source is ubiquitously available and has several advantages compared with other sources. It is easily accessible in large quantities with a minimal invasive harvesting procedure, and the isolation of ASCs yields a high amount of stem cells, which is essential for stem cell-based therapies and tissue engineering. Differentiation of ASCs into cell types of mesodermal origin has been shown in a variety of studies. The plasticity of ASCs toward cells of the mesodermal lineage has been shown by their differentiation into chondrocytes, osteoblasts, adipocytes, and myocytes. Their potential to differentiate into lineages with nonmesodermal origin is even more exciting: ASCs are also able to differentiate into cells of ecto- and endodermal origin. Various in vitro and in vivo studies documented the induced differentiation into neural cells, hepatocytes, pancreatic islet cells, endothelial cells, and epithelial cells. Epithelial cells can embryologically arise from each of the 3 germ layers. This article summarizes and discusses the current knowledge of the potential of ASCs to differentiate into the epithelial lineage. The differentiation of ASCs into different types of epithelial cells, including hepatocytes, pancreatic cells, and endothelial cells, is highlighted together with a view on current clinical trials and future options. © Copyright 2011, Mary Ann Liebert, Inc. Source


Autistic Disorders (AD) are characterized by impairments in social interaction and communication, as well as by stereotyped behaviors and interests. Early intervention programs in AD aim to improve several aspects of the child's abilities: joint attention, play abilities, language development, and especially social interaction and communication. In this review article based on a selective literature search, the relatively best empirically based early intervention programs will be discussed with a focus on the proven efficacy of these interventions. © 2010 by Verlag Hans Huber, Hogrefe AG. Source


Schroder K.,Goethe University Frankfurt
Cellular and Molecular Life Sciences | Year: 2014

Bone formation and degradation are perfectly coordinated. In case of an imbalance of these processes diseases occur associated with exaggerated formation of new bone or bone loss as in osteoporosis. Most studies investigating osteoporosis either focus on osteoblast or osteoclast function and differentiation. Both processes have been suggested to be affected by reactive oxygen species (ROS). Besides a potentially harmful role of ROS, these small molecules are important second messengers. The family of NADPH oxidases produces ROS in a controlled and targeted manner, to specifically regulate signal transduction. This review will highlight the role of reactive oxygen species in bone cell differentiation and bone-loss associated disease with a special focus on osteoporosis and NADPH oxidases as specialized sources of ROS. © 2014 Springer Basel. Source


Gischler E.,Goethe University Frankfurt
Palaios | Year: 2010

An analysis of five Holocene sediment cores from Belize atoll lagoons has revealed a possible mass mortality of the Caribbean sea urchins Diadema antillarum and Echinometra sp. during 6400-6100, 4000, and 1300 yr BP. Event layers were identified by quantifying echinoid fragments in Holocene sediments. Peaks of echinoid abundance were dated radiometrically. There are two explanations for the fact that echinoderm-rich layers cannot be correlated among the three atoll lagoons. First, die out was not as widespread as the 1983-84 event that led to mass mortality of Diadema in the Caribbean. Possibly, local environmental transitions in lagoonal circulation patterns and changes in temperature and precipitation in the study area were responsible for echinoid mass mortality in the Holocene of Belize. Second, echinoid mass mortality is not necessarily implied in the composition of contemporaneous reef sediments. Comparable studies on Holocene corals in the area also suggest that turnover events have repeatedly occurred during the past several thousand years, however, recent events were unprecedented in their significance. Potential limitations of this study refer to taphonomic bias as imposed by callianassid shrimp burrowing. © 2010 SEPM (Society for Sedimentary Geology). Source


Kober M.,Goethe University Frankfurt
International Journal of Modern Physics A | Year: 2011

According to the introduction of a minimal length to quantum field theory, which is directly related to a generalized uncertainty principle, the implementation of the gauge principle becomes much more intricated. It has been shown in another paper how gauge theories have to be extended in general, if there is assumed the existence of a minimal length. In this paper this generalization of the description of gauge theories is applied to the case of YangMills theories with gauge group SU(N) to consider especially the application to the electroweak theory as it appears in the Standard Model. The modifications of the lepton-, Higgs- and gauge field sector of the extended Lagrangian of the electroweak theory maintaining local gauge invariance under SU(2)L ⊗ U(1)Y transformations are investigated. There appear additional interaction terms between the leptons or the Higgs particle respectively with the photon and the W- and Z-bosons as well as additional self-interaction terms of these gauge bosons themselves. It is remarkable that in the quark sector where the full gauge group of the Standard Model, SU(3)c ⊗ SU(2)L ⊗ U(1)Y, has to be considered there arise coupling terms between the gluons und the W- and Z-bosons which means that the electroweak theory is not separated from quantum chromodynamics anymore. © 2011 World Scientific Publishing Company. Source


Iwata Y.,Helmholtz Center for Heavy Ion Research | Maruhn J.A.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2011

The tensor and spin-orbit forces contribute essentially to the formation of the spin mean field, and give rise to the same dynamical effect, namely spin polarization. In this paper, based on time-dependent density functional calculations, we show that the tensor force, which usually acts like a small correction to the spin-orbit force, becomes more important in heavy-ion reactions and the effect increases with the mass of the system. © 2011 American Physical Society. Source


Senft C.,Goethe University Frankfurt
Acta neurochirurgica. Supplement | Year: 2011

Aiming at providing high-class evidence regarding the use of intraoperative MRI (ioMRI), we are conducting a prospective randomized controlled trial. Adult patients with contrast enhancing lesions suspicious of malignant gliomas scheduled to undergo radiologically complete tumor resection are eligible to enter this trial. After giving their informed consent, patients are randomized to undergo either ioMRI-guided or conventional microneurosurgical tumor resection. To assess the extent of resection, pre- and early postoperative high-field MR images are obtained to perform volumetric analyses. Primary endpoint of the study is the rate of radiologically complete tumor resections. After the inclusion of 35 patients, we performed an interim analysis. In six patients, histopathological examination revealed metastases, so they were excluded from further analyses. Thus, data from 29 patients with gliomas could be analyzed. There were no significant differences in patient age (P=0.28) or preoperative tumor sizes (P=0.40) between the two treatment groups. We observed a trend towards a higher rate of complete tumor resections in the ioMRI-group compared to the control group (P=0.07). Postoperative tumor volumes were significantly lower in the ioMRI-group than in the control group (P<0.05). The use of ioMRI appears to be associated with a higher rate of radiographically complete as well as near total tumor resections compared to conventional microneurosurgery. Source


Doerr H.W.,Goethe University Frankfurt
Expert Review of Vaccines | Year: 2013

In the Second Conference on Controversies in Vaccination in Adults, leading vaccine experts among manufacturers, physicians, microbiologists, virologists, immunologists and public health specialists came together to discuss recent approaches, developments and strategies in vaccination against worldwide pressing epidemic and endemic infectious diseases (pneumococcal, staphylococcal, influenza, papillomavirus-associated tumors, varicella-zoster, AIDS and tuberculosis), and noninfectious epidemics (atherosclerosis and smoking) outlining arguments surrounding the progress of vaccines. © 2013 Expert Reviews Ltd. Source


Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces ‘big data’ exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics.The Pharmacogenomics Journal advance online publication, 3 May 2016; doi:10.1038/tpj.2016.28. © 2016 Macmillan Publishers Limited Source


Rosewich M.,Goethe University Frankfurt
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology | Year: 2010

Ultra-short course immunotherapy (uSCIT) has shown good efficacy and tolerability in children and adolescents with seasonal allergic rhinitis (SAR), conjunctivitis and/or asthma in clinical studies. Here, we investigate the efficacy of uSCIT in the juvenile subpopulation of a 3-year post-marketing surveillance (PMS) study. To assess the differences in the efficacy of uSCIT between adults and children respectively adolescents enrolled in a PMS study. In a prospective open study 422 patients aged 6-18 years with SAR, conjunctivitis and/or asthma received four pre-seasonal injections with pollen allergoids formulated with monophosphoryl lipid A (MPL, Pollinex Quattro) over a minimum of 3 weeks. Efficacy was evaluated by response to therapy and consumption of anti-allergic medication during the pollen season. Tolerability was evaluated by patients' acceptance of therapy. These results were compared with the adult subpopulation of this study. Response to treatment was assessed as good or very good in 94% of patients, mirroring findings for the entire cohort. Further improvements were noted in patients receiving subsequent courses of therapy. Anti-allergic medication use decreased from 83% to 24% of patients after the first treatment course (p < 0.0001). Therapy was well accepted by children/adolescents and considered 'very good' or 'good' by 93% of juveniles. No serious adverse events or cases of anaphylaxis were reported. This subanalysis indicated that uSCIT with Pollinex Quattro had similar efficacy and tolerability in children/adolescents and adults. The convenient dosing regimen and favourable safety profile of uSCIT may support a wider uptake of uSCIT in this patient population. © 2009 John Wiley & Sons A/S. Source


Giacosa F.,Goethe University Frankfurt | Pagliara G.,University of Ferrara
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

We present the calculation of the spectral function of an unstable scalar boson coupled to fermions as resulting from the resummation of the one-loop diagrams in the scalar particle self-energy. We work with a large but finite high-energy cutoff; in this way, the spectral function of the scalar field is always correctly normalized to unity, independent of the value of the cutoff. We show that this high-energy cutoff affects the Breit-Wigner width of the unstable particle: the larger the cutoff, the smaller is the width at fixed coupling. Thus, the existence of a high-energy cutoff (alias minimal length), and for instance the possible opening of new degrees of freedom beyond that energy scale, could then be in principle proven by measuring, at lower energy scales, the line shape of the unstable scalar state. Although the Lagrangian here considered represents only a toy model, we discuss possible future extensions of our work which could be relevant for particle physics phenomenology. © 2013 American Physical Society. Source


Bicudo P.,University of Lisbon | Wagner M.,Goethe University Frankfurt
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

Utilizing lattice QCD results for the potential of two static antiquarks and two dynamical quarks as well as quark model techniques for the dynamics of two heavy antiquarks in a cloud of two light quarks, we are provided with an accurate framework for the study of possibly existing heavy-heavy-light-light tetraquarks. Among the possible quantum numbers of such a system, we find binding in only one channel the scalar isosinglet. Solving the Schrödinger equation for the displacement of the heavy antiquarks and taking systematic errors into account, we find an antibottom-antibottom-light-light bound state with a confidence level of around 1.8σ-3.0σ and binding energy of approximately 30-57 MeV. © 2013 American Physical Society. Source


Geiger H.,Goethe University Frankfurt | Wanner C.,Universitatsklinik Wurzburg
CKJ: Clinical Kidney Journal | Year: 2012

Although the following text will focus on magnesium in disease, its role in healthy subjects during physical exercise when used as a supplement to enhance performance is also noteworthy. Low serum magnesium levels are associated with metabolic syndrome, Type 2 diabetes mellitus (T2DM) and hypertension; consequently, some individuals benefit from magnesium supplementation: increasing magnesium consumption appears to prevent high blood pressure, and higher serum magnesium levels are associated with a lower risk of developing a metabolic syndrome. There are, however, conflicting study results regarding magnesium administration with myocardial infarction with and without reperfusion therapy. There was a long controversy as to whether or not magnesium should be given as a first-line medication. As the most recent trials have not shown any difference in outcome, intravenous magnesium cannot be recommended in patients with myocardial infarction today. However, magnesium has its indication in patients with torsade de pointes and has been given successfully to patients with digoxin-induced arrhythmia or life-threatening ventricular arrhythmias. Magnesium sulphate as an intravenous infusion also has an important established therapeutic role in pregnant women with pre-eclampsia as it decreases the risk of eclamptic seizures by half compared with placebo. © The Author 2012. Source


Stangier U.,Goethe University Frankfurt
Current Psychiatry Reports | Year: 2016

Social anxiety disorder (SAD) is a highly prevalent and chronic disorder that causes considerable psychosocial impairment. This article reviews recent changes in the definition of SAD in DSM-5 and summarizes the current evidence for effective cognitive-behavioral treatments in adults, children, and adolescents. Current data suggests that cognitive-behavioral therapy (CBT) is efficacious in the treatment of this condition. Among different CBT approaches, individual cognitive therapy may be associated with the largest effect sizes. In this review, interventions targeting dysfunctional cognitive processes that contribute to the effective treatment of SAD are discussed. Some recent findings from neuroimaging research and studies on the augmentation of CBT using neuroenhancers indicate that changes in emotion regulation as well as fear extinction are important psychological mediators of positive outcome. Furthermore, internet-delivered CBT is a promising field of technological innovation that may improve access to effective treatments. Despite the availability of effective treatments, treatment-resistant SAD remains a common problem in clinical practice that requires more research efforts. Finally, potential areas for further development of CBT as well as its dissemination in health care are summarized. © 2016, Springer Science+Business Media New York. Source


Fulda S.,Goethe University Frankfurt
Mitochondrion | Year: 2014

Small-molecule inhibitors that antagonize anti-apoptotic Bcl-2 proteins such as BH3 mimetics are currently considered as promising cancer therapeutics to engage the mitochondrial pathway of apoptosis in cancer cells. However, BH3 mimetics may be effective as monotherapy only in cancers that critically depend on anti-apoptotic Bcl-2 proteins for their survival. Since most cancers have evolved multiple strategies to evade programmed cell death, concomitant targeting of several signaling transduction pathways becomes more and more relevant. The current review highlights the potential of combined inhibition of anti-apoptotic Bcl-2 proteins together with the PI3K/Akt/mTOR signaling cascade to trigger apoptosis in cancer cells. © 2014 Elsevier B.V. and Mitochondria Research Society. Source


Siebenhofer A.,Goethe University Frankfurt
The Cochrane database of systematic reviews | Year: 2013

All major guidelines for antihypertensive therapy recommend weight loss; anti-obesity drugs might be a helpful option. Primary objectives:To assess the long-term effects of pharmacologically induced reduction in body weight with orlistat, sibutramine or rimonabant on:- all cause mortality - cardiovascular morbidity - adverse events Secondary objectives: - changes in systolic and/or diastolic blood pressure - body weight reduction even though sibutramine and rimonabant have been withdrawn from the market. Studies were obtained from computerised searches of Ovid MEDLINE, EMBASE, CENTRAL and from hand searches in reference lists and systematic reviews (status as of 17(th) August, 2012). Randomized controlled trials in adult hypertensive patients with a study duration of at least 24 weeks comparing pharmacologic interventions (orlistat, sibutramine, rimonabant) for weight loss with placebo. Two authors independently assessed risk of bias and extracted data. Studies were pooled using fixed-effect meta-analysis in the absence of significant heterogeneity between studies (p>0.1). Otherwise, we used the random effects method and investigated the cause of heterogeneity. After the updated literature search, the number of studies remained the same, with eight studies comparing orlistat or sibutramine to placebo fulfilling our inclusion criteria. No relevant studies investigating rimonabant for weight loss were identified. No study included mortality and cardiovascular morbidity as a pre-defined outcome. Incidence of gastrointestinal side effects was consistently higher in orlistat treated vs. placebo treated patients. Most frequent side effects with sibutramine were dry mouth, constipation and headache. Patients assigned to weight loss diets, orlistat or sibutramine reduced their body weight more effectively than patients in the usual care/placebo groups. Blood pressure reduction in patients treated with orlistat was for systolic blood pressure (SBP): weighted mean difference (WMD): -2.5 mm Hg; 95% CI, -4.0 to -0.9 mm Hg and for diastolic blood pressure (DBP): WMD -1.9 mm Hg; 95% CI, -3.0 to -0.9 mm Hg. Meta-analysis showed DBP increase under therapy with sibutramine: WMD +3.2 mm Hg; 95%CI +1.4 to +4.9 mm Hg. In patients with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree. In the same trials, orlistat reduced blood pressure and sibutramine increased blood pressure. No trials investigating rimonabant in people with elevated blood pressure could be included. Long-term trials assessing the effect of orlistat, sibutramine and rimonabant on mortality and morbidity are lacking. Rimonabant and sibutramine have been withdrawn from the market for the time being. Source


Watkins N.J.,Northumbria University | Bohnsack M.T.,Goethe University Frankfurt
Wiley Interdisciplinary Reviews: RNA | Year: 2012

Box C/D and H/ACA RNPs are essential ribonucleoprotein particles that are found throughout both eukaryotes [small nucleolar RNPs (snoRNPs)] and archaea [snoRNP-like complexes (sRNPs)]. These complexes catalyze the site-specific pseudouridylation and most of the methylation of ribosomal RNA (rRNA). The numerous modifications, which are clustered in functionally important regions of the rRNA, are important for rRNA folding and ribosome function. The RNA component of the complexes [small nucleolar RNA (snoRNA) or small RNA (sRNA)] functions in substrate binding by base pairing with the target site and as a scaffold coordinating the organization of the complex. In eukaryotes, a subset of snoRNPs do not catalyze modification but, through base pairing to the rRNA or flanking precursor sequences, direct pre-rRNA folding and are essential for rRNA processing. In the last few years there have been significant advances in our understanding of the structure of archaeal sRNPs. High resolution structures of the archaeal C/D and H/ACA sRNPs have not only provided a detailed understanding of the molecular architecture of these complexes but also produced key insights into substrate binding and product release. In both cases, this is mediated by significant movement in the complexes. Advances have also been made in our knowledge of snoRNP recruitment and release from pre-ribosome complexes in eukaryotes. New snoRNA-rRNA interactions have been documented, and the roles of RNA helicases in releasing snoRNP complexes from the rRNA have been described. © 2011 John Wiley & Sons, Ltd. Source


Groll A.H.,University of Munster | Castagnola E.,Infectious Diseases Unit | Cesaro S.,Pediatric Hematology Oncology | Dalle J.-H.,University Paris Diderot | And 6 more authors.
The Lancet Oncology | Year: 2014

Invasive opportunistic fungal diseases (IFDs) are important causes of morbidity and mortality in paediatric patients with cancer and those who have had an allogeneic haemopoietic stem-cell transplantation (HSCT). Apart from differences in underlying disorders and comorbidities relative to those of adults, IFDs in infants, children, and adolescents are unique with respect to their epidemiology, the usefulness of diagnostic methods, the pharmacology and dosing of antifungal agents, and the absence of interventional phase 3 clinical trials for guidance of evidence-based decisions. To better define the state of knowledge on IFDs in paediatric patients with cancer and allogeneic HSCT and to improve IFD diagnosis, prevention, and management, the Fourth European Conference on Infections in Leukaemia (ECIL-4) in 2011 convened a group that reviewed the scientific literature on IFDs and graded the available quality of evidence according to the Infectious Diseases Society of America grading system. The final considerations and recommendations of the group are summarised in this manuscript. © 2014 Elsevier Ltd. Source


Schulte-Oehlmann U.,Goethe University Frankfurt
Reviews of Environmental Contamination and Toxicology | Year: 2011

As a result of the European Parliament approving a new EU pesticide regulation (1107/2009/EC replacing directive 91/414/EEC) and a directive on the sustainable use of pesticides (2009/128/EC), in October 2009, various active ingredients are likely to be banned for use as pesticides. The use of pesticides that are carcinogenic, mutagenic, and toxic to reproduction, or that have endocrine-disrupting properties, shall no longer be authorized for use. Active ingredients that are persistent, bioaccumulative and toxic (PBT), or very persistent and very bioaccumulative (vPvB) shall be phased out as well. The decision-making process for setting test criteria for endocrine-disrupting pesticides is pending and is planned to be finalized by 2013 (EU, 2009a). The new regulation becomes effective in June 2011. According to directive 2009/128/EC, all member states are required to adopt National Action Plans for reducing the human health and environmental risks of pesticide use. The protection of the aquatic environment and drinking water supplies from pesticides, and the obligation to undertake corresponding control measures, was particularly highlighted. © 2011 Springer Science+Business Media, LLC. Source


Bereiter-Hahn J.,Goethe University Frankfurt
Protoplasma | Year: 2014

The process of aging remains a great riddle. Production of reactive oxygen species (ROS) by mitochondria is an inevitable by-product of respiration, which has led to a hypothesis proposing the oxidative impairment of mitochondrial components (e.g., mtDNA, proteins, lipids) that initiates a vicious cycle of dysfunctional respiratory complexes producing more ROS, which again impairs function. This does not exclude other processes acting in parallel or targets for ROS action in other organelles than mitochondria. Given that aging is defined as the process leading to death, the role of mitochondria-based impairments in those organ systems responsible for human death (e.g., the cardiovascular system, cerebral dysfunction, and cancer) is described within the context of "garbage" accumulation and increasing insulin resistance, type 2 diabetes, and glycation of proteins. Mitochondrial mass, fusion, and fission are important factors in coping with impaired function. Both biogenesis of mitochondria and their degradation are important regulatory mechanisms stimulated by physical exercise and contribute to healthy aging. The hypothesis of mitochondria-related aging should be revised to account for the limitations of the degradative capacity of the lysosomal system. The processes involved in mitochondria-based impairments are very similar across a large range of organisms. Therefore, studies on model organisms from yeast, fungi, nematodes, flies to vertebrates, and from cells to organisms also add considerably to the understanding of human aging. © 2013 Springer-Verlag Wien. Source


Fulda S.,Goethe University Frankfurt
Seminars in Cancer Biology | Year: 2015

Programmed cell death via apoptosis is characteristically disturbed in human cancers. This facilitates not only tumor formation and progression, but also treatment resistance. Since many currently applied anticancer treatment strategies rely on intact cell death signaling pathways for their therapeutic efficacy, a better understanding of the regulatory mechanisms that control cell death signaling pathways is critical to bypass resistance. Thus, reactivation of cell death programs in cancer cells may open new perspectives for more effective and more tumor-selective, yet less toxic anticancer therapies. © 2014 Elsevier Ltd. Source


Radmark O.,Karolinska Institutet | Werz O.,Friedrich - Schiller University of Jena | Steinhilber D.,Goethe University Frankfurt | Samuelsson B.,Karolinska Institutet
Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids | Year: 2015

5-Lipoxygenase (5-LOX) catalyzes two steps in the biosynthesis of leukotrienes (LTs), lipid mediators of inflammation derived from arachidonic acid. In this review we focus on 5-LOX biochemistry including 5-LOX interacting proteins and regulation of enzyme activity. LTs function in normal host defense, and have roles in many disease states where acute or chronic inflammation is part of the pathophysiology, as briefly summarized at the end of this chapter. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance. © 2014 Elsevier B.V.All rights reserved. Source


Iozzo R.V.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt
Matrix Biology | Year: 2015

We provide a comprehensive classification of the proteoglycan gene families and respective protein cores. This updated nomenclature is based on three criteria: Cellular and subcellular location, overall gene/protein homology, and the utilization of specific protein modules within their respective protein cores. These three signatures were utilized to design four major classes of proteoglycans with distinct forms and functions: the intracellular, cell-surface, pericellular and extracellular proteoglycans. The proposed nomenclature encompasses forty-three distinct proteoglycan-encoding genes and many alternatively-spliced variants. The biological functions of these four proteoglycan families are critically assessed in development, cancer and angiogenesis, and in various acquired and genetic diseases where their expression is aberrant. © 2015. Source


Fulda S.,Goethe University Frankfurt
Advances in Experimental Medicine and Biology | Year: 2014

The concept to exploit death receptors for cancer therapy is very attractive, since these cell surface receptors have a direct connection to the intracellular cell death machinery. Among the death receptor superfamily, the tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) receptor/ligand system is of special interest. TRAIL receptor agonists have recently entered the stage of clinical evaluation for the treatment of human cancers. Further insights into the regulatory mechanisms of TRAIL signaling will help to better understand the determinants of TRAIL sensitivity versus resistance of human cancers. © 2014 Springer-Verlag London. Source


Inhibitor of apoptosis (IAP) proteins play a critical role in the control of survival and cell death by regulating key signaling events such as caspase activation and NF-&kgreenB signaling. Because aberrantly high expression of IAP proteins represents a frequent oncogenic event in human cancers, therapeutic targeting of IAP proteins is considered as a promising approach. Several small-molecule pharmacologic inhibitors of IAP proteins that mimic the binding domain of the endogenous IAP antagonist second mitochondrial activator of caspases (Smac) to IAP proteins have been developed over the past few years. IAP antagonists have been shown in various preclinical cancer models to either directly initiate cell death or, alternatively, to prime cancer cells for cytotoxic therapies by lowering the threshold for cell death induction. IAP antagonists (i.e., GDC-0917/CUDC-427, LCL161, AT-406, HGS1029, and TL32711) are currently under evaluation in early clinical trials alone or in combination regimens. Thus, the concept to therapeutically target IAP proteins in human cancer has in principle been successfully transferred into a clinical setting and warrants further evaluation as a treatment approach. Clin Cancer Res; 20(2); 289-95. © 2013 AACR. Source


Zagrebaev V.I.,Joint Institute for Nuclear Research | Greiner W.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2013

Problems of production and study of new neutron-enriched heavy nuclei are discussed. Low-energy multinucleon transfer reactions are shown to be quite appropriate for this purpose. Reactions with actinide beams and targets are of special interest for synthesis of new neutron-enriched transfermium nuclei and not-yet-known nuclei with closed neutron shell N=126 having the largest impact on the astrophysical r-process. The estimated cross sections for the production of these nuclei look very promising for planning such experiments at currently available accelerators. These experiments, however, are rather expensive and difficult to perform because of low intensities of the massive projectile beams and problems of separating and detecting the heavy reaction products. Thus, realistic predictions of the corresponding cross sections for different projectile-target combinations are definitely required. Some uncertainty still remains in the values of several parameters used for describing the low-energy nuclear dynamics. This uncertainty does not allow one to perform very accurate predictions for the productions of new heavier-than-target (trans-target) nuclei in multinucleon transfer reactions. Most of these parameters (nucleon transfer rate, nuclear viscosity, and fission barriers) are fundamental characteristics of low-energy nuclear dynamics. Determination of the values of these parameters (as well as their temperature dependence) is of significance in its own right. The available experimental data on the production of heavy nuclei in low-energy multinucleon transfer reactions are still insufficient and fragmentary. Several new experiments are proposed, these include those in which the role of shell effects in reaction dynamics can be better clarified. © 2013 American Physical Society. Source


Dimmeler S.,Goethe University Frankfurt
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2010

Cell therapy is a promising option for treating ischemic diseases and heart failure. Bone marrow-derived vasculogenic cells, including progenitor cells and proangiogenic cells, have been shown to augment the functional recovery after ischemia. However, cardiovascular diseases affect the functional activity of the endogenous progenitor cell pools. The local microenvironment, also termed the stem cell niche, provides essential cues that maintain stem and progenitor cell functions and direct cell fate decisions in the bone marrow. A disturbed niche might lead to cell dysfunction (eg, by exhaustion). In addition, the niche controls mobilization of the cells into the circulation. This review will discuss the impact of cardiovascular disease on stem cell niches and summarize strategies targeting the niche for mobilization of vasculogenic cells. © 2010 American Heart Association, Inc. Source


Medvedev N.,German Electron Synchrotron | Jeschke H.O.,Goethe University Frankfurt | Ziaja B.,German Electron Synchrotron | Ziaja B.,Polish Academy of Sciences
New Journal of Physics | Year: 2013

In this paper, we present a novel theoretical approach, which allows the study of nonequilibrium dynamics of both electrons and atoms/ions within free-electron laser excited semiconductors at femtosecond time scales. The approach consists of the Monte-Carlo method treating photoabsorption, high-energy-electron and core-hole kinetics and relaxation processes. Low-energy electrons localized within the valence and conduction bands of the target are treated with a temperature equation, including source terms, defined by the exchange of energy and particles with high-energy electrons and atoms. We follow the atomic motion with the molecular dynamics method on the changing potential energy surface. The changes of the potential energy surface and of the electron band structure are calculated at each time step with the help of the tight-binding method. Such a combination of methods enables investigation of nonequilibrium structural changes within materials under extreme ultraviolet (XUV) femtosecond irradiation. Our analysis performed for diamond irradiated with an XUV femtosecond laser pulse predicts for the first time in this wavelength regime the nonthermal phase transition from diamond to graphite. Similar to the case of visible light irradiation, this transition takes place within a few tens of femtoseconds and is caused by changes of the interatomic potential induced by ultrafast electronic excitations. It thus occurs well before the heating stimulated by electron-phonon coupling starts to play a role. This allows us to conclude that this transition is nonthermal and represents a general mechanism of the response of solids to ultrafast electron excitations. © IOP Publishing and Deutsche Physikalische Gesellschaft. Source


Linkersdorfer J.,Goethe University Frankfurt
Kindheit und Entwicklung | Year: 2011

Cognitive and neural correlates of developmental dyslexia are reviewed. Beginning with a description of different cognitive and neurobiological theories of developmental dyslexia, findings from post-mortem analyses and from functional and structural imaging studies are discussed. The results indicate that developmental dyslexia is a multidimensional phenomenon involving different cognitive, sensory, and motor problems and appears to be associated with specific disruptions of brain systems. Accordingly, individual profiles of the disorder on the cognitive and neural level should receive more attention in future research. © Hogrefe Verlag, Göttingen 2011. Source


Fokas E.,University of Oxford | Fokas E.,Goethe University Frankfurt | McKenna W.G.,University of Oxford | Muschel R.J.,University of Oxford
Cancer and Metastasis Reviews | Year: 2012

Tumor cells exploit their microenvironment by growth factors and cytokines such as vascular endothelial growth factor (VEGF) to stimulate abnormal vessel formation that is leaky and tortuous, causing irregular blood flow. The combination of poor perfusion, raised interstitial fluid pressure and areas of vascular collapse leads to hypoxia within tumor. The latter activates factors such as hypoxia inducible factor 1 (HIF-1) that serve to make cancer cells more aggressive and also markedly influences the response of malignant tumors to conventional irradiation and chemotherapy. Accumulating data now suggest that blockade of oncogenic signaling, for example by PI3K/Akt/mTOR inhibitors, might consist a promising strategy since these agents do not only possess antitumor effects but can also alter tumor vasculature and oxygenation to improve the response to radiation and chemotherapy. In many cases, these changes are related to downregulation of HIF-1α and VEGF. Here, we review the pathophysiology of tumor microenvironment (TME) and how it adversely affects cancer treatment. The complex interaction of tumor vasculature and radiotherapy is examined together the preclinical evidence supporting a proinvasive/metastatic role for ionising radiation. We will discuss the expanding role of oncogenic signaling, especially PI3K/Akt/mTOR, on tumor angiogenesis. Special emphasis will be paid to the potential of different oncogenic pathways blockade and other indirect antivascular strategies to alter the TME for the benefit of cancer treatment, as an alternative to the classical angiogenetic treatment. © 2012 Springer Science+Business Media, LLC. Source


Shallow fore-reef areas worldwide are usually characterized by spurs and grooves. A comparison of examples from the three world oceans suggests that Indo-Pacific spurs and grooves are shaped predominantly by erosion, whereas western Atlantic spur and groove systems are largely a product of constructive processes. I propose that this difference is caused by regional differences in Holocene sea-level change, which controlled exposure to waves and currents, and reef-accretion rates. The transgressive-regressive sea-level curve in the Indo-Pacific realm, i.e., the Mid-to-Late Holocene sea-level fall in these areas has maintained high-energy conditions in the shallow fore reef. Higher exposure to waves and currents favors erosion and leads to a dominance of crustose coralline algae that have relatively slow growth rates. In the western Atlantic, the transgressive Holocene sea level has caused Mid-to-Late Holocene deepening and has maintained accommodation space for reef accretion. Fast-growing acroporid corals thrive under lower exposure and are more common than coralline algae. The fossil record of the spur and groove system is rather poor, which is probably a consequence of the need of excellent, three-dimensional outcrops for identification. © Springer-Verlag 2010. Source


Cuntz H.,Goethe University Frankfurt | Cuntz H.,Ernst Strungmann Institute in Cooperation with Max Planck Society
Frontiers in Neuroanatomy | Year: 2012

Much is known about the computation in individual neurons in the cortical column. Also, the selective connectivity between many cortical neuron types has been studied in great detail. However, due to the complexity of this microcircuitry its functional role within the cortical column remains a mystery. Some of the wiring behavior between neurons can be interpreted directly from their particular dendritic and axonal shapes. Here, I describe the dendritic density field (DDF) as one key element that remains to be better understood. I sketch an approach to relate DDFs in general to their underlying potential connectivity schemes. As an example, I show how the characteristic shape of a cortical pyramidal cell appears as a direct consequence of connecting inputs arranged in two separate parallel layers. © 2012 Cuntz. Source


Kober M.,Goethe University Frankfurt
Classical and Quantum Gravity | Year: 2011

General relativity under the assumption of noncommuting components of the tetrad field is considered in this paper. Since the algebraic properties of the tetrad field representing the gravitational field are assumed to correspond to the noncommutativity algebra of the coordinates in the canonical case of noncommutative geometry, this idea is closely related to noncommutative geometry as well as to canonical quantization of gravity. According to this presupposition, generalized field equations for general relativity are derived which are obtained by replacing the usual tetrad field by the tetrad field operator within the actions and then building expectation values of the corresponding field equations between coherent states. These coherent states refer to creation and annihilation operators created from the components of the tetrad field operator. In this sense, the obtained theory could be regarded as a kind of semiclassical approximation of a complete quantum description of gravity. The consideration presupposes a special choice of the tensor determining the algebra providing a division of spacetime into two two-dimensional planes. © 2011 IOP Publishing Ltd. Source


Daum B.,Max Planck Institute of Biophysics | Walter A.,Max Planck Institute of Biophysics | Horst A.,Max Planck Institute of Biophysics | Osiewacz H.D.,Goethe University Frankfurt | Kuhlbrandt W.,Max Planck Institute of Biophysics
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

Aging is one of the most fundamental, yet least understood biological processes that affect all forms of eukaryotic life. Mitochondria are intimately involved in aging, but the underlying molecular mechanisms are largely unknown. Electron cryotomography of whole mitochondria from the aging model organism Podospora anserina revealed profound age-dependent changes in membrane architecture. With increasing age, the typical cristae disappear and the inner membrane vesiculates. The ATP synthase dimers that form rows at the cristae tips dissociate into monomers in inner-membrane vesicles, and the membrane curvature at the ATP synthase inverts. Dissociation of the ATP synthase dimer may involve the peptidyl prolyl isomerase cyclophilin D. Finally, the outer membrane ruptures near large contact-site complexes, releasing apoptogens into the cytoplasm. Inner-membrane vesiculation and dissociation of ATP synthase dimers would impair the ability of mitochondria to supply the cell with sufficient ATP to maintain essential cellular functions. Source


Ionov D.A.,Jean Monnet University | Ionov D.A.,CNRS Magmas and Volcanoes Laboratory | Ionov D.A.,Goethe University Frankfurt
Journal of Petrology | Year: 2010

Peridotite xenoliths in arc volcanoes are very rare, usually small and remain poorly studied. Much of the earlier work focused on peridotites affected by re-crystallization, metasomatism and veining that took place shortly before the eruption of the host magmas; such lithologies may not be widespread in the mantle wedge. This study reports petrographic, major and trace element data for 17 large, fresh peridotite xenoliths from the active Avacha volcano and discusses the origin of supra-subduction zone lithospheric mantle, in particular the role and characteristics of partial melting and metasomatism. The xenoliths are spinel harzburgites containing interstitial cpx (1·5-3%) and amphibole (≤1%). Nearly all are medium- to coarse-grained with protogranular to granoblastic microstructures; some have fine-grained domains and thin cross-cutting veins of secondary opx and olivine. Core-rim zoning and unmixing of cpx and spinel in coarse opx indicate long-term cooling to ≤900-1000°C; Cr#Sp and Al and Cr in opx are correlated with equilibration temperatures. The peridotites are highly refractory, with ≥44% MgO and very low Al2O3 and CaO (0·4-0·9%), TiO2 (≤0.01%), Na2O (≤0.03%), K2O and P2O5 (below detection) and REE in whole-rocks, ≤2·1% Al2O3 in opx and ≤0·1-0·3% Na2O in cpx. Comparisons of Mg, Al and Fe contents with melting experiments indicate 28-35% melt extraction at ≤1 to 2 GPa, in line with the absence of primary cpx and high Mg#Ol (0·907-0·918) and Cr#Sp (0·53-0·65). Bulk-rock Al2O3 is a more robust melt extraction index than Cr#Sp, Mg#Ol and Mg#WR. Forearc harzburgites and certain xenoliths from the Western Pacific share many of these characteristics with the Avacha suite and may have similar origins. A distinctive feature of the Avacha harzburgites is a combination of variable but commonly high modal opx (18-30%) with very low modal cpx. At a given olivine or MgO content, they have higher opx and SiO2, and lower cpx (as well as Al2O3 and CaO) than typical refractory peridotite xenoliths in continental basalts. These features may indicate fluid fluxing during melting in the mantle wedge. Alternatively, they could have been produced after partial melting by selective metasomatic enrichment in SiO2 by fluids to transform some olivine into opx, although the latter mechanism is hard to reconcile with the very low alkalis and REE contents and the absence of silica correlation with fluid-mobile elements. Bulk-rock enrichments in silica and opx are unrelated to the presence or abundance of late-stage, fine-grained materials and are due to an ancient event rather than recent re-crystallization and veining. © The Author 2010. Published by Oxford University Press. Source


Linnyk O.,Goethe University Frankfurt
Journal of Physics G: Nuclear and Particle Physics | Year: 2011

We address the dilepton production by the constituents of the strongly interacting quark-gluon plasma (sQGP). In order to make quantitative predictions for dilepton rates at experimentally relevant low dilepton mass (O(1 GeV)) and strong coupling (αS ∼ 0.5-1), we take into account nonperturbative spectral functions and self-energies of the quarks, antiquarks and gluons. For this purpose, we use parametrizations of the quark and gluon propagators provided by the dynamical quasi-particle model (DQPM) matched to reproduce lattice quantum chromodynamics (QCD) data. The DQPM describes QCD properties in terms of the single-particle Green's functions and leads to the notion of the constituents of the sQGP being effective quasiparticles, which are massive and have broad spectral functions (due to large interaction rates). By 'dressing' the quark and gluon lines with the effective propagators, we derive the off-shell cross sections for dilepton production in the reactions q +q̄ → l+l- (Born mechanism), q +q̄ → g + l+l- (quark annihilationwith the gluon bremsstrahlung in the final state), q(q̄)+g → q(q̄)+ l+l- (gluon-Compton scattering), g → q +q̄ +l+l - and q(q̄) → q(q̄)+g+l+l - (virtual gluon decay, virtual quark decay). In contrast to previous calculations of these cross sections, we account for virtualities of all the quarks and gluons. We find that finite masses of the effective quasi-particles not only screen the singularities typical of the perturbative cross sections with massless quarks, but also modify the shape of the dilepton production cross sections, especially at low dilepton mass Q and at the edges of the phase space. Finally, we use the calculated mass-dependent cross sections to identify the dependence of the dilepton rates on the spectral function widths of the initial and final quarks and gluons, which has not been estimated so far. The results demonstrate that the multiple partonic scatterings encoded in the broad spectral functions of the dynamical quasi-particles have considerable effect on the dilepton rates. (Some figures in this article are in colour only in the electronic version). © 2011 IOP Publishing Ltd. Source


Modesto L.,Perimeter Institute for Theoretical Physics | Moffat J.W.,Perimeter Institute for Theoretical Physics | Moffat J.W.,University of Waterloo | Nicolini P.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In this Letter we derive the gravity field equations by varying the action for an ultraviolet complete quantum gravity. Then we consider the case of a static source term and we determine an exact black hole solution. As a result we find a regular spacetime geometry: in place of the conventional curvature singularity extreme energy fluctuations of the gravitational field at small length scales provide an effective cosmological constant in a region locally described in terms of a de Sitter space. We show that the new metric coincides with the noncommutative geometry inspired Schwarzschild black hole. Indeed, we show that the ultraviolet complete quantum gravity, generated by ordinary matter is the dual theory of ordinary Einstein gravity coupled to a noncommutative smeared matter. In other words we obtain further insights about that quantum gravity mechanism which improves Einstein gravity in the vicinity of curvature singularities. This corroborates all the existing literature in the physics and phenomenology of noncommutative black holes. © 2010 Elsevier B.V. Source


Rau J.,Goethe University Frankfurt
Foundations of Physics | Year: 2011

I show that quantum theory is the only probabilistic framework that permits arbitrary processes to be emulated by sequences of local measurements. This supports the view that, contrary to conventional wisdom, measurement should not be regarded as a complex phenomenon in need of a dynamical explanation but rather as a primitive-and perhaps the only primitive-operation of the theory. © 2010 Springer Science+Business Media, LLC. Source


Priesemann V.,Max Planck Institute for Brain Research | Valderrama M.,University of Los Andes, Colombia | Wibral M.,Goethe University Frankfurt | Le Van Quyen M.,French Institute of Health and Medical Research
PLoS Computational Biology | Year: 2013

Neuronal activity differs between wakefulness and sleep states. In contrast, an attractor state, called self-organized critical (SOC), was proposed to govern brain dynamics because it allows for optimal information coding. But is the human brain SOC for each vigilance state despite the variations in neuronal dynamics? We characterized neuronal avalanches - spatiotemporal waves of enhanced activity - from dense intracranial depth recordings in humans. We showed that avalanche distributions closely follow a power law - the hallmark feature of SOC - for each vigilance state. However, avalanches clearly differ with vigilance states: slow wave sleep (SWS) shows large avalanches, wakefulness intermediate, and rapid eye movement (REM) sleep small ones. Our SOC model, together with the data, suggested first that the differences are mediated by global but tiny changes in synaptic strength, and second, that the changes with vigilance states reflect small deviations from criticality to the subcritical regime, implying that the human brain does not operate at criticality proper but close to SOC. Independent of criticality, the analysis confirms that SWS shows increased correlations between cortical areas, and reveals that REM sleep shows more fragmented cortical dynamics. © 2013 Priesemann et al. Source


Kulic I.M.,Charles Sadron Institute | Kulic M.L.,Goethe University Frankfurt
Physical Review Letters | Year: 2013

From microscopic fluid clusters to macroscopic droplets, the structure of fluids is governed by the van der Waals force, a force that acts between polarizable objects. In this Letter, we derive a general theory that describes the nonequilibrium counterpart to the van der Waals force, which emerges in spatially coherently fluctuating electromagnetic fields. We describe the formation of a novel and complex hierarchy of self-organized morphologies in magnetic and dielectric colloid systems. Most striking among these morphologies are dipolar foams - colloidal superstructures that swell against gravity and display a high sensitivity to the applied field. We discuss the dominance of many-body forces and derive the equation of state for a material formed by the coherent van der Waals force. Our theory is applied to recent experiments in paramagnetic colloidal systems and a new experiment is suggested to test the theory. © 2013 American Physical Society. Source


Betsch C.,University of Erfurt | Wicker S.,Goethe University Frankfurt
Vaccine | Year: 2014

Introduction: Healthcare personnel (HCP) are often under-vaccinated. The aim of this study was to evaluate occupational physicians' potential role by assessing relations between their knowledge and attitudes regarding HCP vaccination and the extent to which official vaccination recommendations are communicated. Methods: Cross-sectional survey, n= 135 occupational physicians. Results: Occupational physicians who treat HCP recommend vaccinations more often to HCP when they have better knowledge of official vaccination recommendations and a more positive attitude towards vaccination compared to physicians with less such knowledge or a more negative attitude. The attitude towards vaccination most strongly affects whether occupational physicians recommend the measles, mumps, and rubella (MMR) vaccination: physicians with less positive attitudes recommend MMR to HCP in a more restricted way. A more positive attitude towards vaccination also relates to fewer misconceptions. Occupational physicians' knowledge and attitude further influence the extent to which pregnant HCP receive vaccinations against influenza. Knowledge about official recommendations does not influence the recommendation of influenza vaccination for pregnant women. Conclusions: Reasons for vaccination gaps in HCP might have their roots in occupational physicians' incomplete knowledge of vaccination recommendations. Attitudes, which are related to misperceptions, also influence which vaccinations are recommended to HCP. Official recommendations, and not personal attitudes and misconceptions, should guide occupational vaccination behavior. © 2014 Elsevier Ltd. Source


Vorbrugg A.,Goethe University Frankfurt
Environment and Planning D: Society and Space | Year: 2015

Drawing on ethnographic research, this study analyzes the work of a German political foundation in Ukraine. Departing from a governmentality perspective that closely examines concrete practices, I focus on the organization’s attempts to establish itself as a political actor. This foundation aims to build more democratic political imaginations and open up different spaces for contestation. However, in both its rationalities and its practices, the foundation’s project also (re)inscribes enclosures. It is both reflective and productive of boundaries between those who qualify as full political subjects, and others who do not, and claims a preformed knowledge of democracy and civil society. In examining situated and ambivalent claims to democracy and civil society—on the level of practices and beyond ‘classic’ liberal contexts of governance—this paper demonstrates that studies of governmentality provide analytical tools to shed light on subjects that have gained little attention in the field so far. It further contributes to a deeper understanding of what kinds of publics and political realities emerge in projects of ‘actually existing democratization’. © 2015 pion and its Liscensors. Source


Evaluating the patient's individual bleeding history with a standardized questionnaire, using "point-of-careo" - methods for coagulation analyses and providing autologous transfusion techniques are preconditions of a modern coagulation management. Therapy of coagulopathic patients should be based on structured hemotherapy algorithms. Surgical haemostasis and the maintenance of the basic conditions for haemostasis are elementary requirements for an effective therapy. In cases of diffuse bleeding, early antifibrinolytic therapy should be considered. Coagulation factor deficiencies should be corrected "goal-directedo" using coagulation factor concentrates. Transfusion of fresh frozen plasma is only indicated in the clinical setting of massive transfusions. DDAVP and transfusion of platelet concentrates are options to optimize primary haemostasis. In cases of on-going bleeding, recombinant activated coagulation factor VII represents an option for "ultima- ratioo" therapy. © Georg Thieme Verlag KG Stuttgart • New York. Source


Piper R.C.,University of Iowa | Dikic I.,Goethe University Frankfurt | Lukacs G.L.,McGill University
Cold Spring Harbor Perspectives in Biology | Year: 2014

When ubiquitin (Ub) is attached to membrane proteins on the plasma membrane, it directs them through a series of sorting steps that culminate in their delivery to the lumen of the lysosome where they undergo complete proteolysis. Ubiquitin is recognized by a series of complexes that operate at a number of vesicle transport steps. Ubiquitin serves as a sorting signal for internalization at the plasma membrane and is the major signal for incorporation into intraluminal vesicles of multivesicular late endosomes. The sorting machineries that catalyze these steps can bind Ub via a variety of Ub-binding domains. At the same time, many of these complexes are themselves ubiquitinated, thus providing a plethora of potential mechanisms to regulate their activity. Here we provide an overview of how membrane proteins are selected for ubiquitination and deubiquitination within the endocytic pathway and how that ubiquitin signal is interpreted by endocytic sorting machineries. © 2014 Cold Spring Harbor Laboratory Press; all rights reserved. Source


Hummel T.,TU Dresden | Lotsch J.,Goethe University Frankfurt
Archives of Otolaryngology - Head and Neck Surgery | Year: 2010

Objective: To determine appropriate counseling of patients with olfactory dysfunction. Design: Retrospective analysis. Setting: Interdisciplinary Center for Smell and Taste, University of Dresden Medical School, Technical University of Dresden. Patients: A total of 361 males and 533 females, aged 11 to 84 years, who twice reported to the Interdisciplinary Center for Smell and Taste. Main Outcome Measures: Residual olfactory performance, duration of olfactory loss until first assessment, presence or absence of parosmia or phantosmia, origin of olfactory loss, interval between assessments, age, sex, and smoking habits. Results: Although 431 patients (48.2%) had functional anosmia at the first olfactory assessment, 444 (49.7%) had hyposmia, and 19 (2.1%) had normosmia; at the second assessment, 278 (31.1%) had functional anosmia, 496 (55.5%) had hyposmia, and 120 (13.4%) had normal olfactory function (P<.001). Changes in smell scores depended positively on the initial score and negatively on age and smoking habits. Normosmia was more likely to be restored in females and when residual olfactory function was relatively high. In contrast, the origin of dysfunction had no direct predictive value because it was mostly reflected by initial smell scores. However, in a sub-analysis omitting the initial olfactory performance as a potential predictor, the initial presence of parosmia was associated with a lower probability of anosmia as the final outcome. Conclusion: The prognosis of olfactory dysfunction mainly depends on residual function, sex, parosmia, smoking habits, and age, whereas in this statistical model, origin plays only a second-line role, reflected in different degrees of initial olfactory loss. ©2010 American Medical Association. All rights reserved. Source


Xia T.,Tsinghua University | He L.,Goethe University Frankfurt | Zhuang P.,Tsinghua University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2013

QCD at finite isospin chemical potential μI possesses a positively definite fermion determinant, and the lattice simulation can be successfully performed. While the two-flavor effective models may be sufficient to describe the phenomenon of pion condensation, it is interesting to study the roles of the strangeness degree of freedom and the UA(1) anomaly. In this paper, we present a systematic study of the three-flavor Nambu-Jona-Lasinio model with a Kobayashi-Maskawa-'t Hooft (KMT) term that mimics the U A(1) anomaly at finite isospin chemical potential. In the mean-field approximation, the model predicts a phase transition from the vacuum to the pion superfluid phase, which takes place at μI equal to the pion mass mπ. Due to the UA(1) anomaly, the strangeness degree of freedom couples to the light quark degrees of freedom and the strange quark effective mass depends on the pion condensate. However, the strange quark condensate and the strange quark effective mass change slightly in the pion superfluid phase, which verifies the validity of the two-flavor models. The effective four-fermion interaction of the Kobayashi-Maskawa-'t Hooft term in the presence of the pion condensation is constructed. Due to the UA(1) anomaly, the pion condensation generally induces scalar-pseudoscalar interaction. The Bethe-Salpeter equation for the mesonic excitations is established, and the meson mass spectra are obtained at finite isospin chemical potential and temperature. Finally, the general expression for the topological susceptibility χ at finite isospin chemical potential μI is derived. In contrast to the finite temperature effect which suppresses χ, the isospin density effect leads to an enhancement of χ. © 2013 American Physical Society. Source


Hinz O.,Goethe University Frankfurt | Spann M.,Ludwig Maximilians University of Munich
Decision Support Systems | Year: 2010

In Name-Your-Own-Price auctions (NYOP) prospective buyers bid against a secret reserve price set by the seller and only win the auction at the price of their bid if it is equal or higher than the seller's reserve price. Thus, bidders who want to win the auction without too much overbidding have a strong incentive to learn more about the seller's secret reserve price, possibly via their own network of friends, digital networks or online communities. Information sharing and information diffusion in digital networks can change bidding behavior and thus have important implications for sellers in NYOP markets. We develop a decision support system that enables sellers to assess the impact of information diffusion and to analyze the profitability of different seller strategies. We build the system from the bottom up by developing and testing a model of agents' bidding behavior which constitutes the basis for analyzing the effects of different network structures and seller strategies on profit. Sellers can react to information diffusion by setting the secret reserve price optimally, taking into account this strategic element by the provision of a forum and by decreasing the quality of information through forum intervention. Our results show that information diffusion can either decrease or increase seller profit depending on the buyers' initial beliefs about the seller's costs. We also show that the structure of the underlying social network is an important driver for information diffusion and that data about social networks might hence be of value to decision makers. © 2010 Elsevier B.V. All rights reserved. Source


Parzeller M.,Goethe University Frankfurt
Rechtsmedizin | Year: 2011

The actual age of individuals plays a substantial procedural role in very different legal fields, such as law concerning foreign nationals, criminal law, civil law and social law. Legal protective functions can exist due to the age of an individual, for example the application of juvenile criminal law or age can be the basis of a claim for state and social services. Claims for social services can be rejected if only certain age groups (e.g. minors) are eligible for these services. If the true age of an individual cannot be verified without any question of doubt, the question arises how forensic age diagnostics can contribute to solving the problem. Due to the nature of the methods used for forensic age diagnostics, such as radiological diagnostics, legal objections can be raised against using this method especially if unaccompanied and underage refugees are involved. Partially unclear legal requirements, contradictory jurisdiction as well as non-objective remarks in the lay press and of physician organizations do not contribute to the legal security of the examining expert. The present situation regarding the basis of authorization in connection with legal ordinance for X-ray examinations will be discussed taking the current jurisdiction and literature into account. © 2010 Springer-Verlag. Source


Liu F.,Chinese Academy of Geological Sciences | Gerdes A.,Goethe University Frankfurt | Liu P.,Chinese Academy of Geological Sciences
Gondwana Research | Year: 2012

A unique dissolution-reprecipitation zircon has been identified for the first time in a Qtz- and Phe-bearing eclogite from the drill hole CCSD-MH, southwestern Sulu UHP terrane by using laser Raman and cathodoluminescence (CL) imaging combined with trace-element analyses and U-Pb and Lu-Hf isotope data. Relic inherited domains of partially dissolved zircon show magmatic features and preserve mineral inclusions of Cpx+Pl+Qtz+Ap. Whereas newly formed zircons crystallized around or along cracks of the inherited (magmatic) domains and contain mineral inclusions of Coe+Grt+Omp+Phe+Ap typical for UHP metamorphism. In addition, primary fluid inclusions were identified in the coesite-bearing zircon domains, characterized by a single H 2O-phase or CO 2-H 2O-phase, indicating the presence of fluids during UHP conditions. Strongly dissolved inherited (magmatic) zircons yielded SHRIMP 206Pb/ 238U ages of 782-588Ma with an upper intercept age of 780±14Ma. New recrystallized or metamorphic zircons yielded consistent Triassic UHP ages around 238-225Ma with a weighted mean of 229.2±2.3Ma. Zircon trace element and Hf isotope compositions and mineral inclusions classify the protolith of the Sulu eclogite as an intermediate to mafic Neoproterozoic igneous rock, which was subducted to mantle depth and experienced UHP metamorphism in Middle Triassic times. The juvenile εHf (780Ma) value of+7.4±2.9 in inherited (magmatic) zircon points to a significant input from the depleted mantle to the Dabie-Sulu UHP terrane during Middle Neoproterozoic. New UHP zircon domains have low Lu/Hf, Th/U and significantly higher 176Hf/ 177Hf ratios than the inherited (magmatic) zircons, consistent with formation during recrystallization and fractionation of the Lu-Hf system during UHP metamorphism. © 2011 International Association for Gondwana Research. Source


Teschke R.,Goethe University Frankfurt | Lebot V.,CIRAD
Food and Chemical Toxicology | Year: 2011

Rare cases of hepatotoxicity emerged with the use of kava drugs and dietary supplements prepared from rhizomes and roots of the South Pacific plant kava (Piper methysticum). Their psychoactive, anxiolytic, relaxing, and recreational ingredients are the kavalactones kavain, dihydrokavain, methysticin, dihydromethysticin, yangonin, and desmethoxyyangonin, but there is little evidence that these kavalactones or the non-kavalactones pipermethystine and flavokavain B are the culprits of the adverse hepatic reactions. It rather appears that poor quality of the kava material was responsible for the liver toxicity. Analysis of existing kava quality standardizations with focus on chemical, agricultural, manufacturing, nutritional, regulatory, and legislation backgrounds showed major shortcomings that could easily explain quality problems. We therefore suggest a uniform, internationally accepted device for kava quality standardizations that are in the interest of the consumers because of safety reasons and will meet the expectations of kava farmers, pharmaceutical manufacturers, regulators of agencies, and legislators. The initial step resides in the establishment of Pan-Pacific kava quality legislation as an important part of the proposed Kava Quality Standardization Code. In conclusion, a sophisticated approach to establish kava quality standardizations is needed for safe human use of kava as relaxing traditional beverages, the anxiolytic drugs, and recreational dietary supplements. © 2011 Elsevier Ltd. Source


Muller J.,Goethe University Frankfurt
ChemPhysChem | Year: 2011

Fluctuations (or noise) are often merely considered a nuisance, an unwanted disturbance limiting the accuracy of a scientific measurement. Electronic fluctuations, however, reveal hidden pieces of information not present in the mean quantity (the resistance) itself. Herein we describe resistance noise spectroscopy as a powerful new tool for investigating the low-frequency dynamics of electronic processes in low-dimensional organic conductors. Over the years, these molecular charge-transfer complexes have provided unprecedented model systems for exploring the physics of low-dimensional materials. The combination of low dimensionality with other parameters, specific to molecular conductors, sets the stage for Coulomb correlation effects to become relevant and, under certain circumstances, even to dominate the properties of the π-electron system. The combined effects of strong electron-electron and electron-phonon interactions give rise to the rich phenomenology of ground states encountered in these materials. To provide examples, we describe noise spectroscopy as a method to study the coupling of the correlated charge carriers to intramolecular modes of lattice vibrations and to investigate the inhomogeneous coexistence region of antiferromagnetic (Mott) insulating and superconducting phases. Come on feel the noise: Fluctuation spectroscopy is described as a new tool to study the dynamics of charge carriers in organic conductors. In these materials the interplay of low dimensionality (see picture), strong electronic correlations and electron-lattice interactions give rise to a rich phenomenology of ground states. Intramolecular modes of lattice vibrations and the inhomogeneous coexistence region of antiferromagnetic (Mott) insulating and superconducting phases are discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Thromboembolism is a major complication in patients with ventricular assist devices (VADs). Drug anticoagulation and the use of biocompatible surfaces, such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin-induced thrombocytopenia (HIT) type II, mainly through heparin/platelet factor 4 (PF4) antibodies. We assessed the presence of PF4 antibodies in VAD thrombi of patients with heparin-coated VADs and HIT II. Thrombi (n = 6) were obtained from the replaced Excor ventricles of patients with HIT II after biventricular VAD implantation (Excor Adult; Berlin Heart, Germany). Excor ventricles were changed after clinical examination and suspicion of thrombi in the polyurethane valves. Expression of PF4- antibodies was assessed with the use of a polyclonal rabbit antibody (anti-PF4 antibody; Abcam, USA). Expression was assessed by 2 independent observers. Biopsies of all thrombi showed an extreme positive immunoreaction for PF4. No differences between the different thrombi and localization (left/right Excor ventricle) were observed. The thrombi were organized, without lamination of fibrin and cellular layers. Platelet surface expression of PF4 in the thrombi reflects HIT antigen presentation. The physical relationship between the PF4-positive thrombi and the heparin-coated surface suggests that onset of HIT II could be influenced by the immobilized heparin coating. Copyright © 2013 Elsevier Inc. All rights reserved. Source


Philipsen O.,Goethe University Frankfurt
Acta Physica Polonica B, Proceedings Supplement | Year: 2012

The present knowledge of the QCD phase diagram based on simulations of lattice QCD is summarised. The main questions are whether there is a critical point in the QCD phase diagram and whether it is related to a chiral phase transition. It is shown that QCD at imaginary chemical potentials has a rich phase structure, which can be determined in a controlled way without the sign problem and which severely constrains the phase structure at real chemical potentials. Source


Objective: The data of 69 cases of initially suspected black cohosh (BC)-induced liver disease were reviewed and analyzed to clarify whether BC hepatotoxicity really exists as a disease entity in these cases comparable to toxic liver disease being caused by various drugs and dietary supplements. Methods: The cases comprised 11 published case reports and 58 spontaneous reports to national regulatory agencies. The analysis includes assessment of causality for BC, data quality of the presented cases, and their inconsistencies and confounding variables. Results: The assessed data raise serious doubts on the initial claims of causality for BC in these cases and provide clear evidence of their poor quality, especially when spontaneous reports are considered. There are major inconsistencies for the same patient regarding reported data. Moreover, the analysis of all cases disclosed confounding variables. These include poor case data quality, uncertainty of BC product, quality, and identification, undisclosed indication, insufficient adverse event definition, lack of temporal association and dechallenge, missing or inadequate evaluation of alcohol use, comedication, comorbidity, reexposure test, and alternative diagnoses. Conclusions: The presented data do not support the concept of hepatotoxicity in a primarily suspected causal relationship to the use of BC and failure to provide a signal of safety concern, but further efforts have to be undertaken to dismiss or to substantiate the existence of BC hepatotoxicity as a special disease entity. The future strategy should be focused on prospective causality evaluations in patients diagnosed with suspected BC hepatotoxicity, using a structured, quantitative, and hepatotoxicity-specific causality assessment method. Copyright © 2010 The North American Menopause Society. Source


Rieger J.,Goethe University Frankfurt
Numerical Functional Analysis and Optimization | Year: 2011

Differential inclusions provide a suitable framework for modelling choice and uncertainty. In finite dimensions, the theory of ordinary differential inclusions and their numerical approximations is well-developed, whereas little is known for partial differential inclusions, which are the deterministic counterparts of stochastic partial differential equations. The aim of this article is to analyze strategies for the numerical approximation of the solution set of a linear elliptic partial differential inclusion. The geometry of its solution set is studied, numerical methods are proposed, and error estimates are provided. Copyright © Taylor & Francis Group, LLC. Source


Mantele W.,Goethe University Frankfurt
Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy | Year: 2015

Spectrochimica Acta A is open for a vivid exchange among scientists and fosters the open discussion of published papers. IR spectroscopy and UV-CD spectroscopy can be much more specific for the detection of protein conformational changes upon binding of a biologically active small molecule. However, both techniques need carefully selected experimental conditions and a thoughtful analysis of the data. It is also ignored by some instrument manufacturers that sell IR cells for this purpose and provide plug and play software for the spectral analysis. However, the attempt to provide a push-one-button-and-get-a-result-method has not proven successful up to now. Source


Blume C.,Goethe University Frankfurt
Acta Physica Polonica B | Year: 2012

Recent experimental findings on the properties of the chemical and kinetic freeze-out are reviewed, including data from low energies (SPS) over RHIC, up to recent results from the LHC. We discuss whether chemical freeze-out coincides with hadronization or if there is evidence for a "life after hadronization" which might significantly change particle abundances. Source


Korkusuz H.,Goethe University Frankfurt
Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance | Year: 2010

Because endomyocardial biopsy has low sensitivity of about 20%, it can be performed near to myocardium that presented as late gadolinium enhancement (LGE) in cardiovascular magnetic resonance (CMR). However the important issue of comparing topography of CMR and histological findings has not yet been investigated. Thus the current study was performed using an animal model of myocarditis. In 10 male Lewis rats experimental autoimmune myocarditis was induced, 10 rats served as control. On day 21 animals were examined by CMR to compare topographic distribution of LGE to histological inflammation. Sensitivity, specificity, positive and negative predictive values for LGE in diagnosing myocarditis were determined for each segment of myocardium. Latter diagnostic values varied widely depending on topographic distribution of LGE and inflammation as well as on the used CMR sequence. Sensitivity of LGE was up to 76% (left lateral myocardium) and positive predictive values were up to 85% (left lateral myocardium), whereas sensitivity and positive predictive value dropped to 0-33% (left inferior myocardium). Topographic distribution of LGE and histological inflammation seem to influence sensitivity, specificity, positive and negative predictive values. Nevertheless, positive predictive value for LGE of up to 85% indicates that endomyocardial biopsy should be performed "MR-guided". LGE seems to have greater sensitivity than endomyocardial biopsy for the diagnosis of myocarditis. Source


Giacosa F.,Goethe University Frankfurt
Progress in Particle and Nuclear Physics | Year: 2012

Recent advances in the development of a chiral linear σ-model with (axial-)vector mesons are presented. The model is based on the basic requirements of global chiral symmetry and dilatation invariance. The role of (axial-)vector states turns out to be crucial both in the meson and the baryon sectors. First results at non-zero temperature and density are discussed. © 2012 Elsevier B.V. All rights reserved. Source


We present the production cross section of electrons from heavy-flavour hadron decays measured at mid-rapidity (|η| < 0.8) with ALICE in protonproton collisions at √s = 7 TeV. The contribution from pure beauty decays is identified using the electron displacement from the interaction vertex. The results are compared to FONLL calculations and used as pp reference for Pb-Pb collisions after scaling to the same centre-of-mass energy. In Pb-Pb collisions at √s NN = 2.76 TeV, the inclusive electron spectrum is measured at mid-rapidity for different centrality classes and compared to a cocktail of background electrons. The corresponding nuclear modification factor of cocktail-subtracted electrons indicates heavy-flavour suppression by a factor 1.5-5 at high p T in most central Pb-Pb collisions. Source


Arend A.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2013

The measurement of decay products from rare particles in the CBM experiment defines the requirements for the used detector systems. This report describes the approaches for the Transition Radiation Detector to fulfil these requirements and presents the current status of the prototype development. First results from beam tests with these prototypes are discussed. Source


The genome sequence of Haloferax volcanii is available and several comparative genomic in silico studies were performed that yielded novel insight for example into protein export, RNA modifications, small non-coding RNAs, and ubiquitin-like Small Archaeal Modifier Proteins. The full range of functional genomic methods has been established and results from transcriptomic, proteomic and metabolomic studies are discussed. Notably, Hfx. volcanii is together with Halobacterium salinarum the only prokaryotic species for which a translatome analysis has been performed. The results revealed that the fraction of translationally-regulated genes in haloarchaea is as high as in eukaryotes. A highly efficient genetic system has been established that enables the application of libraries as well as the parallel generation of genomic deletion mutants. Facile mutant generation is complemented by the possibility to culture Hfx. volcanii in microtiter plates, allowing the phenotyping of mutant collections. Genetic approaches are currently used to study diverse biological questionsfrom replication to posttranslational modificationand selected results are discussed. Taken together, the wealth of functional genomic and genetic tools make Hfx. volcanii a bona fide archaeal model species, which has enabled the generation of important results in recent years and will most likely generate further breakthroughs in the future. © 2011 Jrg Soppa. Source


Lanzendorf M.,Goethe University Frankfurt
International Journal of Sustainable Transportation | Year: 2010

Over the last few years, travel-behavior researchers have generally acknowledged the importance of habits and key events in understanding travel-behavior changes. The purpose of this study is to contribute to the evolving research field of mobility biographies. With a retrospective, qualitative survey, 20 parents of small children are questioned about key events affecting their travel behavior and in particular the role of childbirth in this respect. The findings reveal that the commonly expected car-dependency after childbirth is only one pattern among others such as the stability or even increase of green mode use. © Taylor & Francis Group, LLC. Source


Pfeiffer A.N.,ETH Zurich | Cirelli C.,ETH Zurich | Smolarski M.,ETH Zurich | Dorner R.,Goethe University Frankfurt | Keller U.,ETH Zurich
Nature Physics | Year: 2011

The timing of electron release in strong-field double ionization poses great challenges both for conceptual definition and for conducting experimental measurements. Here we present coincidence momentum measurements of the doubly charged ion and of the two electrons arising from double ionization of argon using elliptically polarized laser pulses. Based on a semi-classical model, the ionization times are calculated from the measured electron momenta across a large intensity range. This paper discusses how this method provides timings on a coarse and on a fine scale, similar to the hour and the minute hand of a clock. We found that the ionization time of the first electron is in good agreement with the simulation, whereas the ionization of the second electron occurs significantly earlier than predicted. Source


Sabah C.,Goethe University Frankfurt
Progress In Electromagnetics Research B | Year: 2010

Novel, dual-band, single and double negative metamaterials composed of nonconcentric and different sized delta loop resonators are presented. The proposed structures provide two distinct resonant frequencies in the microwave region. Effective medium parameters of these metamaterial structures are extracted using retrieval method to demonstrate the presence of the mentioned frequencies. In addition, equivalent circuit model for the individual magnetic resonator and wire strip is presented to give a clear explanation for the resonance behavior of the structures and to validate the proposed designs. The results show that the proposed metamaterials can be used as an alternative to the known counterparts especially when a dual-band operation is needed at the frequency region of interest. Source


Friedrich A.,Goethe University Frankfurt
Journal of physics. Condensed matter : an Institute of Physics journal | Year: 2012

The high-pressure behaviour of Bi2Fe4O9 was analysed by in situ powder and single-crystal x-ray diffraction and Raman spectroscopy. Pressures up to 34.3(8) GPa were generated using the diamond anvil cell technique. A reversible phase transition is observed at approximately 6.89(6) GPa and the high-pressure structure is stable up to 26.3(1) GPa. At higher pressures the onset of amorphization is observed. The crystal structures were refined from single-crystal data at ambient pressure and pressures of 4.49(2), 6.46(2), 7.26(2) and 9.4(1) GPa. The high-pressure structure is isotypic to the high-pressure structure of Bi2Ga4O9. The lower phase transition pressure of Bi2Fe4O9 with respect to that of Bi2Ga4O9 (16 GPa) confirms the previously proposed strong influence of cation substitution on the high-pressure stability and the misfit of Ga3+ and Fe3+ in tetrahedral coordination at high pressure. A fit of a second-order Birch-Murnaghan equation of state to the p-V data results in K0 = 74(3) GPa for the low-pressure phase and K0 = 79(2) GPa for the high-pressure phase. The mode Grüneisen parameters were obtained from Raman-spectroscopic measurements. Source


Halfon P.,Virological Departement Laboratoire Alphabio | Sarrazin C.,Goethe University Frankfurt
Liver International | Year: 2012

Recent advances in molecular biology have led to the development of novel small molecules that target specific viral proteins of the hepatitis C virus (HCV) life cycle. These drugs, collectively termed directly acting antivirals (DAA), include a range of non-structural (NS) 3/NS4A protease, NS5B polymerase and NS5A inhibitors at various stages of clinical development. Some others drugs called 'non DAA'or indirect inhibitors are not focused on one site of the life cycle target and are still in early pre-clinical and clinical phase I, II and III trials. The rapid replication rate of HCV, along with the low fidelity of its polymerase, results in a generation of mutations throughout the viral genome and sequence variation in the HCV population known as a quasispecies. The efficacy of DAA is limited by the presence of these mutations, resulting in amino acid substitutions within the targeted proteins which affect viral sensitivity to these compounds. Thus, attributable to the high genetic variability of HCV, variants with reduced susceptibility to DAA can occur naturally even before treatment begins, but usually at low levels. Thus it is not surprising that these changes are selected in patients that either breakthrough or do not respond to potent DAA treatment. Six major position mutations in the NS3 HCV Protease (36, 54, 155, 156, 168 and 170), fifteen in the NS5B polymerase (96, 282, 316, 365, 414, 419, 423, 448, 482, 494, 495, 496, 499, 554, 559) and five in the NS5 A region (28, 30, 31, 58 and 93) have now been reported in vitro or in vivo associated with different levels of resistance. The amino acid composition at several of the drug resistance sites can vary between the HCV genotypes/subtypes, resulting in different consensus amino acids leading to a reduction in replicative fitness as well as reduced DAA and non- DAA sensitivity. Information on patterns of resistance to and cross resistance between antiviral agents is increasingly available and may be important for decisions on how to combine drugs to achieve an optimum antiviral effect. This review debates the clinical relevance of resistance to direct and indirect inhibitors taking into account the future potential therapeutic strategies to help patients who do develop resistance to HCV inhibitors. Finally, this chapter treats two points of view: 'for' and 'against' the question of the importance of resistance. © 2012 John Wiley & Sons A/S. Source


Seifert V.,Goethe University Frankfurt
Acta neurochirurgica. Supplement | Year: 2011

The extent of resection marks one prognostic factor for patients with malignant gliomas. Among the methods used for the intraoperative control of the extent of resection, intraoperative magnetic resonance imaging (ioMRI) has become a very attractive method. It was introduced in the in the final decade of the last century. The first available system was a low magnetic field strength unit employing 0.5 Tesla (T). While currently high-field systems (1.5 T and above) are being developed, different low-field ioMRI systems (0.5 T and below) have been used for brain tumor resection in far more centers than high-field ioMRI, corresponding to a greater number of publications. Undoubtedly, high-field ioMRI systems offer superior image quality and faster acquisition times. Yet, low-field ioMRI has influenced intraoperative decision-making and improved brain tumor resection. With this article, we review the use of low-field ioMRI in glioma surgery. Source


The objective of this study was to elucidate molecular mechanisms behind the antitumor activities of the isothiocyanate sulforaphane (SFN) in colorectal cancer cells. Cell growth was determined by BrdU incorporation and crystal violet staining. Protein levels were examined by Western blot analysis. Ornithine decarboxylase (ODC) activity was assayed radiometrically. Reverse transcriptase-PCR was used for measuring mRNA expression. For reporter gene assays plasmids were transfected into cells via lipofection and luciferase activity was measured luminometrically. Acetyl-histone H3 and H4 chromatin immunoprecipitation (ChIP) assays were performed followed by PCR with TGF-β-receptor II promoter specific primers. We could show that SFN-mediated cell growth inhibition closely correlates with a dose-dependent reduction of protein expression and enzymatic activity of ODC. This effect seems to be due to reduced protein levels and transactivation activity of transcription factor c-myc, a direct regulator of ODC expression, as a consequence of SFN-induced TGF-β/Smad signaling. The coherency of these results was further confirmed by using TGF-β receptor kinase inhibitor SB431542, which largely abolishes inhibitory effects of SFN on both, ODC activity and cell growth. Since elevated ODC enzyme activity is associated with enhanced tumor development, SFN may be a dietary phytochemical with potential to prevent carcinogenesis. Source


Lehrnbecher T.,Goethe University Frankfurt | Groll A.H.,University of Munster
Pediatric Blood and Cancer | Year: 2010

Invasive fungal infections are a major cause of morbidity and mortality in children with hematological malignancies and those undergoing allogeneic hematopoietic stem-cell transplantation (HSCT). Although several new antifungal compounds recently became available, some are not yet approved for the use in the pediatric population. Among the new class of echinocandins, micafungin has been licensed in Europe and Japan for children including neonates. Because micafungin is well tolerated and exhibits few clinical relevant drug-drug interactions, the compound is of particular interest for prophylaxis and treatment of invasive mycoses in pediatric patients with cancer or following allogeneic HSCT. This review will focus on the currently available pediatric data of micafungin with emphasis on pharmacokinetics, efficacy, and safety. © 2010 Wiley-Liss, Inc. Source


Ohlendorf D.,Goethe University Frankfurt
Zentralblatt fur Arbeitsmedizin, Arbeitsschutz und Ergonomie | Year: 2015

Mechanical stimuli, often in the form of physical activity, have a significant impact on bone density as they are assumed to have an osteogenic effect. The bone is built up and increases in firmness as soon as it is subjected to adequate loads, whereas bone density decreases (law of transformation of bone) with inactivity. This is best achieved when the sports discipline contains high peak loads in variable activities, integrated load switching, strength training and recovery phases. © 2015, Springer-Verlag Berlin Heidelberg. Source


Messerschmidt C.M.,Goethe University Frankfurt | Hinz O.,TU Darmstadt
Journal of Strategic Information Systems | Year: 2013

Grid computing can meet computational demands and offers a promising resource utilization approach. However, little research details the drivers of and obstacles to adoption of this technology. Institutional and organizational capability theory suggests an adoption model that accounts for inter- and intra-organizational influences. An empirical study with 233 high-ranking IT executives reveals that adoption results from social contagion, while organizational capabilities such as trust, firm innovativeness, tendency to outsource, and IT department size, influence adoption from an intra-organizational perspective. The findings show that mimetic pressures and trust play major roles in adoption processes, which differentiates grid computing from other inter-organizational systems. © 2013 Elsevier B.V. All rights reserved. Source


Krause P.K.,Goethe University Frankfurt
Computers and Graphics (Pergamon) | Year: 2010

This paper presents new fixed-rate texture compression systems for RGB and RGBA images, which use variable precision differential encoding for the color codewords, resulting in reduced compression artifacts, in particular for smooth color variations. Experiments using hundreds of textures show that they achieve higher quality than the commonly used S3TC at the same compression ratio or (for RGBA images) similar quality to S3TC at twice the compression ratio. In hardware implementations a large part of decompression hardware can be shared with existing common systems, minimizing the amount of additional hardware needed. © 2010 Elsevier B.V. All rights reserved. Source


Zagrebaev V.I.,Joint Institute for Nuclear Research | Greiner W.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2011

The problem of production and study of heavy neutron-rich nuclei has been intensively discussed during recent years. Many reasons arouse a great interest in this problem. The present limits of the upper part of the nuclear map are very close to the β stability line while the unexplored area of heavy neutron-rich nuclides (also those located along the neutron closed shell N=126 to the right-hand side of the stability line) is extremely important for nuclear astrophysic investigations and, in particular, for the understanding of the r process of astrophysical nucleogenesis. For elements with Z100 only neutron deficient isotopes (located to the left of the stability line) have been synthesized so far. The "northeast" area of the nuclear map can be reached neither in fusion-fission reactions nor in fragmentation processes widely used nowadays for the production of new nuclei. Multinucleon transfer processes in near barrier collisions of heavy (and very heavy, U-like) ions seem to be the only reaction mechanism allowing us to produce and explore neutron-rich heavy nuclei including those located at the superheavy island of stability. In this paper several transfer reactions for different projectile-target combinations are studied in detail. Besides the predictions for the cross sections of such processes, we also analyze the angular and energy distributions of primary and survived reaction products in the laboratory frame. These results, as well as predicted excitation functions for the yields of neutron-rich superheavy isotopes, might be useful for the design of appropriate experimental equipment and for carrying out experiments of such kind. © 2011 American Physical Society. Source


Nicolini P.,Goethe University Frankfurt | Rinaldi M.,University of Geneva
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In this Letter we study the radiation measured by an accelerated detector, coupled to a scalar field, in the presence of a fundamental minimal length. The latter is implemented by means of a modified momentum space Green's function. After calibrating the detector, we find that the net flux of field quanta is negligible, and that there is no Planckian spectrum. We discuss possible interpretations of this result, and we comment on experimental implications in heavy ion collisions and atomic systems. © 2010 Elsevier B.V. Source


Nicolini P.,Goethe University Frankfurt | Spallucci E.,University of Trieste
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2011

In this Letter, we propose a new scenario emerging from the conjectured presence of a minimal length ℓ in the spacetime fabric, on the one side, and the existence of a new scale invariant, continuous mass spectrum, of un-particles on the other side. We introduce the concept of un-spectral dimension DU of a d-dimensional, euclidean (quantum) spacetime, as the spectral dimension measured by an "un-particle" probe. We find a general expression for the un-spectral dimension DU labelling different spacetime phases: a semi-classical phase, where ordinary spectral dimension gets contribution from the scaling dimension dU of the un-particle probe; a critical "Planckian phase", where four-dimensional spacetime can be effectively considered two-dimensional when dU=1; a "Trans-Planckian phase", which is accessible to un-particle probes only, where spacetime as we currently understand it looses its physical meaning. © 2010 Elsevier B.V. Source


Muranyi W.,University of Heidelberg | Malkusch S.,University of Wurzburg | Muller B.,University of Heidelberg | Heilemann M.,Goethe University Frankfurt | And 2 more authors.
PLoS Pathogens | Year: 2013

The inner structural Gag proteins and the envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) traffic independently to the plasma membrane, where they assemble the nascent virion. HIV-1 carries a relatively low number of glycoproteins in its membrane, and the mechanism of Env recruitment and virus incorporation is incompletely understood. We employed dual-color super-resolution microscopy visualizing Gag assembly sites and HIV-1 Env proteins in virus-producing and in Env expressing cells. Distinctive HIV-1 Gag assembly sites were readily detected and were associated with Env clusters that always extended beyond the actual Gag assembly site and often showed enrichment at the periphery and surrounding the assembly site. Formation of these Env clusters depended on the presence of other HIV-1 proteins and on the long cytoplasmic tail (CT) of Env. CT deletion, a matrix mutation affecting Env incorporation or Env expression in the absence of other HIV-1 proteins led to much smaller Env clusters, which were not enriched at viral assembly sites. These results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env(ΔCT) appears to be randomly incorporated. The observed Env accumulation surrounding Gag assemblies, with a lower density on the actual bud, could facilitate viral spread in vivo. Keeping Env molecules on the nascent virus low may be important for escape from the humoral immune response, while cell-cell contacts mediated by surrounding Env molecules could promote HIV-1 transmission through the virological synapse. © 2013 Muranyi et al. Source


Kuhl H.,Goethe University Frankfurt | Schneider H.P.G.,University of Munster
Climacteric | Year: 2013

Based on the results of a French cohort of postmenopausal women, it has been claimed that micronized progesterone does not enhance breast cancer risk. The impact of reproductive factors on breast cancer risk and a high prevalence of occult breast carcinomas at the time of menopause suggest an involvement of endogenous progesterone in the development of breast cancer. High mammographic density in the luteal phase and during treatment with estrogen/progestogen combinations reflect a change in the composition of mammary stroma and an increased water accumulation in the extracellular matrix which is caused by hygroscopic hyaluronan-proteoglycan aggregates. Proteoglycans are also involved in the regulation of proliferation, migration, and differentiation of epithelial cells and angiogenesis, and may influence malignant transformation of breast cells and progression of tumors. Reports on a lack of effect of estrogen/progesterone therapy on breast cancer risk may be rooted in a selective prescription to overweight women and/or to the very low progesterone serum levels after oral administration owing to a strong inactivation rate. The contradictory results concerning the proliferative effect of progesterone may be associated with a different local metabolism in normal compared to malignant breast tissue. Similar to other progestogens, hormone replacement therapy with progesterone seems to promote the development of breast cancer, provided that the progesterone serum levels have reached the threshold for endometrial protection. © 2013 International Menopause Society. Source


Schmeling H.,Goethe University Frankfurt
Tectonophysics | Year: 2010

Active or passive continental rifting is associated with thinning of the lithosphere, ascent of the asthenosphere, and decompressional melting. This melt may percolate within the partially molten source region, accumulate and be extracted. Two-dimensional numerical models of extension of the continental lithosphere-asthenosphere system are carried out using an Eulerian visco-plastic formulation. The equations of conservation of mass, momentum and energy are solved for a multi-component (crust-mantle) and two-phase (solid-melt) system. Temperature-, pressure-, and stress-dependent rheologies based on laboratory data for granite, pyroxenite and olivine are used for the upper and lower crust, and mantle, respectively. Rifting is modelled by externally prescribing a constant rate of widening with velocities between 2.5 and 40 mm/yr. A typical extension experiment is characterized by 3 phases: 1) distributed extension, with superimposed pinch and swell instability, 2) lithospheric necking, 3) continental break up, followed by oceanization. The timing of the transition from stages 1) to 2) depends on the presence and magnitude of a localized perturbation, and occurs typically after 100-150 km of total extension for the lithospheric system studied here. This necking phase is associated with a pronounced negative topography ("rift valley") and a few 100 m of rift flanks. The dynamic part of this topography amounts to about 1 km positive topography. This means, if rifting stops (e.g. due to a drop of external forces), immediate additional subsidence by this amount is predicted. Solidification of ascended melt beneath rift flanks leads to basaltic enrichment and underplating beneath the flanks, often observed at volcanic margins. After continental break up, a second time-dependent upwelling event off the rift axis beneath the continental margins is found, producing further volcanics. Melting has almost no or only a small accelerating effect on the local extension value (β-value) for a constant external extension rate. Melting has an extremely strong effect on the upwelling velocity within asthenospheric wedge beneath the new rift. This upwelling velocity is only weakly dependent on the rifting velocity. The melt induced sublithospheric convection cell is characterized by downwelling flow beneath rift flanks. Melting increases the topography of the flanks by 100-200 m due to depletion buoyancy. Another effect of melting is a significant amplification of the central subsidence due to an increase in localized extension/subsidence. Modelled magma amounts are smaller than observed for East African Rift System. Increasing the mantle temperature, as would be the case for a large scale plume head, better fits the observed magma volumes. If extension stops before a new ocean is formed, melt remains present, and convection remains active for 50-100 Myr, and further subsidence is significant. © 2009 Elsevier B.V. All rights reserved. Source


Brandt U.,Goethe University Frankfurt | Brandt U.,Radboud University Nijmegen
Angewandte Chemie - International Edition | Year: 2013

Inner workings: The X-ray crystal structure of the entire bacterial complex I at 3.3 Å resolution offers fascinating insights into a giant 536 kDa molecular machine. The respiratory chain complex seems to employ unique mechanisms of energetic coupling that are entirely different from those found in all other enzymes using redox energy to drive vectorial proton transport across a bioenergetic membrane. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


BACKGROUND:: The effect of alcohol consumption on inflammatory state and outcome in brain-injured patients remains controversial. We analyzed the influence of positive blood alcohol concentration (BAC) on inflammatory changes, in-hospital complications, and mortality in traumatic brain injury (TBI)-patients. PATIENTS/METHODS:: Patients with an Injury Severity Score (ISS)?≥?16 and Abbreviated Injury Scale of head (AIS-head) ≥ 3 were included upon arrival in the emergency room and grouped according to positive BAC (>0.5‰, BAC) vs.? Source


Fulda S.,Goethe University Frankfurt
Drug Discovery Today | Year: 2010

Resveratrol, a naturally derived stilbene that exists in various foods and beverages, has attracted increasing attention over the past decade because of its multiple beneficial properties, including chemopreventive and antitumor activities. There are several other natural derivatives of resveratrol that are structurally similar to resveratrol and are also present in food. In addition, a series of resveratrol analogs have been synthesized by the addition of defined functional groups to increase the potency and/or enhance the activity of specific properties of resveratrol. Such resveratrol derivatives might provide promising tools as cancer chemopreventive agents, as well as cancer therapeutics in the prevention and treatment of cancer. This review provides an overview of key derivatives of resveratrol as cancer therapeutics. © 2010 Elsevier Ltd. Source


Teilab K.,Goethe University Frankfurt
International Journal of Modern Physics A | Year: 2011

We report on the exclusive production of ω and η mesons in p + p reactions at 3.5 GeV beam kinetic energy. Production cross sections, angular distributions and Dalitz plots of both mesons were determined. Moreover, the relative contribution of the N(1535) resonance in η production at this energy was evaluated. We conclude that η mesons produced via N(1535) exihibit an isotropic angular distribution, whereas those produced directly show a strong anisotropic distribition. ω mesons show a slightly anisotropic angular distribition. © 2011 World Scientific Publishing Company. Source


Cancellous bone is frequently used for filling bone defects in a clinical setting. It provides favourable conditions for regenerative cells such as MSC and early EPC. The combination of MSC and EPC results in superior bone healing in experimental bone healing models. Materials and We investigated the influence of osteogenic culture conditions on the endothelial properties of early EPC and the osteogenic properties of MSC when cocultured on cancellous bone. Additionally, cell adhesion, metabolic activity, and differentiation were assessed 2, 6, and 10 days after seeding. The number of adhering EPC and MSC decreased over time; however the cells remained metabolically active over the 10-day measurement period. In spite of a decline of lineage specific markers, cells maintained their differentiation to a reduced level. Osteogenic stimulation of EPC caused a decline but not abolishment of endothelial characteristics and did not induce osteogenic gene expression. Osteogenic stimulation of MSC significantly increased their metabolic activity whereas collagen-1α and alkaline phosphatase gene expressions declined. When cocultured with EPC, MSC's collagen-1α gene expression increased significantly. EPC and MSC can be cocultured in vitro on cancellous bone under osteogenic conditions, and coculturing EPC with MSC stabilizes the latter's collagen-1α gene expression. Source


Marquardt N.,Goethe University Frankfurt
Environment and Planning D: Society and Space | Year: 2016

This paper focuses on the controversy over nationwide homeless statistics in Germany and uses the conflict as a window through which to explore the spatial and historical ontology of political numbers. Since the 1980s, the German national government's refusal to collect statistical data on homelessness has pushed homeless advocates to fight for quantitative assessments of homelessness as a crucial form of recognition. The conflict has produced a series of studies concerned with the practicability of homeless statistics. These studies offer an insight into the critical relations between space and calculation and the governmental problematizations of calculable territory and populations. Problematizations of space in feasibility studies reflect how the phenomenon of homelessness is not only a social issue ignored by governmental knowledge production, but a real obstacle to conventional ways of data collection on the population. To analyse the controversy and the difficulties of establishing homeless statistics, the paper combines theoretical reflections on the relations between numbers and politics and on spaces of calculation with more recent attempts to highlight the political nature of ignorance. The paper argues that the difficulties to count homeless people represent a case of ‘ontological ignorance’ connected to modern sedentariness. © 2015, © The Author(s) 2015. Source


Wacker M.,Goethe University Frankfurt
International Journal of Pharmaceutics | Year: 2013

Nanodispersed drug delivery systems for the intravenous injection have successfully overcome the hurdle of drug approval in the European Union and the United States. Although there is a need for highly advanced nanocarrier devices they have not been the result of a rational formulation design but were developed as stand-alone products in a long chain of case-by-case studies. This review focuses on aspects in development, composition, and manufacture of these innovative dosage forms that are relevant for the translation into new drug products. © 2013 Elsevier B.V. All rights reserved. Source


Sassenhagen J.,University of Marburg | Sassenhagen J.,Goethe University Frankfurt | Bornkessel-Schlesewsky I.,University of Marburg | Bornkessel-Schlesewsky I.,University of South Australia
Cortex | Year: 2015

When, during language processing, a reader or listener is confronted with a structurally deviant phrase, this typically elicits a late positive ERP deflection (P600). The P600 is often understood as a correlate of structural analysis. This assumption has informed a number of neurocognitive models of language. However, the P600 strongly resembles the P3, likely a more general electrophysiological correlate of reorientation behaviour supported by noradrenergic input to the ventral attention network/VAN. Some researchers have proposed that the P600 is an instance of the P3, not a distinct component reflecting the analysis of structured inputs. Here, we tested the P600-as-P3 hypothesis by estimating the alignment of the P600 elicited in a visual sentence processing task to simultaneously collected behavioural measures. A similar analysis was undertaken for a P3 elicited in a separate non-linguistic (face detection) task. Since the P3 is usually aligned to reaction time/RT, the same should hold for the P600; a failure to find RT alignment of the P600 would pose a problem for the P600-as-P3 hypothesis. In contrast, RT alignment of the P600 would associate it with the well-established VAN/Locus Coeruleus - Noradrenaline - Network subserving cortical reorientation.We failed to falsify the hypothesis of RT alignment. Secondary measures, while less unambiguous, were more in agreement with the P600-as-P3 hypothesis. We interpret our results as corroborating the hypothesis that the P600 is a P3, in that it shows that the P600 is RT-aligned. This perspective is unpredicted by an account of the P600 as indexing high-level processing. © 2015 Elsevier Ltd. Source


Diener H.-C.,University of Duisburg - Essen | Foerch C.,Goethe University Frankfurt | Riess H.,University Medicine Berlin | Rother J.,Stroke Unit and Intensive Care Unit | And 2 more authors.
The Lancet Neurology | Year: 2013

Systemic thrombolysis with alteplase is the only approved medical treatment for patients with acute ischaemic stroke. Thrombectomy is also increasingly used to treat proximal occlusions of the cerebral arteries, but has not shown superiority over systemic thrombolysis with alteplase. Many patients with acute ischaemic stroke are pretreated with antiplatelet or anticoagulant drugs, which can increase the bleeding risk of thrombolysis or thrombectomy. Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomised trials with no effect on clinical outcome, and the risk of intracerebral haemorrhage is increased with the combination of aspirin and clopidogrel. Antiplatelet drugs should not be given in the first 24 h after alteplase treatment. Data from pooled randomised trials and a large observational study show that thrombolysis can probably be done safely in patients given vitamin-K antagonists if the international normalised ratio is less than 1·7, although bleeding risk is slightly raised. Almost no data are available for the safety of alteplase in patients with atrial fibrillation who have been given novel oral anticoagulants (NOAC) for stroke prevention. Some coagulation parameters could help to identify patients treated with NOAC who might be eligible for thrombolysis. Thrombectomy can be done in patients given antiplatelets and probably in those given anticoagulants; however, conclusions about anticoagulants are based on findings from observational studies with small patient numbers. © 2013 Elsevier Ltd. Source


Behrens F.,Goethe University Frankfurt
Arthritis care & research | Year: 2013

To determine the "real-world" clinical effectiveness and safety of leflunomide in patients with psoriatic arthritis (PsA). This prospective, multinational 24-week observational study involved adult patients with active PsA who initiated treatment with leflunomide. Patients were evaluated at baseline, 12 weeks, and 24 weeks. The primary outcome was response as assessed by the Psoriatic Arthritis Response Criteria (PsARC) in patients with pre- and posttreatment data. A modified PsARC response analysis included patients with joint counts, but no severity scores. Other effectiveness evaluations included global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. All patients were evaluated for safety. A total of 514 patients were enrolled in this study (mean age 50.7 years, mean disease duration 6.1 years). In the primary effectiveness analysis, 380 (86.4%) of 440 patients (95% confidence interval 82.8%-89.4%) achieved a PsARC response at 24 weeks. Significant improvements were observed in tender and swollen joint scores and counts, patient and physician global assessments, fatigue, pain, skin disease, dactylitis, and nail lesions. The discontinuation rate was 12.3%. Ninety-eight adverse drug reactions occurred in 62 (12.1%) patients; 3 drug reactions were serious (2 increased liver enzymes, 1 hypertensive crisis). Leflunomide is an effective and well-tolerated option for PsA in daily clinical practice, with beneficial effects on peripheral arthritis and on other PsA manifestations, including pain, fatigue, dactylitis, and skin disease. Copyright © 2013 by the American College of Rheumatology. Source


Helmke C.,Goethe University Frankfurt
Cell Research | Year: 2016

Upon interaction of the CD95 receptor with its ligand, sequential association of the adaptor molecule FADD (MORT1), pro-forms of caspases-8/10, and the caspase-8/10 regulator c-FLIP leads to the formation of a death-inducing signaling complex. Here, we identify polo-like kinase (Plk) 3 as a new interaction partner of the death receptor CD95. The enzymatic activity of Plk3 increases following interaction of the CD95 receptor with its ligand. Knockout (KO) or knockdown of caspase-8, CD95 or FADD prevents activation of Plk3 upon CD95 stimulation, suggesting a requirement of a functional DISC for Plk3 activation. Furthermore, we identify caspase-8 as a new substrate for Plk3. Phosphorylation occurs on T273 and results in stimulation of caspase-8 proapoptotic function. Stimulation of CD95 in cells expressing a non-phosphorylatable caspase-8-T273A mutant in a rescue experiment or in Plk3-KO cells generated by CRISPR/Cas9 reduces the processing of caspase-8 prominently. Low T273 phosphorylation correlates significantly with low Plk3 expression in a cohort of 95 anal tumor patients. Our data suggest a novel mechanism of kinase activation within the Plk family and propose a new model for the stimulation of the extrinsic death pathway in tumors with high Plk3 expression.Cell Research advance online publication 21 June 2016; doi:10.1038/cr.2016.78. © 2016 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences Source


Brandt U.,Goethe University Frankfurt
Biochimica et Biophysica Acta - Bioenergetics | Year: 2011

Despite its central function in oxidative phosphorylation, the molecular mechanism of proton pumping respiratory complex I is still elusive. In recent years, considerable progress has been made towards understanding structure/function relationships in this very large and complicated membrane protein complex. Last year X-ray crystallographic analysis of bacterial and mitochondrial complex I provided important insights into its molecular architecture. Based on this evidence, here a hypothetical molecular mechanism for redox-driven proton pumping of complex I is proposed. According to this mechanism, two pump modules are driven by two conformational strokes that are generated by stabilization of the anionic forms of semiquinone and ubiquinol that are formed in the peripheral arm of complex I during turnover. This results in the experimentally determined pumping stoichiometry of 4 H +/2e -. In the two-state model, electron transfer from iron-sulfur cluster N2 is allowed only in the 'E-state,' while protonation of the substrate is only possible in the stabilizing 'P-state.' In the membrane arm, transition from the E- to the P-state drives the two pump modules via long range conformational energy transfer through the recently discovered helical transmission element connecting them. The proposed two-state stabilization-change mechanism is fully reversible and thus inherently explains the operation of complex I in forward and reverse mode. This article is part of a Special Issue entitled Allosteric cooperativity in respiratory proteins. © 2011 Elsevier B.V. All rights reserved. Source


Hartenfeller M.,Goethe University Frankfurt
Methods in molecular biology (Clifton, N.J.) | Year: 2011

Computer-assisted molecular design supports drug discovery by suggesting novel chemotypes and compound modifications for lead structure optimization. While the aspect of synthetic feasibility of the automatically designed compounds has been neglected for a long time, we are currently witnessing an increased interest in this topic. Here, we review state-of-the-art software for de novo drug design with a special emphasis on fragment-based techniques that generate druglike, synthetically accessible compounds. The importance of scoring functions that can be used to predict compound reactivity and potency is highlighted, and several promising solutions are discussed. Recent practical validation studies are presented that have already demonstrated that rule-based fragment assembly can result in novel synthesizable compounds with druglike properties and a desired biological activity. Source


Schwalbe H.,Goethe University Frankfurt
Structure | Year: 2011

Two recent studies by the Carlomagno/Pillai labs (Simon et al., 2011) and the Patel group (Tian et al., 2011) report the structures of complexes of Piwi PAZ domains with piRNA, utilizing two major methods in structural biology, NMR spectroscopy, and X-ray crystallography, and derive very similar structures with similar resolution. © 2011 Elsevier Ltd. Source


Yalachkov Y.,Goethe University Frankfurt | Naumer M.J.,Maastricht University
Journal of Neurophysiology | Year: 2011

The study of Wagner et al. (J Neurosci 31: 894-898, 2011) reveals the neural correlates of spontaneously activated action representations in smokers when subjects watch movie characters smoke. We stress the importance of differentiating how these representations are activated: while the anterior intraparietal sulcus and inferior frontal gyrus are part of the mirror neuron system of smokers, the middle frontal gyrus, premotor cortex, and superior parietal lobule represent the smokingrelated tool use skills and action knowledge activated by smoking paraphernalia. © 2011 the American Physiological Society. Source


Krejtschi C.,Goethe University Frankfurt | Hauser K.,University of Konstanz
European Biophysics Journal | Year: 2011

The thermal stability and folding dynamics of polyglutamic acid were studied by equilibrium circular dichroism (CD), Fourier-transform infrared (FTIR), and time-resolved temperature-jump infrared (IR) spectroscopy. Polyglutamic acid (PGA) forms α-helical peptides in aqueous solution and is an ideal model system to study the helix-coil transition. Melting curves were monitored with CD and FTIR as a function of pD. At low pD, PGA aggregates at temperatures above 323 K, whereas at pD >5, unfolding and refolding are reversible. At pD 5.4, a helix-coil transition occurs with a transition temperature T m of 307 K. At slightly higher pD of 6.2, the peptide conformation is already in a coil structure and only small conformational changes occur upon heating. We determined the equilibrium constant for the reversible helix-coil transition at pD 5.4. The dynamics of this transition was measured at single IR wavelengths after a nanosecond laser-excited temperature jump of ΔT ∼ 10 K. Relaxation constants decreased with increasing peptide temperature. Folding and unfolding rates as well as activation energies were extracted based on a two-state model. Our study shows how equilibrium and time-resolved infrared spectroscopic data can be combined to characterize a structural transition and to analyze folding mechanisms. © 2011 European Biophysical Societies' Association. Source


Lucke J.,Goethe University Frankfurt | Eggert J.,Honda Research Institute Europe
Journal of Machine Learning Research | Year: 2010

We show how a preselection of hidden variables can be used to efficiently train generative models with binary hidden variables. The approach is based on Expectation Maximization (EM) and uses an efficiently computable approximation to the sufficient statistics of a given model. The computational cost to compute the sufficient statistics is strongly reduced by selecting, for each data point, the relevant hidden causes. The approximation is applicable to a wide range of generative models and provides an interpretation of the benefits of preselection in terms of a variational EM approximation. To empirically show that the method maximizes the data likelihood, it is applied to different types of generative models including: a version of non-negative matrix factorization (NMF), a model for non-linear component extraction (MCA), and a linear generative model similar to sparse coding. The derived algorithms are applied to both artificial and realistic data, and are compared to other models in the literature. We find that the training scheme can reduce computational costs by orders of magnitude and allows for a reliable extraction of hidden causes. © 2010 Jorg Liicke and Julian Eggert. Source


Stangier U.,Goethe University Frankfurt | Schramm E.,Albert Ludwigs University of Freiburg | Heidenreich T.,Esslingen University of Applied Sciences | Berger M.,Albert Ludwigs University of Freiburg | Clark D.M.,Kings College London
Archives of General Psychiatry | Year: 2011

Context: Cognitive therapy (CT) focuses on the modification of biased information processing and dysfunctional beliefs of social anxiety disorder (SAD). Interpersonal psychotherapy (IPT) aims to change problematic interpersonal behavior patterns thatmay have an important role in the maintenance of SAD. No direct comparisons of the treatments for SAD in an outpatient setting exist. Objective: To compare the efficacy of CT, IPT, and a waiting-list control (WLC) condition. Design: Randomized controlled trial. Setting: Two academic outpatient treatment sites. Patients: Of 254 potential participants screened, 117 had a primary diagnosis of SAD and were eligible for randomization; 106 participants completed the treatment or waiting phase. Interventions: Treatment comprised 16 individual sessions of either CT or IPT and 1 booster session. Twenty weeks after randomization, posttreatment assessment was conducted and participants in the WLC received 1 of the treatments. Main Outcome Measures: The primary outcome was treatment response on the Clinical Global Impression Improvement Scale as assessed by independent masked evaluators. The secondary outcome measures were independent assessor ratings using the Liebowitz Social Anxiety Scale, the Hamilton Rating Scale for Depression, and patient self-ratings of SAD symptoms. Results: At the posttreatment assessment, response rates were 65.8% for CT, 42.1% for IPT, and 7.3% for WLC. Regarding response rates and Liebowitz Social Anxiety Scale scores, CT performed significantly better than did IPT, and both treatments were superior to WLC. At 1-year follow-up, the differences between CT and IPT were largely maintained, with significantly higher response rates in the CT vs the IPT group (68.4% vs 31.6%) and better outcomes on the Liebowitz Social Anxiety Scale. No significant treatment X site interactions were noted. Conclusions: Cognitive therapy and IPT led to considerable improvements that were maintained 1 year after treatment; CT was more efficacious than was IPT in reducing social phobia symptoms. ©2011 American Medical Association. All rights reserved. Source


Coja-Oghlan A.,Goethe University Frankfurt | Vilenchik D.,Weizamnn Institute
Proceedings - Annual IEEE Symposium on Foundations of Computer Science, FOCS | Year: 2013

In this paper we establish a substantially improved lower bound on the k-colorability threshold of the random graph G(n,m) with n vertices and m edges. The new lower bound is ≈ 1.39 less than the 2k ln k-ln k first-moment upper bound (and ≈ 0.39 less than the 2k ln k - ln k - 1 physics conjecture). By comparison, the best previous bounds left a gap of about 2 + lnk, unbounded in terms of the number of colors [Achlioptas, Naor: STOC 2004]. Furthermore, we prove that, in a precise sense, our lower bound marks the so-called condensation phase transition predicted on the basis of physics arguments [Krzkala et al.: PNAS 2007]. Our proof technique is a novel approach to the second moment method, inspired by physics conjectures on the geometry of the set of k-colorings of the random graph. Copyright © 2013 by The Institute of Electrical and Electronics Engineers, Inc. Source


JNJ-26481585 is a second-generation histone deacetylase inhibitor with broad-range efficacy and improved pharmacodynamic properties. In the present study, we investigated the therapeutic potential of JNJ-26481585 and its molecular mechanisms of action in rhabdomyosarcoma (RMS). Here, we report that JNJ- 26481585’s anticancer activity critically depends on an intact mitochondrial pathway of apoptosis. JNJ-26481585 induces apoptosis and also inhibits long-term clonogenic survival of several RMS cell lines at nanomolar concentrations that cause histone acetylation. Importantly, JNJ-26481585 significantly suppresses tumor growth in vivo in two preclinical RMS models, that is, the chorioallantoic membrane model and a xenograft mouse model. Mechanistically, we identify activation of the mitochondrial pathway of apoptosis as a key event that is critically required for JNJ-26481585-mediated cell death. JNJ-26481585 upregulates expression levels of several BH3-only proteins including Bim, Puma and Noxa, which all contribute to JNJ-26481585-mediated apoptosis, as knockdown of Bim, Puma or Noxa significantly inhibits cell death. This shift toward proapoptotic Bcl-2 proteins promotes activation of Bax and Bak as a critical event, as genetic silencing of Bax or Bak protects against JNJ-26481585-induced apoptosis. Intriguingly, rescue experiments reveal that JNJ-26481585 triggers Bax/Bak activation independently of caspase activation and activates caspase-9 as the initiator caspase in the cascade, as Bcl-2 overexpression, but not the broad-range caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (zVAD.fmk) blocks JNJ-26481585-induced Bax/Bak activation and caspase-9 cleavage. In conclusion, JNJ-26481585 exerts potent antitumor activity against RMS in vitro and in vivo by engaging mitochondrial apoptosis before caspase activation and represents a promising therapeutic for further investigation in RMS.Oncogene advance online publication, 30 November 2015; doi:10.1038/onc.2015.440. © 2015 Macmillan Publishers Limited Source


Sedrakian A.,Goethe University Frankfurt
Journal of Physics: Conference Series | Year: 2013

I review three problems in astrophysics of compacts stars: (i) the phase diagram of warm pair-correlated nuclear matter at sub-saturation densities at finite isospin asymmtery; (ii) the Standard Model neutrino emission from superfluid phases in neutron stars within the Landau theory of Fermi (superfluid) liquids; (iii) the beyond Standard Model physics of axionic cooling of compact stars by the Cooper pair-breaking processes. Source


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

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


Groth S.S.,E-House | Muntermann J.,Goethe University Frankfurt
Decision Support Systems | Year: 2011

The management of financial risk is one of the most challenging tasks of financial institutions. In the last two decades, diverse quantitative models and approaches have been developed and refined to address the impact of volatile markets on business. Whereas existing approaches have intensively utilized structured data such as historical price series, little attention has been paid to unstructured (textual) data, which could be a large source of information in this context. Previous empirical research has shown that certain news stories, such as corporate disclosures, can cause abnormal price behavior subsequent to their publication. On the basis of a data set comprising such news stories as well as intraday stock prices, this paper explores the risk implications of information being newly available to market participants. After showing that such events can significantly drive stock price volatilities, this research aims at identifying among the textual data provided those disclosures that have resulted in most supranormal risk exposures. To this end, four different learners - Naïve Bayes, k-Nearest Neighbour, Neural Network, and Support Vector Machine - have been applied in order to detect patterns in the textual data that could explain increased risk exposure. Two evaluations are presented in order to assess the learning capabilities of the approach in the context of risk management. First, "classic" data mining evaluation metrics are applied and, second, a newly developed simulation-based evaluation method is presented. Evaluation results provide strong evidence that unstructured (textual) data represents a valuable source of information also for financial risk management - a domain in which, in the past, little attention has been paid to unstructured data. With regard to classification performance, it is also shown that there exist significant differences between the applied learning techniques. © 2010 Elsevier B.V. All rights reserved. Source


Roos C.,Goethe University Frankfurt
Molecular membrane biology | Year: 2013

Routine strategies for the cell-free production of membrane proteins in the presence of detergent micelles and for their efficient co-translational solubilization have been developed. Alternatively, the expression in the presence of rationally designed lipid bilayers becomes interesting in particular for biochemical studies. The synthesized membrane proteins would be directed into a more native-like environment and cell-free expression of transporters, channels or other membrane proteins in the presence of supplied artificial membranes could allow their subsequent functional analysis without any exposure to detergents. In addition, lipid-dependent effects on activity and stability of membrane proteins could systematically be studied. However, in contrast to the generally efficient detergent solubilization, the successful stabilization of membrane proteins with artificial membranes appears to be more difficult. A number of strategies have therefore been explored in order to optimize the co-translational association of membrane proteins with different forms of supplied lipid bilayers including liposomes, bicelles, microsomes or nanodiscs. In this review, we have compiled the current state-of-the-art of this technology and we summarize parameters which have been indicated as important for the co-translational association of cell-free synthesized membrane proteins with supplied membranes. Source


Janowski S.,Goethe University Frankfurt
Acta Physica Polonica B, Proceedings Supplement | Year: 2013

Using the U(3)R × U(3)L extended Linear Sigma Model with the ordinary (pseudo)scalar and (axial)vector mesons as well as a scalar glueball, we study the vacuum phenomenology of the scalar-isoscalar resonances f0(1370); f0(1500) and f0(1710). We present here a solution, based only on the masses and not yet on decays, in which the resonances f0(1370) and f0(1500) are predominantly nonstrange and strange q̄q states respectively, and the resonance f0(1710) is predominantly a scalar glueball. Source


Rieper F.,Goethe University Frankfurt
Journal of Computational Physics | Year: 2011

We present a low-Mach number fix for Roe's approximate Riemann solver (LMRoe). As the Mach number Ma tends to zero, solutions to the Euler equations converge to solutions of the incompressible equations. Yet, standard upwind schemes do not reproduce this convergence: the artificial viscosity grows like 1/Ma, leading to a loss of accuracy as Ma → 0. With a discrete asymptotic analysis of the Roe scheme we identify the responsible term: the jump in the normal velocity component Δ U of the Riemann problem. The remedy consists of reducing this term by one order of magnitude in terms of the Mach number. This is achieved by simply multiplying Δ U with the local Mach number. With an asymptotic analysis it is shown that all discrepancies between continuous and discrete asymptotics disappear, while, at the same time, checkerboard modes are suppressed. Low Mach number test cases show, first, that the accuracy of LMRoe is independent of the Mach number, second, that the solution converges to the incompressible limit for Ma → 0 on a fixed mesh and, finally, that the new scheme does not produce pressure checkerboard modes. High speed test cases demonstrate the fall back of the new scheme to the classical Roe scheme at moderate and high Mach numbers. © 2011 Elsevier Inc. Source


Schuchmann S.,Goethe University Frankfurt
Journal of Physics G: Nuclear and Particle Physics | Year: 2011

The nuclear modification factors RAA and RCP of Λ and K0 s in Pb-Pb collisions at √sNN = 2.76 TeV measured by ALICE at the LHC are presented. In central collisions, a strong suppression at high pT (pT > 8 GeV/c) with respect to pp collisions is observed. The pT region below is dominated by an enhancement of Λ over the suppressed K0 s. The results are compared to those of charged hadrons and to Λ from lower collision energies. © CERN 2011. Published under licence by IOP Publishing Ltd. Source


Hofmann S.,Helmholtz Center for Heavy Ion Research | Hofmann S.,Goethe University Frankfurt
Radiochimica Acta | Year: 2011

The new elements from Z = 107 to 112 were synthesized in cold fusion reactions based on targets of lead and bismuth. The principle physical concepts are presented which led to the application of this reaction type in search experiments for new elements. Described are the technical developments from early mechanical devices to experiments with recoil separators. An overview is given of present experiments which use cold fusion for systematic studies and synthesis of new isotopes. Perspectives are also presented for the application of cold fusion reactions in synthesis of elements beyond element 113, the so far heaviest element produced in a cold fusion reaction. Further, the transition of hot fusion to cold fusion is pointed out, which occurs in reactions for synthesis of elements near Z = 126 using actinide targets and beams of neutron rich isotopes of elements from iron to germanium. © by Oldenbourg Wissenschaftsverlag, München. Source


Ploch S.,Biodiversity and Climate Research Center | Thines M.,Biodiversity and Climate Research Center | Thines M.,Goethe University Frankfurt
Molecular Ecology | Year: 2011

Mutualistic interactions of plants with true fungi are a well-known and widespread phenomenon, which includes mycorrhiza and non-mycorrhizal endophytes like species of Epichloë. Despite the fact that these organisms intrude into plants, neither strong defence reactions nor the onset of symptoms of disease can be observed in most or even all infested plants, in contrast to endophytic pathogens. Oomycetes are fungal-like organisms belonging to the kingdom Straminipila, which includes diatoms and seaweeds. Although having evolved many convergent traits with true fungi and occupying similar evolutionary niches, widespread oomycete endophytes are not known to date, although more than 500 endophytic pathogens, including species of the obligate biotrophic genus Albugo, have been described. Here, we report that oomycetes of the genus Albugo are widespread in siliques of natural host populations. A total of 759 plants, encompassing four genera with rare reports of white blister incidents and one with common incidents, were collected from 25 sites in Germany. Nested PCR with species-specific primers revealed that 5-27% of the hosts with rare disease incidence carried asymptomatic Albugo in their siliques, although only on a single plant of 583 individuals, an isolated pustule on a single leaf could be observed. Control experiments confirmed that these results were not because of attached spores, but because of endophytic mycelium. Vertical inheritance of oomycete infections has been reported for several plant pathogens, and it seems likely that in nature this way of transmission plays an important role in the persistence of asymptomatic endophytic Albugo species. © 2011 Blackwell Publishing Ltd. Source


Fulda S.,Goethe University Frankfurt
Experimental Cell Research | Year: 2012

Evasion of apoptosis represents a key mechanism leading to treatment resistance of human cancers. Abnormal regulation of chromatin remodeling has been implied in tumorigenesis as well as treatment resistance. Acetylation of histones represents one of the key posttranslational modifications that contribute to the regulation of chromatin remodeling. Histone acetylation is governed by the balance between enzymes that put acetyl groups on histone tails or, alternatively, remove them. Since a disturbed regulation of histone acetylation plays an important role in cancer formation and progression, a variety of histone deacetylase (HDAC) inhibitors have been developed in recent years to target aberrant HDAC activity. HDAC inhibitors also represent a promising strategy to lower the threshold of cancer cells for apoptosis induction. For example, synergistic induction of apoptosis has been documented for the concomitant use of HDAC inhibitors together with the death receptor ligand TRAIL in a panel of human cancers. Understanding the molecular mechanism that mediates this synergistic drug interaction will be critical to further optimize this approach in order to successfully translate it into a clinical setting. © 2012 Elsevier Inc. Source


Schwarz D.,Goethe University Frankfurt
Proteomics | Year: 2010

The high versatility and open nature of cell-free expression systems offers unique options to modify expression environments. In particular for membrane proteins, the choice of co-translational versus post-translational solubilization approaches could significantly modulate expression efficiencies and even sample qualities. The production of a selection of 134 alpha-helical integral membrane proteins of the Escherichia coli inner membrane proteome focussing on larger transporters has therefore been evaluated by a set of individual cell-free expression reactions. The production profiles of the targets in different cell-free expression modes were analyzed independently by three screening strategies. Translational green fluorescent protein fusions were analyzed as monitor for the formation of proteomicelles after cell-free expression of membrane proteins in the presence of detergents. In addition, two different reaction configurations were implemented and performed either by robotic semi-throughput approaches or by individually designed strategies. The expression profiles were specified for the particular cell-free modes and overall, the production of 87% of the target list could be verified and approximately 50% could already be synthesized in preparative scales. The expression of several selected targets was up-scaled to milliliter volumes and milligram amounts of production. As an example, the flavocytochrome YedZ was purified and its sample quality was demonstrated. Source


Gastmeier P.,Charite - Medical University of Berlin | Breier A.-C.,Charite - Medical University of Berlin | Brandt C.,Goethe University Frankfurt
Journal of Hospital Infection | Year: 2012

Background: Many hospitals use ultraclean ventilation (UVC), also known as laminar airflow systems (LAF), in their operating rooms to decrease rates of surgical site infections (SSIs). However, the evidence for these systems is limited and the additional expenses for LAF are substantial. Aim: To determine the effectiveness of LAF to decrease SSI rates following hip and knee prosthesis. Methods: Systematic review of cohort studies investigating the influence of LAF on SSIs following hip and knee prosthesis published during the last 10 years. Findings: Four cohort studies using the endpoint severe SSI following knee prosthesis and four studies following hip prosthesis were included. No individual study showed a significant benefit for LAF following knee prosthesis but one small study showed a significant benefit following hip prosthesis. However, one individual study showed significantly higher severe SSI rates following knee prosthesis and three studies significantly higher SSI rates following hip prosthesis under LAF conditions. The summary odds ratio was 1.36 (95% confidence interval: 1.06-1.74) for knee prosthesis and 1.71 (1.21-2.41) for hip prosthesis. Conclusions: It would be a waste of resources to establish new operating rooms with LAF, and questionable as to whether LAF systems in existing operating rooms should be replaced by conventional ventilation systems. © 2012 The Healthcare Infection Society. Source


Vlachos A.,Goethe University Frankfurt
Annals of Anatomy | Year: 2012

Synaptopodin (SP) is an actin-binding molecule, which is closely linked with the spine apparatus organelle (SA). Recent experimental evidence suggests that SP containing spines differ in their functional and structural properties from neighboring spines, which do not contain SP. These studies revealed for the first time that SP clusters colocalize with a functional internal source of calcium, which affects synaptic plasticity. Strikingly, SP-cluster associated calcium surges were shown to control synaptic strength in two ways: a ryanodine receptor (RyR) dependent potentiation of synaptic strength was reported, as well as inositol-triphosphate-receptor (IP3R) dependent depression. These results suggested that the SA is an important component of the molecular machinery controlling the calcium-dependent accumulation of AMPA-receptors (AMPA-R) at excitatory synapses. They raise the intriguing possibility that SP/SA could play a role in different forms of synaptic plasticity. © 2011 Elsevier GmbH. Source


Rodel C.,Goethe University Frankfurt | Hofheinz R.,University of Heidelberg | Liersch T.,University of Gottingen
Current Opinion in Oncology | Year: 2012

Purpose of review: To discuss the recent developments of multimodal treatment for patients with local advanced rectal cancer, including incorporation of new chemotherapeutic and targeted agents, and the optimal sequence and timing of treatment components. Recent findings: Five randomized trials have been completed to determine whether the addition of oxaliplatin to preoperative, fluorouracil-based chemoradiotherapy (CRT) offers an advantage compared to single-agent fluorouracil CRT. Early results from the ACCORD 12, STAR-01, and NSAPB R-04 trials did not confirm a significant improvement of early efficacy endpoints with the addition of oxaliplatin, whereas the German CAO/ARO/AIO-04 did. Most of the phase II trials incorporating cetuximab into CRT reported disappointingly low rates of pathologic complete response (pCR); the combination of CRT with VEGF inhibition showed encouraging pCR rates; however, it was associated with increased surgical complications. Novel clinical trials address the role of induction chemotherapy, of delayed, minimal or omitted surgery following CRT, or the omission of radiotherapy for selected patients. Summary: At this time, the use of oxaliplatin or targeted agents as component of multimodality treatment for rectal cancer outside of a clinical trial is not recommended. The inclusion of different treatment options, according to tumor stage, location, imaging features, and response, will render the multimodal treatment approach of rectal cancer more risk-adapted. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Gasche J.A.,Baylor Research Institute | Gasche J.A.,Goethe University Frankfurt | Goel A.,Baylor Research Institute
Future Oncology | Year: 2012

Dysregulation of gene expression is a frequent occurrence in oral squamous cell carcinoma (OSCC). However, accumulating evidence suggests that in contrast to genetics, epigenetic modifications consisting of aberrant DNA methylation, histone modifications and altered expression of miRNAs induce OSCC tumorigenesis and perhaps play a more central role in the evolution and progression of this disease. The unifying theme among these three epigenetic mechanisms remains the same, which is aberrant regulation of gene expression. In this article, we provide a comprehensive review of the impact of epigenetics on oral tumorigenesis with a systematic report on aberrant DNA methylation, histone modifications and miRNA regulation in the pathogenesis of OSCC. We provide insights into recent studies on the prospect of biomarkers for early detection and indication of disease recurrence, and novel treatment modalities. © 2012 Future Medicine Ltd. Source


Lalakulich O.,Justus Liebig University | Gallmeister K.,Goethe University Frankfurt | Mosel U.,Justus Liebig University
Physical Review C - Nuclear Physics | Year: 2012

Background: Nuclear effects can have a significant impact on neutrino-nucleus interactions. In particular, data from neutrino experiments with broad energy distributions require complex theoretical models that are able to take all the relevant channels into account as well as incorporate nuclear effects in both initial and final-state interactions. Purpose: We investigate neutrino and antineutrino scattering on iron and carbon in the energy range from 1 to 50 GeV, which is relevant to current and coming experiments (MINOS, NOνA, and Minerνa). Method: The Giessen Boltzmann-Uehling-Uhlenbeck (GiBUU) model, which implements all reaction channels relevant for neutrino energies under consideration, is used for an investigation of neutrino-nucleus reactions. Results: Our calculations are compared with the recent NOMAD and MINOS data for the integrated inclusive cross sections. Predictions are made for the differential cross sections for semi-inclusive final states (pions, kaons, and nucleons) for the MINOS and NOνA fluxes. Conclusions: Nuclear effects in the initial-state interactions may slightly change the inclusive nuclear cross section as compared to the free nucleon ones. Final-state interactions noticeably change the spectra of the outgoing hadrons. In the Minerνa and NOνA experiments these effects should be visible in the kinetic energy distributions of the final pions, kaons, and nucleons. Secondary interactions play an important role for strangeness production. They make it very difficult to extract the neutrino-induced strangeness production cross section in experiments using nuclear targets. © 2012 American Physical Society. Source


Lalakulich O.,Justus Liebig University | Gallmeister K.,Goethe University Frankfurt | Mosel U.,Justus Liebig University
Physical Review C - Nuclear Physics | Year: 2012

Background: The total inclusive cross sections obtained for quasielastic (QE) scattering in the Mini Booster Neutrino Experiment (MiniBooNE) are significantly larger than those calculated by all models based on the impulse approximation and using the world average value for the axial mass of M A≈1GeV. This discrepancy has led to various, quite different explanations in terms of increased axial masses, changes in the functional form of the axial form factor, increased vector strength in nuclei, and initial two-particle interactions. This is disconcerting since the neutrino energy reconstruction depends on the reaction mechanism. Purpose: We investigate whether exclusive observables, such as nucleon knockout, can be used to distinguish between the various proposed reaction mechanisms. We determine the influence of 2p-2h excitations on the neutrino energy reconstruction. Method: We extend the Giessen Boltzmann-Uehling-Uhlenbeck (GiBUU) model by explicitly incorporating initial 2p-2h excitations. Results: We calculate inclusive cross sections and numbers and spectra of knockout nucleons and show their sensitivity to the presence of 2p-2h initial excitations. We also discuss the influence of 2p-2h excitations on the neutrino energy reconstruction. Conclusions: Inclusive double-differential cross sections, depending only on muon variables, are fairly insensitive to the reaction mechanism. 2p-2h excitations lead to an increase in the number n of knockout nucleons for n≥2, while only the n=1 knockout remains a clean signal of true QE scattering. The spectra of knockout nucleons are also changed, but their shape is hardly affected. In the energy reconstruction, 2p-2h interactions as well as Δ excitations lead to a downward shift of the reconstructed energy; this effect of 2p-2h excitations disappears at higher energies because the 2p-2h influence is spread out over a wider energy range. © 2012 American Physical Society. Source


Lalakulich O.,Justus Liebig University | Mosel U.,Justus Liebig University | Gallmeister K.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

Background: Neutrino oscillation probabilities, which are being measured in long-baseline experiments, depend on neutrino energy. The energy in a neutrino beam, however, is broadly smeared so that the neutrino energy in a particular event is not directly known, but must be reconstructed from final state properties. Purpose: To investigate the effects of different reaction mechanisms on the energy-reconstruction method widely used in long-baseline neutrino experiments taking also pion production into account, and to clarify how the oscillation signal depends on the energy reconstruction. Methods: The Giessen Boltzmann-Uehling-Uhlenbeck (GiBUU) transport model is used for a detailed study of neutrino-nucleus events. Results: The difference between the true-QE and QE-like cross sections in the MiniBooNE experiment is investigated in detail. It is shown that fake QE-like events lead to significant distortions in neutrino energy reconstruction. Flux-folded and unfolded cross sections for QE-like scattering are calculated as functions of both true and reconstructed energies. Flux-folded momentum transfer distributions are calculated as functions of both true and reconstructed momentum transfer. Distributions versus reconstructed values are compared with the experimental data. Also presented are the conditional probability densities of finding a true energy for a given reconstructed energy. We show how the energy-reconstruction procedure influences the measurement of oscillation parameters in T2K experiments. Conclusions: For the reconstruction procedure based on quasielastic (QE) kinematics all other reaction channels besides true-QE scattering show a shift of the reconstructed energy towards lower values as compared to the true energy. In the MiniBooNE and T2K experiments this shift is about 100200 MeV and depends on energy. The oscillation signals are similarly affected. These uncertainties may limit the extraction of a CP violating phase from an oscillation result. © 2012 American Physical Society. Source


Rustamov A.,Goethe University Frankfurt | Gorenstein M.I.,NASU Bogolyubov Institute for Theoretical Physics | Gorenstein M.I.,Frankfurt Institute for Advanced Studies
Physical Review C - Nuclear Physics | Year: 2012

Recently the identity method was proposed to calculate second moments of the multiplicity distributions from event-by-event measurements in the presence of the effects of incomplete particle identification. In this paper the method is extended for higher moments. The moments of smeared multiplicity distributions are calculated using single-particle identity variables. The problem of finding the moments of the multiplicity distributions is reduced to solving a system of linear equations. © 2012 American Physical Society. Source


Khatua S.,University of Siegen | Samanta D.,University of Siegen | Bats J.W.,Goethe University Frankfurt | Schmittel M.,University of Siegen
Inorganic Chemistry | Year: 2012

Two new ruthenium complexes [Ru(bipy)2(PDA)]2+ (1) and [Ru(phen)2(PDA)]2+ (2) (PDA = 1,10-phenanthroline-4,7- dicarboxaldehyde) have been synthesized to detect cyanide based on the well-known formation of cyanohydrins. Both 1[PF6]2 and 2[PF6]2 were fully characterized by various spectroscopic techniques and their solid state structures determined by single-crystal X-ray diffraction. Their anion binding properties in pure and aqueous acetonitrile were thoroughly examined using two different channels, i.e., UV-vis absorption and photoluminescence (PL). After addition of only 2 equiv of CN-, the PL intensity of 1[PF6]2 and 2[PF6] 2 was enhanced ∼55-fold within 15 s along with a diagnostic blue shift of the emission by more than 100 nm. PL titrations of 1[PF 6]2 and 2[PF6]2 with CN- in CH3CN furnished the very high overall cyanohydrin formation constants log β[CN - ] = 15.36 ± 0.44 (β[CN - ] = 2.3 × - 1015 M-2) and log β[CN - ] = 16.37 ± 0.53 (β[CN - ] = 2.3 × 1016 M-2), respectively. For both probes, the second constant, K2, is about 57-84 times less than K1, suggesting that the cyanohydrin reaction is stepwise. The stepwise mechanism is further supported by results of a 1H NMR titration of 2[PF 6]2 with CN-. The high selectivity of 2[PF 6]2 for CN- was established by PL in the presence of other competing anions. Furthermore, the color change from orange-red to yellow and the appearance of a orange luminescence, which can be observed by the naked eye, provides a simple real-time method for cyanide detection. Finally, theoretical calculations were carried out to elucidate the details of the electronic structure and transitions involved in the ruthenium probes and their cyanide adducts. © 2012 American Chemical Society. Source


Baer P.C.,Goethe University Frankfurt
Methods in molecular biology (Clifton, N.J.) | Year: 2011

The versatile differentiation potential of adipose-derived stem cells (ASC) into cells of mesodermal, entodermal, and ectodermal origin places these cells at the forefront of cell-based therapies and cell transplantation. Epithelial differentiation of ASC may either be initiated by direct cell-cell or cell-matrix contacts, by chemical factors like retinoic acid, or via secreted cellular factors like cytokines, interleukins, or growth factors included in conditioned media.This protocol describes methods to induce the in vitro differentiation of ASC from human adipose tissue into the epithelial lineage, and describes the methods used to verify this induced differentiation. We present two differentiation protocols based on either retinoic acid or conditioned medium of cultured epithelial cells. Source


Nitsche M.A.,University of Gottingen | Muller-Dahlhaus F.,Goethe University Frankfurt | Paulus W.,University of Gottingen | Ziemann U.,University of Tubingen
Journal of Physiology | Year: 2012

The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society. Source


Janowski S.,Goethe University Frankfurt
Acta Physica Polonica B, Proceedings Supplement | Year: 2012

In the framework of the U(2) R × U(2) L symmetric linear sigma model with (axial)vector mesons generalized by including a dilaton field, we study the phenomenology of the scalar-isoscalar resonances below 2 GeV. It turns out that in our favoured scenario, the resonance f 0(1370) is predominantly a qq state and f 0(1500) is predominantly a glueball state. Additionally, we are able to calculate the value of the gluon condensate, which is in agreement with lattice QCD results. Source


Shen C.,Ohio State University | Heinz U.,Ohio State University | Huovinen P.,Goethe University Frankfurt | Song H.,Lawrence Berkeley National Laboratory
Physical Review C - Nuclear Physics | Year: 2011

A comprehensive viscous hydrodynamic fit of spectra and elliptic flow for charged hadrons and identified pions and protons from Au+Au collisions of all centralities measured at the Relativistic Heavy Ion Collider (RHIC) is performed and used as the basis for predicting the analogous observables for Pb+Pb collisions at the Large Hadron Collider (LHC) at √s=2.76 and 5.5A TeV. Comparison with recent measurements of the elliptic flow of charged hadrons by the ALICE experiment shows that the model slightly overpredicts the data if the same (constant) specific shear viscosity η/s is assumed at both collision energies. In spite of differences in our assumptions for the equation of state, the freeze-out temperature, the chemical composition at freeze-out, and the starting time for the hydrodynamic evolution, our results agree remarkably well with those of Luzum, indicating robustness of the hydrodynamic model extrapolations. Future measurements of the centrality and transverse momentum dependence of spectra and elliptic flow for identified hadrons predicted here will further test the model and shed light on possible variations of the quark-gluon transport coefficients between RHIC and LHC energies. © 2011 American Physical Society. Source


Barbiellini B.,Northeastern University | Nicolini P.,Goethe University Frankfurt
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

A robust thermodynamic argument shows that a small reduction of the effective coupling constant α of QED greatly enhances the low-energy Compton-scattering cross section and that the Thomson scattering length is connected to a fundamental scale λ. A discussion provides a possible quantum interpretation of this enormous sensitivity to changes in the effective coupling constant α. © 2011 American Physical Society. Source


Gerlach R.,Goethe University Frankfurt
Acta neurochirurgica. Supplement | Year: 2011

To describe our experience with the application of an intraoperative ultra low field magnetic resonance imaging system (ioMRI) PoleStar N20, Medtronic Surgical Navigation Technologies, Louisville, USA during resection control of pituitary adenomas. Forty-four patients were operated on a pituitary adenoma (1 microadenoma, 43 macroadenomas; mean size 26.0 ± 9.7 mm). The ioMRI system was used for navigation and resection control after transseptal, transsphenoidal microsurgical tumour removal using standard instruments and standard microscope. If any accessible tumour remnant was suspected surgery was continued for navigation guided re-exploration and if necessary continued resection. The applications of the scanner integrated navigation system, with a 3-planar reconstruction of the coronal scan, enabled the surgeon to safely approach and remove the tumour. The quality of preoperative tumour visualization with the ultra low field ioMRI in patients with macroadenomas is very good and has a good congruency with the preoperative 1.5 T MRI. For microadenomas the preoperative visualization is poor and very difficult to interpret. In seven patients ioMRI resection control showed residual tumours leading to further resection. After final tumour resection the ioMRI scan documented adequate decompression of the optic pathway in all patients. However, the intraoperative image interpretation was equivocal in four patients in whom it was difficult to distinguish between small intrasellar tumour remnants and perioperative changes. The PoleStar N20 is a safe, helpful and feasible tool for navigation guided pituitary tumour approach. Image interpretation is requires some experience, but decompression of the optic system can be reliable shown in cases with pituitary macroadenomas. This system is of limited value for resection control of pituitary microadenomas. Source


Litvinova E.V.,Helmholtz Center for Heavy Ion Research | Litvinova E.V.,Goethe University Frankfurt | Afanasjev A.V.,Mississippi State University
Physical Review C - Nuclear Physics | Year: 2011

The impact of particle-vibration coupling and polarization effects due to deformation and time-odd mean fields on single-particle spectra is studied systematically in doubly magic nuclei from low-mass Ni56 up to superheavy ones. Particle-vibration coupling is treated fully self-consistently within the framework of the relativistic particle-vibration coupling model. Polarization effects due to deformation and time-odd mean field induced by odd particle are computed within covariant density functional theory. It has been found that among these contributions the coupling to vibrations makes a major impact on the single-particle structure. The impact of particle-vibration coupling and polarization effects on calculated single-particle spectra, the size of the shell gaps, the spin-orbit splittings and the energy splittings in pseudospin doublets is discussed in detail; these physical observables are compared with experiment. Particle-vibration coupling has to be taken into account when model calculations are compared with experiment since this coupling is responsible for observed fragmentation of experimental levels; experimental spectroscopic factors are reasonably well described in model calculations. © 2011 American Physical Society. Source


Christen U.,Goethe University Frankfurt
Immunotherapy | Year: 2013

Antibodies play an important role in autoimmune liver diseases, such as autoimmune hepatitis (AIH). On the one hand, they are essential diagnostic markers to identify not only the presentation of AIH, but also the AIH subtype characterized by the presence of particular antibodies to target autoantigens in the liver. On the other hand, such autoantibodies might be directly involved in the etiology and/or pathogenesis of AIH. This review will reflect on the evidence of how specific autoantibodies influence AIH and will further provide insight into the necessities for generating therapeutic antibodies to treat AIH in the future. © 2013 Future Medicine Ltd. Source


Deng W.-T.,Frankfurt Institute for Advanced Studies | Huang X.-G.,Frankfurt Institute for Advanced Studies | Huang X.-G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2012

We compute the electromagnetic fields generated in heavy-ion collisions by using the HIJING model. Although after averaging over many events only the magnetic field perpendicular to the reaction plane is sizable, we find very strong electric and magnetic fields both parallel and perpendicular to the reaction plane on the event-by-event basis. We study the time evolution and the spatial distribution of these fields. In particular, the electromagnetic response of the quark-gluon plasma can give nontrivial evolution of the electromagnetic fields. The implications of the strong electromagnetic fields on the hadronic observables are also discussed. © 2012 American Physical Society. Source


Pal S.,Tata Institute of Fundamental Research | Bleicher M.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2012

Hadron production and their suppression in Pb+Pb collisions at LHC at a center-of-mass energy of √s NN=2.76 TeV are studied within a multiphase transport (AMPT) model whose initial conditions are obtained from the recently updated HIJING 2.0 model. The centrality dependence of charged hadron multiplicity dN ch/dη at midrapidity was found quite sensitive to the largely uncertain gluon shadowing parameter s g that determines the nuclear modification of the gluon distribution. We find final-state parton scatterings reduce considerably hadron yield at midrapidity and enforces a smaller gluon shadowing to be consistent with dN ch/dη data at LHC. With such a constrained parton shadowing, charged hadron and neutral pion production over a wide transverse momenta range are investigated in AMPT. Relative to nucleon-nucleon collisions, the particle yield in central heavy ion collisions is suppressed due to parton energy loss. While the calculated magnitude and pattern of suppression is found consistent with that measured in Au+Au collisions at √s NN=0.2 TeV at RHIC, at the LHC energy the suppression is overpredicted which may imply the medium formed at LHC is less opaque than expected from simple RHIC extrapolations. Reduction of the QCD coupling constant α s by ~30% in the higher temperature plasma formed at LHC as compared to that at RHIC was found to reproduce the measured suppression at LHC. © 2012 Elsevier B.V. Source


Marschalek R.,Goethe University Frankfurt
British Journal of Haematology | Year: 2011

Infant acute leukaemia is characterised by specific genetic rearrangements and a rapid onset of disease shortly after birth. The vast majority of these cases bear rearranged MLL alleles. However, many facets of MLL-rearranged leukaemia are largely unknown. Basically, there exists a fundamental and evolutionary conserved relationship between the family of MLL/Trithorax proteins and the regulation of HOX gene clusters. Therefore, direct MLL fusion proteins are per se able to deregulate HOX genes, except when reciprocal MLL fusion proteins come into play. This reviews discusses (i) the current situation in MLL-rearranged leukaemia, (ii) the molecular and genetic tools to functionally investigate the many different MLL fusions, (iii) the latency of disease development, (iv) a novel cancer mechanism that has been recently uncovered when different MLL fusion protein complexes were characterized, (v) mutated signalling pathways in MLL-rearranged leukaemia and (vi) presents new ideas on how a given MLL fusion protein may modulate existing signalling pathways in leukaemic cells. The hypothesis is posed that the many different fusion partners of MLL are critically distinct entities for which specific inhibitors should be identified in the future. © 2010 Blackwell Publishing Ltd. Source


Huovinen P.,Goethe University Frankfurt | Petreczky P.,Brookhaven National Laboratory
Journal of Physics G: Nuclear and Particle Physics | Year: 2011

We employ the lattice QCD data on Taylor expansion coefficients to extend our previous parametrization of the equation of state to finite baryon density. When we take into account lattice spacing and quark mass dependence of the hadron masses, the Taylor coefficients at low temperature are equal to those of hadron resonance gas. Thus, the equation of state is smoothly connected to the hadron resonance gas equation of state at low temperatures. We also show how the elliptic flow is affected by this equation of state at the maximum SPS energy. © 2011 IOP Publishing Ltd. Source


Resistance to apoptosis is one of the hallmarks of human cancers and contributes to the insensitivity of many cancers to commonly used treatment approaches. Inhibitor of apoptosis (IAP) proteins, a family of anti-apoptotic proteins, have an important role in evasion of apoptosis, as they can both block apoptosis-signaling pathways and promote survival. High expression of IAP proteins is observed in multiple cancers, including hematological malignancies, and has been associated with unfavorable prognosis and poor patients outcome. Therefore, IAP proteins are currently considered as promising molecular targets for therapy. Indeed, drug-discovery approaches over the last decade aiming at neutralizing IAP proteins have resulted in the generation of small-molecule inhibitors or antisense oligonucleotides that demonstrated in vitro and in vivo antitumor activities in preclinical studies. As some of these strategies have already entered the stage of clinical evaluation, for example, in leukemia, an update on this promising molecular-targeted strategy to interfere with apoptotic pathways is of broad interest. © 2012 Macmillan Publishers Limited. Source


Sisourat N.,University of Heidelberg | Kryzhevoi N.V.,University of Heidelberg | Kolorenc P.,Charles University | Scheit S.,University of Tokyo | And 2 more authors.
Nature Physics | Year: 2010

When an atom is electronically excited, it relaxes by emitting a photon or an electron. These carry essential information on the electronic structure of their emitter. However, if an atom is embedded in a chemical environment, another ultrafast non-radiative decay process called interatomic Coulombic decay (ICD) can become operative. As ICD occurs only in the presence of neighbours, it is highly sensitive to that environment. Therefore, it has the potential to become a powerful spectroscopic method to probe the close environment of a system. ICD has been observed experimentally in van der Waals clusters as well as in hydrogen-bonded systems. A key feature of ICD is that the excited atom can transfer its excess energy to its neighbours over large distances. The giant extremely weakly bound helium dimer is a perfect candidate to investigate how far two atoms can exchange energy. We report here that the two helium atoms within the dimer can exchange energy by ICD over distances of more than 45 times their atomic radius. Moreover, we demonstrate that ICD spectroscopy can be used for imaging vibrational wavefunctions of the ionized-excited helium dimer. © 2010 Macmillan Publishers Limited. All rights reserved. Source


Batic D.,University of Los Andes, Colombia | Nicolini P.,Goethe University Frankfurt
Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics | Year: 2010

We study the stability of the noncommutative Schwarzschild black hole interior by analysing the propagation of a massless scalar field between the two horizons. We show that the spacetime fuzziness triggered by the field higher momenta can cure the classical exponential blue-shift divergence, suppressing the emergence of infinite energy density in a region nearby the Cauchy horizon. © 2010 Elsevier B.V. Source


Bauchle B.,Frankfurt Institute for Advanced Studies | Bleicher M.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2010

Direct photon emission in heavy-ion collisions is calculated within a relativistic micro + macro hybrid model and compared to the microscopic transport model, the Ultra-relativistic Quantum Molecular Dynamics model. In the hybrid approach, the high-density part of the evolution is replaced by an ideal three-dimensional hydrodynamic calculation. This allows the effects of viscosity and full local thermalization, in comparison with the transport model of the ideal fluid dynamics, to be examined. The origin of high-p photons as well as the impact of elementary high-√s collisions is studied. The contribution of different production channels and nonthermal radiation to the spectrum of direct photons is further explored. Detailed comparisons to the measurements by the WA98 Collaboration are also undertaken. © 2010 The American Physical Society. Source


Song T.,Goethe University Frankfurt | Ko C.M.,Texas A&M University
Physical Review C - Nuclear Physics | Year: 2015

Using the relativistic Vlasov-Uehling-Uhlenbeck (RVUU) equation based on mean fields from the nonlinear relativistic NLρ and NLρδ models, which have same nuclear equation of state and symmetry energy but different symmetry energy slope parameters, we study the effect of medium modification of the pion-production threshold on the total pion yield and the π-/π+ ratio in Au+Au collisions. We find that the in-medium threshold effect enhances both the total pion yield and the π-/π+ ratio, compared to those without this effect. Furthermore, including the medium modification of the pion-production threshold leads to a larger π-/π+ ratio for the NLρδ model with a larger symmetry energy parameter than the NLρ model with a smaller symmetry energy parameter, opposite to that found without the in-medium threshold effect. To reproduce the total pion yield measured by the FOPI Collaboration, we introduce a density-dependent cross section for Δ baryon production from nucleon-nucleon collisions, which suppresses the total pion yield but hardly changes the π-/π+ ratio. Because of the small difference in the stiffness of their symmetry energies, the π-/π+ ratios obtained from both the NLρ and NLρδ models are consistent with the FOPI data within the experimental errors. © 2015 American Physical Society. Source


Wagele H.,Zoologisches Forschungsmuseum Alexander Koenig | Klussmann-Kolb A.,Goethe University Frankfurt | Verbeek E.,Zoologisches Forschungsmuseum Alexander Koenig | Schrodl M.,SNSB Zoologische Staatssammlung Munich
Organisms Diversity and Evolution | Year: 2014

Opisthobranchia have experienced an unsettled taxonomic history. At the moment their taxonomy is in state of dramatic flux as recent phylogenetic studies have revealed traditional Opisthobranchia to be paraphyletic or even polyphyletic, allocating some traditional opisthobranch taxa to other groups of Heterobranchia, e.g. Pulmonata. Here we review the history of Opisthobranchia and their subgroups, explain their traditionally proposed relationships, and outline the most recent phylogenetic analyses based on various methods (morphology, single gene and multiple gene analyses, as well as genomic data). We also present a phylogenetic hypothesis on Heterobranchia that, according to the latest results, represents a consensus and is the most probable one available to date. The proposed phylogeny supports the Acteonoidea outside of monophyletic Euthyneura, the basal euthyneuran split into Nudipleura (Nudibranchia plus Pleurobranchoidea) and the recently established taxon Tectipleura. The latter divides into the Euopisthobranchia, containing most of the major traditional opisthobranch clades, and the Panpulmonata, with a mix of the former opisthobranch, putative allogastropod and pulmonate taxa. This "new euthyneuran tree" rejects the traditional taxa Opisthobranchia and Pulmonata, and, in particular, has profound implications for preconceived textbook scenarios of opisthobranch and pulmonate evolution, which must now be reconsidered. In the absence of systematic barriers, research communities - which have traditionally investigated marine and non-marine heterobranchs separately - need to interact and finally merge for the sake of science. © 2013 The Author(s). Source


Psoriasis is a multifaceted and-due to its comorbidities-multi-system disease. This is reflected by the wide spectrum of therapeutic options. Recently, efforts have been made to define evidence-based therapeutic standards to provide orientation for dermatologists' treatment decisions. Costly innovative therapeutics as well as increased awareness of long-term safety issues has led to the definition of objective treatment goals. In this regard, patient-reported outcomes are highly relevant. Here, results of recent developments in the field of evidence-based, patient-centered, goal-oriented therapy of psoriasis are summarized. © Springer-Verlag 2012. Source


Background:We investigated the prognostic role of tumour-associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).Methods:The expression of CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n=106 pre-treatment tumour biopsy samples and was correlated with clinicopathological characteristics, including T-stage, N-stage, grading, tumour localisation, age and sex as well as local failure-free survival (LFFS), distant metastases-free survival (DMFS), progression-free (PFS), and overall survival (OS). Finally, TAMs expression and vessel density (CD31) were examined in n=12 available early local recurrence samples and compared with their matched primary tumours . The diagnostic images and radiotherapy plans of these 12 patients were also analysed. All local recurrences occurred in the high radiation dose region (≥70 Gy).Results:With a median follow-up of 40 months, OS at 2 years was 60.5%. High CD163 expression in primary tumours was associated with decreased OS (P=0.010), PFS (P=0.033), LFFS (P=0.036) and DMFS (P=0.038) in multivariate analysis. CD163 demonstrated a strong prognostic value only in human papillomavirus (p16INK4)-negative patients. Early local recurrence specimens demonstrated a significantly increased infiltration of CD11b+ myeloid cells (P=0.0097) but decreased CD31-positive vessel density (P=0.0004) compared with their matched primary samples.Conclusions:Altogether, baseline CD163 expression predicts for an unfavourable clinical outcome in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of TAMs in mediating response to CRT in patients with HNSCC.British Journal of Cancer advance online publication, 5 August 2014; doi:10.1038/bjc.2014.446 www.bjcancer.com. Source


Ouma S.,Goethe University Frankfurt
Geoforum | Year: 2014

This paper provides a critical review of the literature exploring the growing interest of global finance in farmland and agriculture, which has ensued at a global level since the financial and food crises of 2007/08. It finds that many of the existing works have approached this phenomenon through a more or less structuralist political economy framework that operates with a particular notion of 'financialization'. Despite the insights that work rooted in this intellectual tradition has provided at a macro-level, such a reading exposes several lacunae when it comes to the more practical, sociotechnical dimensions of the finance-driven land rush. After elaborating on these 'black boxes', the review sketches a research agenda that seeks to develop an alternative reading of finance's new love affair with 'real things' from below rather than from above. © 2014 Elsevier Ltd. Source


Over the past decade, private food safety and quality standards have become focal points in the supply chain management of large retailers, reshaping governance patterns in global agrifood chains. In this article, I analyze the relationship between private collective standards and the governance of agrifood markets, using the EUREPGAP/GLOBALGAP standard as a vantage point. I discuss the impact of this standard on the organization of supply chains of fresh vegetables in the Kenyan horticulture industry, focusing on the supply chain relationships and practices among exporters and smallholder farmers. In so doing, I seek to highlight the often-contested nature of the implementation of standards in social fields that are marked by different and distributed principles of evaluating quality, production processes, and legitimate actions in the marketplace. I also reconstruct the challenges and opportunities that exporters and farmers are facing with regard to the implementation of and compliance with standards. Finally, I elaborate on the scope for action that producers and policymakers have under these structures to retain sectoral competitiveness in a global economy of qualities. © 2010 Clark University. Source


Rau J.,Goethe University Frankfurt
Physics Letters, Section A: General, Atomic and Solid State Physics | Year: 2010

I show that whenever a system undergoes a reproducible macroscopic process the mutual distinguishability of macrostates, as measured by their relative entropy, diminishes. This extends the second law which regards only ordinary entropies, and hence only the distinguishability between macrostates and one specific reference state (equidistribution). The new result holds regardless of whether the process is linear or nonlinear. Its proof hinges on the monotonicity of quantum relative entropy under arbitrary coarse grainings, even those that cannot be represented by trace-preserving completely positive maps. © 2010 Elsevier B.V. Source


Torrieri G.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2010

We examine the "naturalness" of the scaling of multiplicity and elliptic flow v2 with rapidity in weakly and strongly coupled systems. We argue that multiplicity scaling is relatively straightforward to incorporate in existing ansatz, and that this scaling is insensitive to the transport properties of the system. On the other hand, we argue that the observed scaling of elliptic flow is problematic to describe within a hydrodynamic model (the Knudsen number K1), but arises more naturally within weakly coupled systems (where the Knudsen number ~1). We conclude with an overview of ways proposed to make weakly coupled systems compatible with the absolute value of elliptic flow, and we indicate experimental probes that could clarify these issues. © 2010 The American Physical Society. Source


Dexheimer V.,Kent State University | Negreiros R.,Federal University of Fluminense | Schramm S.,Goethe University Frankfurt
Physical Review C - Nuclear Physics | Year: 2015

We study the effects of strangeness on the quark sector of a hybrid-star equation of state. Since the model we use to describe quarks is the same as the one we use to describe hadrons, we can also study the effects of strangeness on the chiral symmetry restoration and deconfinement phase transitions (first order or crossover). Finally, we analyze the combined effects of hyperons and quarks on global properties of hybrid stars such as mass, radius, and cooling profiles. It is found that a large amount of strangeness in the core is related to the generation of twin-star solutions, which can have the same mass as the lower or zero strangeness counterpart, but with smaller radii. ©2015 American Physical Society. Source


Sabah C.,Goethe University Frankfurt
IEEE Journal on Selected Topics in Quantum Electronics | Year: 2013

In this paper, a new design of multiband metamaterial (MTM) to be employed in novel electromagnetic components and devices is presented both numerically and experimentally. The structure is designed based on the concentric multiple open-ring architecture in which each ring provides a magnetic resonance at different frequencies. The number of resonances depends on the number of the ring resonators composed by the unit cell. The proposed design enables an application as creating multiband left-handed MTMs by combining the proposed structure with a conducting strip. In addition, an HF application is also designed and presented. The investigated structure, supporting multiband operation, is a potential candidate to achieve efficient electrically small microwave/terahertz (THz) structures and can suitably be used for the miniaturization of microwave and THz components. © 1995-2012 IEEE. Source


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

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


Gros C.,Goethe University Frankfurt
Cognitive Computation | Year: 2010

The primary tasks of a cognitive system are to survive and to maximize a life-long utility function, like the number of offsprings. A direct computational maximization of life-long utility is however not possible in complex environments, especially in the context, of real-world time constraints. The central role of emotions is to serve as an intermediate layer in the space of policies available to agents and animals, leading to a large dimensional reduction of complexity. We review our current understanding of the functional role of emotions, stressing the role of the neuromodulators mediating emotions for the diffusive homeostatic control system of the brain. We discuss a recent proposal, that emotional diffusive control is characterized, in contrast to neutral diffusive control, by interaction effects, viz by interferences between emotional arousal and reward signaling. Several proposals for the realization of synthetic emotions are discussed in this context, together with key open issues regarding the interplay between emotional motivational drives and diffusive control. © Springer Science+Business Media, LLC 2010. Source


Samanta S.K.,University of Siegen | Bats J.W.,Goethe University Frankfurt | Schmittel M.,University of Siegen
Chemical Communications | Year: 2014

A five-component supramolecular nanorotor with reversibly acting brakes has been prepared from a four-component nanorotor by adding the photo- and heat-responsive 2,2′-diazastilbene as a signal transducer. The rotational speed was reversibly switched between 86 and 38 kHz. © The Royal Society of Chemistry 2014. Source


Camm A.J.,St Georges, University of London | Capucci A.,Marche Polytechnic University | Hohnloser S.H.,Goethe University Frankfurt | Torp-Pedersen C.,Copenhagen University | And 4 more authors.
Journal of the American College of Cardiology | Year: 2011

Objectives This randomized double-blind study compared the efficacy and safety of intravenous vernakalant and amiodarone for the acute conversion of recent-onset atrial fibrillation (AF). Background Intravenous vernakalant has effectively converted recent-onset AF and was well tolerated in placebo-controlled studies. Methods A total of 254 adult patients with AF (3 to 48 h duration) eligible for cardioversion were enrolled in the study. Patients received either a 10-min infusion of vernakalant (3 mg/kg) followed by a 15-min observation period and a second 10-min infusion (2 mg/kg) if still in AF, plus a sham amiodarone infusion, or a 60-min infusion of amiodarone (5 mg/kg) followed by a maintenance infusion (50 mg) over an additional 60 min, plus a sham vernakalant infusion. Results Conversion from AF to sinus rhythm within the first 90 min (primary end point) was achieved in 60 of 116 (51.7%) vernakalant patients compared with 6 of 116 (5.2%) amiodarone patients (p < 0.0001). Vernakalant resulted in rapid conversion (median time of 11 min in responders) and was associated with a higher rate of symptom relief compared with amiodarone (53.4% of vernakalant patients reported no AF symptoms at 90 min compared with 32.8% of amiodarone patients; p = 0.0012). Serious adverse events or events leading to discontinuation of study drug were uncommon. There were no cases of torsades de pointes, ventricular fibrillation, or polymorphic or sustained ventricular tachycardia. Conclusions Vernakalant demonstrated efficacy superior to amiodarone for acute conversion of recent-onset AF. Both vernakalant and amiodarone were safe and well tolerated in this study. (A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation [AVRO]; NCT00668759) © 2011 American College of Cardiology Foundation. Source


Rieper F.,Goethe University Frankfurt
Journal of Computational Physics | Year: 2010

It is well known that standard upwind schemes for the Euler equations face a number of problems in the low Mach number regime: stiffness, cancellation and accuracy problems. A new aspect of the accuracy problem, presented in this paper, is the dependence on the type of flux solver: while the accuracy of the HLL scheme massively decreases for Ma → 0 on a given triangular mesh, the Roe scheme remains accurate, i.e. flows of arbitrarily small Mach numbers can - at least in principle - be simulated on a fixed triangular mesh. We give an asymptotic analysis of this phenomenon and present a number of numerical results. © 2009 Elsevier Inc. Source


Fleming I.,Goethe University Frankfurt
Cancer and Metastasis Reviews | Year: 2011

Long thought to be biologically important only as xenobiotic metabolizing enzymes, it is now clear that extrahepatic cytochrome P450 epoxygenases can utilize endogenous substrates such as arachidonic acid, linoleic acid, eicosapentaenoic acid, and docosahexaenoic acid to generate bioactive lipid mediators. The epoxides thus generated can acutely affect vascular tone, and stimulate a spectrum of signaling pathways that affect growth-promoting kinase and transcription factor activity in vascular as well as cancer cells. Endogenous epoxide levels are largely controlled by the activity of the soluble epoxide hydrolase, and specific inhibitors of the enzyme as well as knockout mice are helping to determine the roles of these lipids in physiological and pathological angiogenesis. This review summarizes current knowledge on the aspects of the cytochrome P450/soluble epoxide hydrolase pathway related to vascular homeostasis and cancer. © 2011 Springer Science+Business Media, LLC. Source


Scheiter S.,Biodiversitat und Klimaforschungszentrum LOEWE BiK F | Higgins S.I.,Goethe University Frankfurt
Conservation Letters | Year: 2012

The African elephant is the largest extant terrestrial mammal and a reminder of the Pleistocene megafauna. Their survival is, however, dependent on conservation areas. In some conservation areas, rapidly growing elephant populations have led conservation biologists to ask, how many elephants can these areas support? The debate is polarized by arguments for large populations for economic, social, or ethical reasons and arguments for smaller populations that avoid biodiversity loss. We use a novel dynamic modeling approach to assess how climate change-induced vegetation change may influence the capacity of a conservation area to support large herbivores. The model projects that elephant densities and fire have substantial impacts on vegetation under current climatic conditions. Under future conditions, the capacity to support elephants increases due to CO2-induced increases in woody plant productivity. We conclude that sustainable management in conservation areas needs to be conditioned on the effects of climate change on vegetation. © 2012 Wiley Periodicals, Inc. Source


Bernius S.,Goethe University Frankfurt
Online Information Review | Year: 2010

Purpose - This paper aims at analysing the impact of open access (OA) on the creation, retrieval and transfer of scientific knowledge. In doing so, the focus is set on scientific research as one core function of higher education institutions. It also aims to identify potential advantages of OA over traditional subscription-based publishing models from the viewpoint of academic scientists. Design/methodology/approach - The approach of this study can be classified as analytical conceptual research. First the SECI model of organisational knowledge creation is applied to knowledge management in science (with the university as organisation). In a second step the resulting framework is used to describe influences of OA on the management of scientific knowledge. Findings - OA accelerates the creation and widens the dissemination of scientific knowledge. Subject-based repositories are suggested to provide the best conditions for retrieval of scientific knowledge. Furthermore, in terms of economic efficiency, OA has the potential to significantly decrease the costs of scholarly communication. Research limitations/implications - In this paper the focus of investigation is academic research. Thus in order to get the "big picture" the influence of openly accessible information on knowledge management processes in teaching and administration should also be evaluated. The approach used in this paper seems to be suitable for such an analysis. Practical implications - The findings of the paper are of interest for policy makers in higher education institutions - especially when facing decisions regarding the (financial) support of OA initiatives. Originality/value - The paper adds a theoretically sound approach of analysing OA impacts to the existing literature in this field. © Emerald Group Publishing Limited. Source


Chavakis E.,Institute of Cardiovascular Regeneration | Chavakis E.,Goethe University Frankfurt | Dimmeler S.,Institute of Cardiovascular Regeneration
Antioxidants and Redox Signaling | Year: 2011

Progenitor cells mobilized from the bone marrow are recruited to ischemic tissues and increase neovascularization. Cell therapy is a promising new therapeutic option for treating patients with ischemic disorders. The efficiency of cell therapy to augment recovery after ischemia depends on the sufficient recruitment and engraftment of the cells to the target tissue. Homing to sites of active neovascularization is a complex process depending on a timely and spatially orchestrated interplay between chemokines, chemokine receptors, adhesion molecules (selectins and integrins), and intracellular signaling cascades, including also oxidative signaling. This review will focus on the homing mechanisms of progenitor and stem cells to ischemic tissues. Specifically, we discuss the role of chemokines and adhesion molecules such as selectins and integrins and the crosstalk between chemokines and integrins in progenitor cell homing. © 2011 Mary Ann Liebert, Inc. Source


Fleming I.,Goethe University Frankfurt
Current Opinion in Lipidology | Year: 2011

Purpose of Review: This review highlights recent advances in eicosanoid biology, especially linked to the cytochrome P450 (CYP)/soluble epoxide hydrolase (sEH) axis in vascular biology and disease. Recent Findings: Since the first reports that CYP-derived metabolites of arachidonic acid can elicit vascular smooth muscle hyperpolarization and relaxation, it has become clear that fatty acid epoxides and diols are important lipid signaling molecules. Targeting CYP epoxygenases in vivo is difficult as these enzymes are involved in the metabolism of many currently used clinical agents. However, targeting the sEH which metabolizes fatty acid epoxides to their corresponding diols is a highly effective way of manipulating levels of these lipid mediators in vivo. Indeed, sEH mice are protected against the development of some forms of hypertension, and have altered adipocyte metabolism and insulin resistance, phenomena reproduced by selective sEH inhibitors. Summary: Given that elevated epoxide levels have been linked with decreased blood pressure and inflammation in animal models, inhibitors of the sEH are currently being developed for the treatment of human hypertension and inflammation/atherosclerosis. This review focuses on outlining recent insights gained in the beneficial as well as the potentially adverse aspects of interfering with the CYP/sEH axis. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Kober M.,Goethe University Frankfurt
International Journal of Modern Physics A | Year: 2012

In this paper, a generalized quantization principle for the gravitational field in canonical quantum gravity, especially with respect to quantum geometrodynamics is considered. This assumption can be interpreted as a transfer from the generalized uncertainty principle in quantum mechanics, which is postulated as generalization of the Heisenberg algebra to introduce a minimal length, to a corresponding quantization principle concerning the quantities of quantum gravity. According to this presupposition there have to be given generalized representations of the operators referring to the observables in the canonical approach of a quantum description of general relativity. This also leads to generalized constraints for the states and thus to a generalized WheelerDeWitt equation determining a new dynamical behavior. As a special manifestation of this modified canonical theory of quantum gravity, quantum cosmology is explored. The generalized cosmological WheelerDeWitt equation corresponding to the application of the generalized quantization principle to the cosmological degree of freedom is solved by using Sommerfelds polynomial method. © 2012 World Scientific Publishing Company. Source


Sedrakian A.,Goethe University Frankfurt | Sedrakian A.,Yerevan State University
Physical Review C - Nuclear Physics | Year: 2012

Neutrino emission rate from baryonic matter in neutron stars via weak neutral vector interaction is computed up to order O(vF6), where v F is the Fermi velocity in units of speed of light. The vector current polarization tensors are evaluated with full vertices which include resummed series in the particle-hole channel. The neutrino emissivity is enhanced compared to the O(vF4) order up to 10% for values v F≤0.4 characteristic of baryons in compact stars. © 2012 American Physical Society. Source


Batsikadze G.,University of Gottingen | Moliadze V.,University of Gottingen | Moliadze V.,Goethe University Frankfurt | Paulus W.,University of Gottingen | And 2 more authors.
Journal of Physiology | Year: 2013

Transcranial direct current stimulation (tDCS) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm2 has been shown to induce shifts of cortical excitability during and after stimulation. These shifts are polarity-specific with cathodal tDCS resulting in a decrease and anodal stimulation in an increase of cortical excitability. In clinical and cognitive studies, stronger stimulation intensities are used frequently, but their physiological effects on cortical excitability have not yet been explored. Therefore, here we aimed to explore the effects of 2 mA tDCS on cortical excitability. We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects. Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects, respectively. Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials (MEPs) from the right first dorsal interosseous muscle. Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes, and motor thresholds. Intracortical effects of stimulation were obtained by cortical silent period (CSP), short latency intracortical inhibition (SICI) and facilitation (ICF), and I wave facilitation. The above-mentioned protocols were recorded both before and immediately after tDCS in randomized order. Additionally, single-pulse MEPs, motor thresholds, SICI and ICF were recorded every 30 min up to 2 h after stimulation end, evening of the same day, next morning, next noon and next evening. Anodal as well as cathodal tDCS at 2 mA resulted in a significant increase of MEP amplitudes, whereas 1 mA cathodal tDCS decreased corticospinal excitability. A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed. At 1 mA, cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition. No significant changes were observed in the other protocols. Sham tDCS did not induce significant MEP alterations. These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation, but might also shift the direction of excitability alterations. This should be taken into account for applications of the stimulation technique using different intensities and durations in order to achieve stronger or longer lasting after-effects. © 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society. Source


This review article is based on a state-of-the-art lecture given at the 32nd meeting of the German Child Psychiatry Association in March 2011. It summarizes recent findings from epidemiological studies (comorbid disorders, risk factors), early diagnosis, classification, and evidence-based therapeutic interventions (psychopharmacology, early intervention, group-based behavioural interventions). Intensive research over the last years has led to a better understanding of, and improved therapeutic options for, autism spectrum disorders. © 2012 Verlag Hans Huber, Hogrefe AG, Bern. Source


Segal M.,Weizmann Institute of Science | Vlachos A.,Goethe University Frankfurt | Korkotian E.,Weizmann Institute of Science
Neuroscientist | Year: 2010

The spine apparatus (SA) is an essential component of mature dendritic spines of cortical and hippocampal neurons, yet its functions are still enigmatic. Synaptopodin (SP), an actin-binding protein, colocalizes with the SA. Hippocampal neurons in SP-knockout mice lack SA, and they express lower LTP. SP probably plays a role in synaptic plasticity, but only recently it is being linked mechanistically to synaptic functions. These authors and others have studied endogenous and transfected SP in dendritic spines of cultured hippocampal neurons. They found that spines containing SP generate twice as large responses to flash photolysis of caged glutamate than SP-negative ones. An N-methyl-d-aspartate receptorĝ€"mediated chemical LTP caused accumulation of GFP-GluR1 in spine heads of control but not of shRNA transfected, SP-deficient neurons. SP is linked to calcium stores, because their pharmacological blockade eliminated SP-related enhancement of glutamate responses. Furthermore, release of calcium from stores produces an SP-dependent delivery of GluR1 into spines. Thus, SP plays a crucial role in the calcium store-associated ability of neurons to undergo long-term plasticity. © 2010 The Author(s). Source


Dietrich D.D.,Goethe University Frankfurt
Acta Physica Polonica B, Proceedings Supplement | Year: 2013

We elaborate on the correspondence between a non-conformal 4d quantum field theory over the Minkowski space - e.g. quantum chromodynamics or an extension of the standard model that breaks the electroweak symmetry dynamically - and a 5d description over an AdS spacetime. Among other things, we are tracing contributions that break the conformal symmetry in the 4d theory to the warping of the 5d geometry, which resembles the soft-wall model. Source


Kovacs A.,Goethe University Frankfurt
Algorithmica (New York) | Year: 2010

We provide new bounds for the worst case approximation ratio of the classic Longest Processing Time (Lpt) heuristic for related machine scheduling (Q||C max). For different machine speeds, Lpt was first considered by Gonzalez et al. (SIAM J. Comput. 6(1):155-166, 1977). The best previously known bounds originate from more than 20 years back: Dobson (SIAM J. Comput. 13(4):705-716, 1984), and independently Friesen (SIAM J. Comput. 16(3):554-560, 1987) showed that the worst case ratio of Lpt is in the interval (1.512,1.583), and in (1.52,1.67), respectively. We tighten the upper bound to 1+√3/3≈1.5773, and the lower bound to 1.54. Although this improvement might seem minor, we consider the structure of potential lower bound instances more systematically than former works. We present a scheme for a job-exchanging process, which, repeated any number of times, gradually increases the lower bound. For the new upper bound, this systematic method together with a new idea of introducing fractional jobs, facilitated a proof that is surprisingly simple, relative to the result. We present the upper-bound proof in parameterized terms, which leaves room for further improvements. © 2008 Springer Science+Business Media, LLC. Source


The aim of this study was to develop a child-specific classification system for long bone fractures and to examine its reliability and validity on the basis of a prospective multicentre study. Using the sequentially developed classification system, three samples of between 30 and 185 paediatric limb fractures from a pool of 2308 fractures documented in two multicenter studies were analysed in a blinded fashion by eight orthopaedic surgeons, on a total of 5 occasions. Intra- and interobserver reliability and accuracy were calculated. The reliability improved with successive simplification of the classification. The final version resulted in an overall interobserver agreement of κ = 0.71 with no significant difference between experienced and less experienced raters. In conclusion, the evaluation of the newly proposed classification system resulted in a reliable and routinely applicable system, for which training in its proper use may further improve the reliability. It can be recommended as a useful tool for clinical practice and offers the option for developing treatment recommendations and outcome predictions in the future. Source


Fulda S.,Goethe University Frankfurt | Fulda S.,German Cancer Research Center
Seminars in Cell and Developmental Biology | Year: 2015

Apoptosis is a form of programmed cell death that plays a critical role in the regulation of various physiological and pathophysiological processes. Since apoptosis is typically disturbed in human cancers, therapeutic targeting of apoptosis represents a promising avenue for the development of novel therapeutic approaches. This strategy is particularly relevant, since many currently used anticancer therapies utilize apoptosis signaling pathways to exert their antitumor activities. A better understanding of these signaling networks and their deregulation in human cancers is anticipated to open new perspectives for the development of apoptosis-targeted therapies for the treatment of cancer. © 2015 Elsevier Ltd. Source


Voelcker G.,Goethe University Frankfurt
Journal of Cancer Research and Clinical Oncology | Year: 2016

Purpose: SUM-IAP has been developed with the aim to optimize therapeutic response and minimize toxic reactions of oxazaphosphorine cytostatics. In therapy tests in mice, the primary tumor was successfully eradicated, but animals died due to formation of lethal metastases. We supposed that high activities of SUM-IAP detoxifying enzymes caused metastasis formation in the liver. Therefore, therapy tests with SUM-IAP in combination with cisplatin and N-methylformamide (NMF), which were not detoxified in the liver, were carried out. Method: Antitumor activity was assayed in female CD2F1 mice with advanced subcutaneously growing P388 mice leukemia cells. Result: The results of the therapy tests with SUM-IAP plus cisplatin were as expected: No formation of metastases and long-time survival of more than 100 days were observed; however, the toxicity was increased as measured by decrease in body weight and the number in leukocytes. The results of the tests in combination with NMF were surprising: Applying only half the dose of SUM-IAP used in the experiments with cisplatin, no metastases were found and long-time survivors did not show signs of additional toxicity. Conclusion: NMF strongly enhances the antitumor activity of the oxazaphosphorine cytostatic SUM-IAP in mice with subcutaneously growing P388 mice leukemia cells by an unknown mechanism of action. © 2016 Springer-Verlag Berlin Heidelberg Source


Ochsendorf F.,Goethe University Frankfurt
JDDG - Journal of the German Society of Dermatology | Year: 2010

Background: Inflammatory, medium to severe acne vulgaris is treated with sys - temic antibiotics worldwide. The rationale is an effect on Propionibacterium acnes as well as the intrinsic anti-inflammatory properties of these antibiotics. Al - though there are no correlations between the number of P. acnes and the severity of the disease, associations between the degree of humoral and cellular immune-responses against P. acnes and the severity of acne have been reported. Exact data with respect to daily use of these compounds, such as differential effectiveness or side effects are unavailable. A summary of currently available studies is presented. Methods: The data of studies of systemic antibiotic therapy of acne vulgaris up to 1975, the summary of literature in English up to 1999, a systematic review of minocycline of the year 2002 as well as the data of randomized controlled studies published and listed in Medline thereafter were reviewed. Results: Systemic tetracyclines [tetracycline 1 000 mg/d, doxycycline 100 (-200) mg/d, minocycline 100 (-200) mg/d, lymecycline 300 (-600) mg] and erythromycin 1 000 mg/d are significantly more effective than placebo in the systemic treatment of inflammatory acne. The data for tetracycline are best grounded. Similarly effective is clindamycin. Cotrimoxazole and trimethoprim are likely to be effective. Definite differences between the tetracyclines or between tetracycline and erythromycin cannot be ascertained. The data for the combination with topical treatments (topical benzoyl peroxide (BPO) or retinoids) suggest synergistic effects. Therefore systemic antibiotics should not be used as monotherapy. In case of similar efficacy, other criteria, such as pharmacokinetics (doxycycline, minocycline, lymecycline have longer half-life times than tetracyclines), the rate of side-effects (tetracycline: side effect-rate ∼4 % mild side effects; erythromycin often gastrointestinal complaints; minocycline: rare, but potentially severe hypersensitivity reactions; doxycycline dose-dependent phototoxic reactions), the resistance-rate [percentage of resistant bacteria higher with erythromycin (∼50 %) than with tetracycline-therapy'(∼20 %)], and the costs of therapy have to be taken into account. Conclusions: The systemic antibiotic therapy of widespread papulo-pustular acne not amenable to a topical therapy is effective and well-tolerated. In general therapy can be given for 3 months and should be combined with BPO to prevent resistance. © Blackwell Verlag GmbH. Source


Freydenberger D.D.,Goethe University Frankfurt | Reidenbach D.,Loughborough University
Information and Computation | Year: 2010

We study the inclusion problem for pattern languages, which-due to Jiang et al. [T. Jiang, A. Salomaa, K. Salomaa, S. Yu, Decision problems for patterns, Journal of Computer and System Sciences 50 (1995) 53-63]-is known to be undecidable. More precisely, Jiang et al. demonstrate that there is no effective procedure deciding the inclusion for the class of all pattern languages over all alphabets. Most applications of pattern languages, however, consider classes over fixed alphabets, and therefore it is practically more relevant to ask for the existence of alphabet-specific decision procedures. Our first main result states that, for all but very particular cases, this version of the inclusion problem is also undecidable. The second main part of our paper disproves the prevalent conjecture on the inclusion of so-called similar E-pattern languages, and it explains the devastating consequences of this result for the intensive previous research on the most prominent open decision problem for pattern languages, namely the equivalence problem for general E-pattern languages. © 2009 Elsevier Inc. All rights reserved. Source


Hohnloser S.H.,Goethe University Frankfurt
Clinical Cardiology | Year: 2012

Over the last decade, several rhythm-versus rate-control trails in patients with atrial fibrillation (AF) have failed to demonstrate benefit of the rhythm control strategy with respect to mortality and morbidity. This had let to the guideline recommendation that antiarrhythmic drug therapy should be considered predominantly for sympt0matic improvement of patients. Recent trails and meta-analyses have demonstrated that amiodarone is the most antiarrhythmic drug currently available. However, its use has been associated with many adverse effects. Currently, dronedarone is the only available antiarrhythmic drug which has shown a reduction in cardiovascular hospitalizations in medium-risk AF patients. However, the drug was associated with increased mortality in patients with recently decompensated heart failure. Hence, antiarrhythmic drug therapy has to be evaluated in patients with AF on an individual patients basis. © 2012 Wiley Periodicals, Inc. Source


Avigad D.,Hebrew University of Jerusalem | Gerdes A.,Goethe University Frankfurt | Morag N.,Hebrew University of Jerusalem | Bechstadt T.,Jagiellonian University
Gondwana Research | Year: 2012

U-Pb-Hf of detrital zircons from diverse Cambrian units in Morocco and Sardinia were investigated in order to clarify the sandstone provenance and how it evolved with time, to assess whether the detrital spectra mirror basement crustal composition and whether they are a reliable pointer on the ancestry of peri-Gondwanan terranes. Coupled with Hf isotopes, the detrital age spectra allow a unique perspective on crustal growth and recycling in North Africa, much of which is concealed below Phanerozoic sediments.In Morocco, the detrital signal of Lower Cambrian arkose records local crustal evolution dominated by Ediacaran (0.54-0.63Ga) and Late-Paleoproterozoic (1.9-2.2Ga; Eburnian) igneous activity. A preponderance of the Neoproterozoic detrital zircons possess positive ε Hf(t) values and their respective Hf model ages (T DM) concentrate at 1.15Ga. In contrast, rather than by Ediacaran, the Neoproterozoic detrital signal from the Moroccan Middle Cambrian quartz-rich sandstone is dominated by Cryogenian-aged detrital zircons peaking at 0.65Ga alongside a noteworthy early Tonian (0.95Ga) peak; a few Stenian-age (1.0-1.1Ga) detrital zircons are also distinguished. The majority of the Neoproterozoic zircons displays negative ε Hf(t), indicating the provenance migrated onto distal Pan-African terranes dominated by crustal reworking. Terranes such as the Tuareg Shield were a likely provenance. The detrital signal of quartz-arenites from the Lower and Middle Cambrian of SW Sardinia resembles the Moroccan Middle Cambrian, but 1.0-1.1Ga as well as ~2.5Ga detrital zircons are more common. Therefore, Cambrian Sardinia may have been fed from different sources possibly located farther to the east along the north Gondwana margin. 1.0-1.1Ga detrital zircons abundant in Sardinia generally display negative ε Hf(t) values while 0.99-0.95Ga detrital zircons (abundant in Morocco) possess positive ε Hf(t), attesting for two petrologically-different Grenvillian sources. A paucity of detrital zircons younger than 0.6Ga is a remarkable feature of the detrital spectra of the Moroccan and Sardinian quartz-rich sandstones. It indicates that late Cadomian orogens fringing the northern margin of North Africa were low-lying by the time the Cambrian platform was deposited. About a quarter of the Neoproterozoic-aged detrital zircons in the quartz-rich sandstones of Morocco (and a double proportion in Sardinia) display positive ε Hf(t) values indicating considerable juvenile crust addition in North Africa, likely via island arc magmatism. A substantial fraction of the remaining Neoproterozoic zircons which possess negative ε Hf(t) values bears evidence for mixing of old crust with juvenile magmas, implying crustal growth in an Andean-type setting was also significant in this region. © 2011 International Association for Gondwana Research. Source


Weberschock T.,Goethe University Frankfurt
Cochrane database of systematic reviews (Online) | Year: 2012

Mycosis fungoides is the most common type of cutaneous T-cell lymphoma, a malignant, chronic disease initially affecting the skin. Several therapies are available, which may induce clinical remission for a time. To assess the effects of interventions for mycosis fungoides in all stages of the disease. We searched the following databases up to January 2011: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2010), and LILACS (from 1982). We also checked reference lists of included studies for further references to relevant RCTs. We searched online trials registries for further references to unpublished trials and undertook a separate search for adverse effects of interventions for mycosis fungoides in non-RCTs in MEDLINE in May 2011. Randomised controlled trials (RCTs) of interventions for mycosis fungoides in people with any stage of the disease. At least 90% of participants in the trials must have been diagnosed with mycosis fungoides (Alibert-Bazin-type). Two authors independently assessed eligibility and methodological quality for each study and carried out data extraction. We resolved any disagreement by discussion. Primary outcomes were the impact on quality of life and the safety of interventions. When available, we reported on our secondary outcomes, which were the improvement or clearance of skin lesions, disease-free intervals, survival rates, relapse rates, and rare adverse effects. When possible, we combined homogeneous studies for meta-analysis. We used The Cochrane Collaboration's 'Risk of bias' tool to assess the internal validity of all included studies in six different domains. The review included 14 RCTs involving 675 participants, covering a wide range of interventions. Eleven of the included trials assessed participants in clinical stages IA to IIB only (please see Table 1 for definitions of these stages).Internal validity was considerably low in studies with a high or unclear risk of bias. The main reasons for this were low methodological quality or missing data, even after we contacted the study authors, and a mean dropout rate of 26% (0% to 72%). Study size was generally small with a minimum of 4 and a maximum of 103 participants. Only one study provided a long enough follow-up for reliable survival analysis.Included studies assessed topical treatments, such as imiquimod, peldesine, hypericin, nitrogen mustard, as well as intralesional injections of interferon-α (IFN-α). The light therapies investigated included psoralen plus ultraviolet A light (PUVA), extracorporeal photopheresis (photochemotherapy), and visible light. Oral treatments included acitretin, bexarotene, and methotrexate. Treatment with parenteral systemic agents consisted of denileukin diftitox; a combination of chemotherapy and electron beam radiation; and intramuscular injections of active transfer factor. Nine studies evaluated therapies by using an active comparator; five were placebo-controlled RCTs.Twelve studies reported on common adverse effects, while only two assessed quality of life. None of these studies compared the health-related quality of life of participants undergoing different treatments. Most of the reported adverse effects were attributed to the interventions. Systemic treatments, and here in particular a combined therapeutic regimen of chemotherapy and electron beam, bexarotene, or denileukin diftitox, showed more adverse effects than topical or skin-directed treatments.In the included studies, clearance rates ranged from 0% to 83%, and improvement ranged from 0% to 88%. The meta-analysis combining the results of 2 trials comparing the effect of IFN-α and PUVA versus PUVA alone showed no significant difference in the relative risk of clearance: 1.07 (95% confidence interval 0.87 to 1.31). None of the included studies demonstrated a significant increase in disease-free intervals, relapse, or overall survival. This review identified trial evidence for a range of different topical and systemic interventions for mycosis fungoides. Because of substantial heterogeneity in design, small sample sizes, and low methodological quality, the comparative safety and efficacy of these interventions cannot be established on the basis of the included RCTs. Taking into account the possible serious adverse effects and the limited availability of efficacy data, topical and skin-directed treatments are recommended first, especially in the early stages of disease. More aggressive therapeutic regimens may show improvement or clearance of lesions, but they also result in more adverse effects; therefore, they are to be considered with caution. Larger studies with comparable, clearly-defined end points for all stages of mycosis fungoides, and a focus on safety, quality of life, and duration of remission as part of the outcome measures, are necessary. Source


Muller-Dahlhaus F.,University of Tubingen | Vlachos A.,Goethe University Frankfurt
Frontiers in Molecular Neuroscience | Year: 2013

Despite numerous clinical studies, which have investigated the therapeutic potential of repetitive transcranial magnetic stimulation (rTMS) in various brain diseases, our knowledge of the cellular and molecular mechanisms underlying rTMS-based therapies remains limited. Thus, a deeper understanding of rTMS-induced neural plasticity is required to optimize current treatment protocols. Studies in small animals or appropriate in vitro preparations (including models of brain diseases) provide highly useful experimental approaches in this context. State-of-the-art electrophysiological and live-cell imaging techniques that are well established in basic neuroscience can help answering some of the major questions in the field, such as (i) which neural structures are activated during TMS, (ii) how does rTMS induce Hebbian plasticity, and (iii) are other forms of plasticity (e.g., metaplasticity, structural plasticity) induced by rTMS? We argue that data gained from these studies will support the development of more effective and specific applications of rTMS in clinical practice. © 2013 Müller-DahlhausandVlachos. Source


Dotsch V.,Goethe University Frankfurt
Cold Spring Harbor perspectives in biology | Year: 2010

p73 and p63 are two homologs of the tumor suppressive transcription factor p53. Given the high degree of structural similarity shared by the p53 family members, p73 and p63 can bind and activate transcription from the majority of the p53-responsive promoters. Besides overlapping functions shared with p53 (i.e., induction of apoptosis in response to cellular stress), the existence of extensive structural variability within the family determines unique roles for p63 and p73. Their crucial and specific functions in controlling development and differentiation are well exemplified by the p63 and p73 knockout mouse phenotypes. Here, we describe the contribution of p63 and p73 to human pathology with emphasis on their roles in tumorigenesis and development. Source


Uhlhaas P.J.,University of Glasgow | Singer W.,Max Planck Institute for Brain Research | Singer W.,Ernst Strungmann Institute (ESI) for Neuroscience | Singer W.,Goethe University Frankfurt
Biological Psychiatry | Year: 2015

A considerable body of work over the last 10 years combining noninvasive electrophysiology (electroencephalography/magnetoencephalography) in patient populations with preclinical research has contributed to the conceptualization of schizophrenia as a disorder associated with aberrant neural dynamics and disturbances in excitation/inhibition balance. This complements previous research that has largely focused on the identification of abnormalities in circumscribed brain regions and on disturbances of dopaminergic mechanisms as a cause of positive symptoms and executive deficits. In the current review, we provide an update on studies focusing on aberrant neural dynamics. First, we discuss the role of rhythmic activity in neural dynamics and in the coordination of distributed neuronal activity into organized neural states. This is followed by an overview on the current evidence for impaired neural oscillations and synchrony in schizophrenia and associated abnormalities in gamma-aminobutyric acidergic and glutamatergic neurotransmission. Finally, we discuss the distinction between fundamental symptoms, which are reflected in cognitive deficits, and psychotic, accessory symptoms, the latter likely constituting a compensatory response for aberrant neuronal dynamics. © 2015 Society of Biological Psychiatry. Source


The positioning of a patient in a "prone position" ("face down position", fdp) after pars plana vitrectomy with gas tamponade has been discussed controversially since the beginning of macular surgery. The "prone positioning" is almost standard although the duration varies. In most of the study designs for macular surgery "face-down positioning" is advised. However it is not clearly described how the "prone position" was achieved. In most of the studies it is not shown if the patients had suitable aids and how long and how efficiently they used them. Experience while practising this shows that the patient's compliance is a great challenge. Patients are mostly unable to comply, which could result in refusal. In our prospective, controlled and randomised pilot study we observed postoperatively 40 patients who all underwent a pars-plana vitrectomy and sulfur hexafluoride-gastamponade (SF6 25%). All patients of the supported group (SG) and the control group (CG) were requested to keep their face downwards until the gas bubble was resorbed completely. In the postoperative time in hospital the participants of the SG used a simple prone-positioning support. In the time at home after hospital, the patients were supplied with an inflatable device. In this trial we wanted to show whether or not it is possible to improve the patient's compliance by using a prone-positioning support, designed to be particularly comfortable, so that real time in "face-down position" in hours per day could be increased significantly. Additionally, the contentment of the patient in reference to the available supports and the appearance of complications has been reported. In particular the real time of "fdp" in hours per day (24 h) varied greatly (SG: 19.5/24; CG: 5.5/24; P < 0.0001). Equivalent results were reflected in the contentment in reference to the available supports (SG: 99%; CG: 25%; P < 0.0001). Postoperative complications such as moderate or severe back-, neck- or headache only were observed in the CG. Development of a postoperative cataract was observed mainly in the non-supported group. By placing supports at the disposal of the patients, it is possible to improve significantly the compliance after surgery. To succeed in using the prone position also at home it is necessary to supply the patient with a support which is comfortable, cheap and easy to handle. © Georg Thieme Verlag KG Stuttgart · New York. Source


He L.,Goethe University Frankfurt | Huang X.-G.,Indiana University Bloomington
Annals of Physics | Year: 2013

We present a theoretical study of the superfluidity and the corresponding collective modes in two-component atomic Fermi gases with s-wave attraction and synthetic Rashba spin-orbit coupling. The general effective action for the collective modes is derived from the functional path integral formalism. By tuning the spin-orbit coupling from weak to strong, the system undergoes a crossover from an ordinary BCS/BEC superfluid to a Bose-Einstein condensate of rashbons. We show that the properties of the superfluid density and the Anderson-Bogoliubov mode manifest this crossover. At large spin-orbit coupling, the superfluid density and the sound velocity become independent of the strength of the s-wave attraction. The two-body interaction among the rashbons is also determined. When a Zeeman field is turned on, the system undergoes quantum phase transitions to some exotic superfluid phases which are topologically nontrivial. For the two-dimensional system, the nonanalyticities of the thermodynamic functions and the sound velocity across the phase transition are related to the bulk gapless fermionic excitation which causes infrared singularities. The superfluid density and the sound velocity behave nonmonotonically: they are suppressed by the Zeeman field in the normal superfluid phase, but get enhanced in the topological superfluid phase. The three-dimensional system is also studied. © 2013 Elsevier Inc. Source


Romanos G.E.,Goethe University Frankfurt
The International journal of oral & maxillofacial implants | Year: 2012

Extractions in partially edentulous patients often lead to insufficient stability of an existing partial prosthesis and a need for additional anchorage. Implants may therefore be placed as supplementary abutments to increase patient comfort and satisfaction. The aim of this study was to evaluate the long-term clinical outcome of implants combined with teeth to support telescopic abutment-retained removable full-arch prostheses under an immediate functional loading protocol. The present retrospective study included implants placed and connected via removable prostheses with periodontally healthy teeth immediately postplacement using prefabricated abutments. Secondary copings, precisely fit to the abutments, were placed and the partial dentures were relined chairside. The prosthetic restorations were not removed for 10 days. Clinical and radiographic evaluations of implants loaded for at least 2 years were performed. One hundred ten implants with a progressive thread design (Ankylos, Dentsply) were placed in 55 patients (mean age, 63.51±9.95 years). Twenty-five implants were placed in fresh extraction sockets (22.73%) and 85 implants were placed in healed ridges. All implants were placed 2 to 3 mm subcrestally (measured from the midfacial bone level). After a mean follow-up of 61.58±28.47 months (range, 24 to 125 months), there were only three failures (2.73%); another six implants (5.45%) displayed crestal bone loss greater than 2 mm but remained stable. Therefore, the failure rate was 8.18% for the entire observation period of 5.13 years. The success rate was 91.82% and the cumulative survival rate was 97.27%. All patients were satisfied with the stability of their prostheses, and no prosthetic, peri-implant, or abutment tooth problems were observed. Telescopic tooth-implant-supported mandibular restorations with immediate loading present an alternative prosthetic solution for partially edentulous patients, providing a long-term predictable clinical outcome. Source


Autism Spectrum Disorder (ASD) in DSM-5 comprises the former DSM-IV-TR diagnoses of Autistic Disorder, Asperger's Disorder and PDD-nos. The criteria for ASD in DSM-5 were considerably revised from those of ICD-10 and DSM-IV-TR. The present article compares the diagnostic criteria, presents studies on the validity and reliability of ASD, and discusses open questions. It ends with a clinical and research perspective. © 2014 Huber, Hogrefe AG. Source


Uhlhaas P.J.,Max Planck Institute for Brain Research | Singer W.,Max Planck Institute for Brain Research | Singer W.,Goethe University Frankfurt | Singer W.,Ernst Strungmann Institute (ESI) for Neuroscience
Schizophrenia Bulletin | Year: 2011

Recent data from developmental cognitive neuroscience highlight the profound changes in the organization and function of cortical networks during the transition from adolescence to adulthood. While previous studies have focused on the development of gray and white matter, recent evidence suggests that brain maturation during adolescence extends to fundamental changes in the properties of cortical circuits that in turn promote the precise temporal coding of neural activity. In the current article, we will highlight modifications in the amplitude and synchrony of neural oscillations during adolescence that may be crucial for the emergence of cognitive deficits and psychotic symptoms in schizophrenia. Specifically, we will suggest that schizophrenia is associated with impaired parameters of synchronous oscillations that undergo changes during late brain maturation, suggesting an important role of adolescent brain development for the understanding, treatment, and prevention of the disorder. © The Author 2009. Source


Bernd A.,Goethe University Frankfurt
Phytochemistry Reviews | Year: 2014

Curcumin, a dietary pigment from the plant Curcuma longa, inhibits cell proliferation and induces apoptosis in different cell lines. The therapeutic benefit is hampered by a very low absorption after trans-dermal or oral application. Therefore, great efforts were undertaken to enhance the effectiveness of curcumin. Recently, it was demonstrated that curcumin offers the described effects also at low concentrations (0.2-1 μg/ml) when applied in combination with UVA or visible light. The efficacy of this combination was shown in human epidermal keratinocytes and in a panel of other cell species in vitro as well as in a xenograft tumor model with A431 tumor cells injected subcutaneously in the flanks of NMRI nude mice in vivo. The treatment of keratinocytes with curcumin and light resulted in the inhibition of cell growth, and in the induction of apoptosis, whereas no toxic cell membrane damage was detectable. The treatment of tumor bearing nude mice with curcumin and visible light resulted in reduced tumor volumes, reduced proliferation rates, and the induction of apoptosis in the tumors. On the molecular level inhibition of extracellular regulated kinases 1/2 and epidermal growth factor receptor was observed which may aid to inhibition of proliferation and induction of apoptosis. This review covers the experiences of the new combination treatment of human tumors. © 2013 The Author(s). Source


Risk reasoning has become the common-sense mode of knowledge production in the health sciences. Risk assessment techniques of modern epidemiology also co-shape the ways genomic data are translated into population health. Risk computations (e.g., in preventive medicine, clinical decision-support software, or web-based self-tests), loop results from epidemiological studies back into everyday life. Drawing from observations at various European research sites, I analyze how epidemiological techniques mediate and enact the linkages between genomics and public health. This article examines the epidemiological apparatus as a generative machine that is socially performative. The study design and its reshuffling of data and categories in risk modeling recombine old and new categories from census to genomics and realign genes/environment and nature/culture in novel and hybrid ways. In the Euro-American assemblage of risk reasoning and related profiling techniques, the individual and the population are no longer separate but intimately entangled. © 2013 by the American Anthropological Association. Source


Neill T.,Thomas Jefferson University | Schaefer L.,Goethe University Frankfurt | Iozzo R.V.,Thomas Jefferson University
American Journal of Pathology | Year: 2014

Autophagy plays an essential role in maintaining an intricate balance between nutrient demands and energetic requirements during normal homeostasis. Autophagy recycles metabolic substrates from nonspecific bulk degradation of proteins and excess or damaged organelles. Recent work posits an active and dynamic signaling role for extracellular matrix-evoked autophagic regulation, that is, allosteric and independent of prevailing nutrient conditions. Several candidates, representing a diverse repertoire of matrix constituents (decorin, collagen VI, laminin α2, endostatin, endorepellin, and kringle V), can modulate autophagic signaling pathways. Importantly, a novel principle indicates that matrix constituents can differentially modulate autophagic induction and repression via interaction with specific receptors. Most of the matrix-derived factors described here appear to control autophagy in a canonical manner but independent of nutrient deprivation. Because the molecular composition and structure of the extracellular matrix are dynamically remodeled during various physiological and pathological conditions, we propose that matrix-regulated autophagy is key for maintaining proper tissue homeostasis and disease prevention, such as cancer progression and muscular dystrophies. © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. Source


Fischer C.S.,Justus Liebig University | Luecker J.,University of Heidelberg | Luecker J.,Goethe University Frankfurt | Welzbacher C.A.,Justus Liebig University
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

We investigate the phase structure of QCD at finite temperature and light-quark chemical potential. We improve upon earlier results for Nf=2+1 dynamical quark flavors and investigate the effects of charm quarks in an extension to Nf=2+1+1. We determine the quark condensate and the Polyakov loop potential using solutions of a coupled set of (truncated) Dyson-Schwinger equations for the quark and gluon propagators of Landau gauge QCD. At zero chemical potential we find excellent agreement with results from lattice-QCD. With input fixed from physical observables we find only a very small influence of the charm quark on the resulting phase diagram at finite chemical potential. We discuss the location of the emerging critical end point and compare with expectations from lattice gauge theory. © 2014 American Physical Society. Source


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

The decay of the vacuum due to the presence of an electric field is expected to be delayed by a confining force. We demonstrate that this feature is captured by our model for hadrons based on the worldline formalism. Our model, while based entirely in four-dimensional quantum field theory, shares many features with holographic approaches: it appears intrinsically quantum mechanical; as an auxiliary fifth dimension Schwinger's proper time combines with the physical four spacetime dimensions into an AdS5 geometry; conformal-symmetry breaking contributions lead to warping; hidden local symmetry emerges; four-dimensional sources are extended to five-dimensional fields by a Wilson flow (gradient flow); and a variational principle for this flow reproduces the corresponding holographic calculation. The approach also yields the higher-dimensional description in the nonrelativistic case. © 2014 American Physical Society. Source


Grahl M.,Goethe University Frankfurt
Physical Review D - Particles, Fields, Gravitation and Cosmology | Year: 2014

The existence of a U(2)A×U(2)V-symmetric fixed point in the chiral linear sigma model is confirmed using the functional renormalization group. Its stability properties and the implications for the order of the chiral phase transition of two-flavor QCD are discussed. Furthermore, several technical conclusions are drawn from the comparison with the results of resummed loop expansions. © 2014 American Physical Society. Source


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

Holographic principles have impacted the way we look at strong coupling phenomena in quantum chromodynamics, strongly interacting extensions of the standard model, and condensed-matter physics. In real world settings, however, we still lack understanding of why and when such an approach is justified. Therefore, here, without invoking any such principle a priori, we demonstrate how such a picture arises in the worldline formulation of quantum field theory. Among other connections to holographic models, a warped AdS5 geometry, a quantum mechanical picture, and hidden local symmetry emerge, as well as a Wilson flow (gradient flow), which extends the four-dimensional sources to five-dimensional fields, and a link to the Gutzwiller trace formula. The worldline formulation also reproduces the nonrelativistic case, which is important for condensed-matter physics. © 2014 American Physical Society. Source


The high percentage of p53 missense mutations found in cancer has been attributed to mutant acquired oncogenic gain of functions. Different aspects of these tumour-promoting functions are caused by repression of the transcriptional activity of p53 family members p63 and p73. A subset of frequently occurring p53 mutations results in thermodynamic destabilisation of the DNA-binding domain (DBD) rendering this domain highly unstable. These conformational mutants (such as p53R175H) have been suggested to directly bind to p63 and p73 via a co-aggregation mechanism mediated by their DBDs. Although the DBDs of p63 and p73 are in fact not sufficient for the interaction as shown previously, we demonstrate here that the transactivation inhibitory (TI) domains within the α-isoform-specific C termini of p63 and p73 are essential for binding to p53R175H. Hence, the closed dimeric conformation of inactive TAp63α that renders the TI domain inaccessible prevents efficient interaction. We further show that binding to p53R175H correlates with an intrinsic aggregation propensity of the tetrameric α-isoforms conferred by an openly accessible TI domain again supporting interaction via a co-aggregation mechanism.Cell Death and Differentiation advance online publication, 22 July 2016; doi:10.1038/cdd.2016.75. © 2016 Macmillan Publishers Limited Source


Frisch S.,Goethe University Frankfurt
Frontiers in Human Neuroscience | Year: 2014

Three widespread assumptions of Cognitive-affective Neuroscience are discussed: first, mental functions are assumed to be localized in circumscribed brain areas which can be exactly determined, at least in principle (localizationism). Second, this assumption is associated with the more general claim that these functions (and dysfunctions, such as in neurological or mental diseases) are somehow generated inside the brain (internalism). Third, these functions are seen to be "biological" in the sense that they can be decomposed and finally explained on the basis of elementary biological causes (i.e., genetic, molecular, neurophysiological etc.), causes that can be identified by experimental methods as the gold standard (isolationism). Clinical neuropsychology is widely assumed to support these tenets. However, by making reference to the ideas of Kurt Goldstein (1878-1965), one of its most important founders, I argue that none of these assumptions is sufficiently supported. From the perspective of a clinical-neuropsychological practitioner, assessing and treating brain damage sequelae reveals a quite different picture of the brain as well as of us "brain carriers", making the organism (or person) in its specific environment the crucial reference point. This conclusion can be further elaborated: all experimental and clinical research on humans presupposes the notion of a situated, reflecting, and interacting subject, which precedes all kinds of scientific decomposition, however useful. These implications support the core assumptions of the embodiment approach to brain and mind, and, as I argue, Goldstein and his clinical-neuropsychological observations are part of its very origin, for both theoretical and historical reasons. © 2014 Frisch. Source


Szklarczyk R.,Maastricht University | Nooteboom M.,Radboud University Nijmegen | Osiewacz H.D.,Goethe University Frankfurt
Philosophical transactions of the Royal Society of London. Series B, Biological sciences | Year: 2014

Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria. © 2014 The Author(s) Published by the Royal Society. All rights reserved. Source


Weck F.,Goethe University Frankfurt
Psychiatric Quarterly | Year: 2014

Hypochondriasis is characterized by intensive fears of serious disease. Most patients with hypochondriasis worry about physical diseases like cancer, although in rare cases, patients report severe fears of mental disorders (e.g., schizophrenia), a phenomenon described in the literature as mental hypochondriasis. However, little is known about this rare subtype of hypochondriasis and experts have questioned whether mental hypochondriasis has much in common with the type of hypochondriasis in which somatic diseases are the focus of preoccupation. This paper presents, a case report of a woman with a fear of schizophrenia, which was treated with cognitive therapy. This patient fulfills the DSM-IV criteria of hypochondriasis and exhibits many characteristics (e.g., selective attention, safety behavior) considered to be maintaining factors in well-established cognitive-behavioral models of hypochondriasis. Cognitive treatment strategies for hypochondriasis (e.g., attention training, behavioral experiments) also proved effective in this case of mental hypochondriasis. © 2013 Springer Science+Business Media. Source


Betz B.,Goethe University Frankfurt | Gyulassy M.,Columbia University
Nuclear Physics A | Year: 2013

The nuclear modification factor R A measured in Pb + Pb collisions at the Large Hadron Collider (LHC) suggests that the jet-medium coupling in a Quark-Gluon Plasma at LHC energies is reduced as compared to energies reached at the Relativistic Heavy Ion Collider (RHIC). We estimate the reduction factor using a simple generic energy-loss model and find that the jet-medium coupling at the LHC is approximately 10% smaller than at RHIC. Moreover, we examine different jet-energy loss prescriptions with d E/d x ~ E a and show that the measured momentum dependence of the nuclear modification factor at the LHC rules out any model with E a >1/3. © 2013 Elsevier B.V. Source


Wicker S.,Goethe University Frankfurt | Maltezou H.C.,U.S. Center for Disease Control and Prevention
Expert Review of Vaccines | Year: 2014

During the second half of the 20th century, vaccinations led to the control or even eradication of several vaccine-preventable diseases (VPDs) in Europe. However, outbreaks of VPDs continue to occur even in countries with well-established vaccination programs. Reasons include the existence of under-vaccinated populations, the increasing anti-vaccination movement and the increasing movement of populations across borders. Ensuring adequate levels of herd immunity is the only reliable method for preventing epidemics and a re-emergence of VPDs. In order to achieve this, more flexible vaccine delivery platforms are needed targeting the less-privileged people, especially in the context of the current economic crisis. Healthcare personnel and healthcare systems should be prepared to address these challenges in the following years. © Informa UK, Ltd. Source


Hampel H.,Goethe University Frankfurt
International Psychogeriatrics | Year: 2012

The development of therapies for Alzheimer's disease (AD) presents numerous challenges for physicians, researchers, and the pharmaceutical industry, with many drug candidates showing promise at one stage of clinical research only to fall at the next hurdle. A great number of drugs with a variety of targets and clusters of mechanisms are currently in various stages of basic and clinical investigation. However, these hypothesis-derived agents may be tested much too late in the chronically progressive disease process to demonstrate meaningful effects or outcomes, mirroring the clinical syndromal scenario in which the underlying pathophysiological disease condition is frequently diagnosed extremely late. Moreover, the complexity of the disease calls for developments and improvements in study desig