@article{AhmedZeeshanHuberetal.2014, author = {Ahmed, Zeeshan and Zeeshan, Saman and Huber, Claudia and Hensel, Michael and Schomburg, Dietmar and M{\"u}nch, Richard and Eylert, Eva and Eisenreich, Wolfgang and Dandekar, Thomas}, title = {'Isotopo' a database application for facile analysis and management of mass isotopomer data}, series = {Database}, volume = {2014}, journal = {Database}, number = {bau077}, doi = {10.1093/database/bau077}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120102}, year = {2014}, abstract = {The composition of stable-isotope labelled isotopologues/isotopomers in metabolic products can be measured by mass spectrometry and supports the analysis of pathways and fluxes. As a prerequisite, the original mass spectra have to be processed, managed and stored to rapidly calculate, analyse and compare isotopomer enrichments to study, for instance, bacterial metabolism in infection. For such applications, we provide here the database application 'Isotopo'. This software package includes (i) a database to store and process isotopomer data, (ii) a parser to upload and translate different data formats for such data and (iii) an improved application to process and convert signal intensities from mass spectra of \(^{13}C\)-labelled metabolites such as tertbutyldimethylsilyl-derivatives of amino acids. Relative mass intensities and isotopomer distributions are calculated applying a partial least square method with iterative refinement for high precision data. The data output includes formats such as graphs for overall enrichments in amino acids. The package is user-friendly for easy and robust data management of multiple experiments.}, language = {en} } @article{RoyAssaadHerbut2014, author = {Roy, Bitan and Assaad, Fakher F. and Herbut, Igor F.}, title = {Zero Modes and Global Antiferromagnetism in Strained Graphene}, series = {Physical Review X}, volume = {4}, journal = {Physical Review X}, number = {2}, issn = {2160-3308}, doi = {10.1103/PhysRevX.4.021042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116108}, pages = {21042}, year = {2014}, abstract = {A novel magnetic ground state is reported for the Hubbard Hamiltonian in strained graphene. When the chemical potential lies close to the Dirac point, the ground state exhibits locally both the Neel and ferromagnetic orders, even for weak Hubbard interaction. Whereas the Neel order parameter remains of the same sign in the entire system, the magnetization at the boundary takes the opposite sign from the bulk. The total magnetization vanishes this way, and the magnetic ground state is globally only an antiferromagnet. This peculiar ordering stems from the nature of the strain-induced single-particle zero-energy states, which have support on one sublattice of the honeycomb lattice in the bulk, and on the other sublattice near the boundary of a finite system. We support our claim with the self-consistent numerical calculation of the order parameters, as well as by the Monte Carlo simulations of the Hubbard model in both uniformly and nonuniformly strained honeycomb lattice. The present result is contrasted with the magnetic ground state of the same Hubbard model in the presence of a true magnetic field (and for vanishing Zeeman coupling), which is exclusively Neel ordered, with zero local magnetization everywhere in the system.}, language = {en} } @article{EhrenschwenderBittnerSeiboldetal.2014, author = {Ehrenschwender, M. and Bittner, S. and Seibold, K. and Wajant, H.}, title = {XIAP-targeting drugs re-sensitize PIK3CA-mutated colorectal cancer cells for death receptor-induced apoptosis}, series = {Cell Death \& Disease}, volume = {5}, journal = {Cell Death \& Disease}, issn = {2041-4889}, doi = {10.1038/cddis.2014.534}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114374}, pages = {e1570}, year = {2014}, abstract = {Mutations in the oncogenic PIK3CA gene are found in 10-20\% of colorectal cancers (CRCs) and are associated with poor prognosis. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic TRAIL death receptor antibodies emerged as promising anti-neoplastic therapeutics, but to date failed to prove their capability in the clinical setting as especially primary tumors exhibit high rates of TRAIL resistance. In our study, we investigated the molecular mechanisms underlying TRAIL resistance in CRC cells with a mutant PIK3CA (PIK3CA-mut) gene. We show that inhibition of the constitutively active phosphatidylinositol-3 kinase (PI3K)/Akt signaling pathway only partially overcame TRAIL resistance in PIK3CA-mut-protected HCT116 cells, although synergistic effects of TRAIL plus PI3K, Akt or cyclin-dependent kinase (CDK) inhibitors could be noted. In sharp contrast, TRAIL triggered full-blown cell death induction in HCT116 PIK3CA-mut cells treated with proteasome inhibitors such as bortezomib and MG132. At the molecular level, resistance of HCT116 PIK3CA-mut cells against TRAIL was reflected by impaired caspase-3 activation and we provide evidence for a crucial involvement of the E3-ligase X-linked inhibitor of apoptosis protein (XIAP) therein. Drugs interfering with the activity and/or the expression of XIAP, such as the second mitochondria-derived activator of caspase mimetic BV6 and mithramycin-A, completely restored TRAIL sensitivity in PIK3CA-mut-protected HCT116 cells independent of a functional mitochondrial cell death pathway. Importantly, proteasome inhibitors and XIAP-targeting agents also sensitized other CRC cell lines with mutated PIK3CA for TRAIL-induced cell death. Together, our data suggest that proteasome-or XIAP-targeting drugs offer a novel therapeutic approach to overcome TRAIL resistance in PIK3CA-mutated CRC.}, language = {en} } @article{KellerSchultz2014, author = {Keller, Daniela Barbara and Schultz, J{\"o}rg}, title = {Word Formation Is Aware of Morpheme Family Size}, doi = {10.1371/journal.pone.0093978}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112848}, year = {2014}, abstract = {Words are built from smaller meaning bearing parts, called morphemes. As one word can contain multiple morphemes, one morpheme can be present in different words. The number of distinct words a morpheme can be found in is its family size. Here we used Birth-Death-Innovation Models (BDIMs) to analyze the distribution of morpheme family sizes in English and German vocabulary over the last 200 years. Rather than just fitting to a probability distribution, these mechanistic models allow for the direct interpretation of identified parameters. Despite the complexity of language change, we indeed found that a specific variant of this pure stochastic model, the second order linear balanced BDIM, significantly fitted the observed distributions. In this model, birth and death rates are increased for smaller morpheme families. This finding indicates an influence of morpheme family sizes on vocabulary changes. This could be an effect of word formation, perception or both. On a more general level, we give an example on how mechanistic models can enable the identification of statistical trends in language change usually hidden by cultural influences.}, language = {en} } @phdthesis{Roemer2014, author = {R{\"o}mer, Daniela}, title = {Where and how to build? Influence of social and environmental cues on nest building behavior in leaf-cutting ants}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109409}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2014}, abstract = {This thesis explores the influence of social and environmental cues on the nest building behavior of leaf-cutting ants. Especially, the investigations are aimed at evaluating the mechanisms of nest building and how the nest environment can spatially guide building responses that lead to an adaptive nest architecture. The emergence of nest chambers in the nest of the leaf-cutting ant Acromyrmex lundi were evaluated. Rather than excavating nest chambers in advance, at places where workers encounter suitable environmental conditions for brood and fungus rearing, these items have to be present at a site. When presented in the laboratory with a choice between two otherwise identical digging sites, offering suitable environmental conditions, but one containing brood, the workers displayed a higher excavation activity at the site where they encountered the putative content of a chamber. The shape of the excavated cavity was also more round and chamber-like. It is concluded that leaf-cutting ants respond to social cues during nest building. Excavation is a costly process and colonies have to spend a part of their energy stores on nest building, so that regulatory responses for the control of nest excavation are expected to occur. Worker density at the beginning of the digging process influenced digging activity while the presence of in-nest stores did not. Stored brood and fungus did however influence the architecture of the excavated nest, leading to the excavation of larger chambers and smaller tunnels. While self-organized mechanisms appear to be involved in the nest building process, the social cues of the ants' environment during building clearly influence the nest architecture and lead to an adjustment of the nest size to the current space needs of the colony. Workers secondarily regulated nest size by the opportunistic refilling of unused space with excavated soil pellets. As the ants should provide suitable conditions for brood and fungus rearing, they should show a behavioral response to CO2 concentrations, as the gas is known to hinder fungus respiration. Workers of A. lundi did indeed avoid high CO2-levels for fungus rearing but actually preferred CO2-values in the range encountered close to the soil surface, where this species excavates their nests. However, different CO2-levels did not affect their excavation behavior. While fungus chambers make up part of a leaf-cutting ant nest, most leaf-cutting ants of the genus Atta also spent part of the colony's energy on excavating large, voluminous chambers for waste disposal, rather than scattering the material aboveground. It is expected that leaf-cutting ants also show environmental preferences for waste management. In experiments Atta laevigata workers preferred deposition in a warm and dry environment and showed no preference for specific CO2-levels. The continued accumulation of waste particles in a waste chamber seems to be based on the use of volatiles. These originate from the waste itself, and seem to be used as an orientation cue by workers relocating the material. The ensuing large accumulation of waste at one site should result in the emergence of more voluminous chambers for waste disposal.}, subject = {Nestbau}, language = {en} } @article{KueblerHautzingerLudolphetal.2014, author = {K{\"u}bler, Andrea and Hautzinger, Martin and Ludolph, Albert and Dickhaus, Thorsten and Real, Ruben G. L.}, title = {Well-being in amyotrophic lateral sclerosis: a pilot experience sampling study}, doi = {10.3389/fpsyg.2014.00704}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-113057}, year = {2014}, abstract = {Objective: The aim of this longitudinal study was to identify predictors of instantaneous well-being in patients with amyotrophic lateral sclerosis (ALS). Based on flow theory well-being was expected to be highest when perceived demands and perceived control were in balance, and that thinking about the past would be a risk factor for rumination which would in turn reduce well-being. Methods: Using the experience sampling method, data on current activities, associated aspects of perceived demands, control, and well-being were collected from 10 patients with ALS three times a day for two weeks. Results: Results show that perceived control was uniformly and positively associated with well-being, but that demands were only positively associated with well-being when they were perceived as controllable. Mediation analysis confirmed thinking about the past, but not thinking about the future, to be a risk factor for rumination and reduced well-being. Discussion: Findings extend our knowledge of factors contributing to well-being in ALS as not only perceived control but also perceived demands can contribute to well-being. They further show that a focus on present experiences might contribute to increased well-being.}, language = {en} } @article{HerrmannBuckSchusteretal.2014, author = {Herrmann, Ken and Buck, Andreas K. and Schuster, Tibor and Abbrederis, Kathrin and Bl{\"u}mel, Christina and Santi, Ivan and Rudelius, Martina and Wester, Hans-J{\"u}rgen and Peschel, Christian and Schwaiger, Markus and Dechow, Tobias and Keller, Ulrich}, title = {Week one FLT-PET response predicts complete remission to R-CHOP and survival in DLBCL}, series = {Oncotarget}, volume = {5}, journal = {Oncotarget}, number = {12}, issn = {1949-2553}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120659}, pages = {4050-59}, year = {2014}, abstract = {Despite improved survival in the Rituximab (R) era, a considerable number of patients with diffuse large B-cell lymphoma (DLBCL) ultimately die from the disease. Functional imaging using [18F]fluorodeoxyglucose-PET is suggested for assessment of residual viable tumor very early during treatment but is compromised by non-specific tracer retention in inflammatory lesions. The PET tracer [18F]fluorodeoxythymidine (FLT) as surrogate marker of tumor proliferation may overcome this limitation. We present results of a prospective clinical study testing FLT-PET as superior and early predictor of response to chemotherapy and outcome in DLBCL. 54 patients underwent FLT-PET prior to and one week after the start of R-CHOP chemotherapy. Repetitive FLT-PET imaging was readily implemented into the diagnostic work-up. Our data demonstrate that the reduction of FLT standard uptake valuemean (SUVmean) and SUVmax one week after chemotherapy was significantly higher in patients achieving complete response (CR, n=48; non-CR, n=6; p<0.006). Martingale-residual and Cox proportional hazard analyses showed a significant monotonous decrease of mortality risk with increasing change in SUV. Consistent with these results, early FLT-PET response showed relevant discriminative ability in predicting CR. In conclusion, very early FLT-PET in the course of R-CHOP chemotherapy is feasible and enables identification of patients at risk for treatment failure.}, language = {en} } @article{KraftDrechslerGunrebenetal.2014, author = {Kraft, Peter and Drechsler, Christiane and Gunreben, Ignaz and Nieswandt, Bernhard and Stoll, Guido and Heuschmann, Peter Ulrich and Kleinschnitz, Christoph}, title = {Von Willebrand Factor Regulation in Patients with Acute and Chronic Cerebrovascular Disease: A Pilot, Case-Control Study}, series = {PLoS ONE}, volume = {9}, journal = {PLoS ONE}, number = {6}, issn = {1932-6203}, doi = {10.1371/journal.pone.0099851}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119588}, pages = {e99851}, year = {2014}, abstract = {Background and Purpose In animal models, von Willebrand factor (VWF) is involved in thrombus formation and propagation of ischemic stroke. However, the pathophysiological relevance of this molecule in humans, and its potential use as a biomarker for the risk and severity of ischemic stroke remains unclear. This study had two aims: to identify predictors of altered VWF levels and to examine whether VWF levels differ between acute cerebrovascular events and chronic cerebrovascular disease (CCD). Methods A case-control study was undertaken between 2010 and 2013 at our University clinic. In total, 116 patients with acute ischemic stroke (AIS) or transitory ischemic attack (TIA), 117 patients with CCD, and 104 healthy volunteers (HV) were included. Blood was taken at days 0, 1, and 3 in patients with AIS or TIA, and once in CCD patients and HV. VWF serum levels were measured and correlated with demographic and clinical parameters by multivariate linear regression and ANOVA. Results Patients with CCD (158±46\%) had significantly higher VWF levels than HV (113±36\%, P<0.001), but lower levels than AIS/TIA patients (200±95\%, P<0.001). Age, sex, and stroke severity influenced VWF levels (P<0.05). Conclusions VWF levels differed across disease subtypes and patient characteristics. Our study confirms increased VWF levels as a risk factor for cerebrovascular disease and, moreover, suggests that it may represent a potential biomarker for stroke severity, warranting further investigation.}, language = {en} } @phdthesis{Hoehn2014, author = {H{\"o}hn, Balthasar}, title = {Voluntary Interim Auditor Reviews and the Enforcement System in Germany}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-98957}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2014}, abstract = {Diese Dissertation behandelt das Thema der Finanzberichterstattung und Wirtschaftspr{\"u}fung. In einer allgemeinen Einleitung werden die gesetzlichen Grundlagen zur kapitalmarktorientierten Rechnungslegung und deren Kontrollen beschrieben. Als Folge des Bilanzkontrollgesetzes (BilKoG) wurde die Deutsche Pr{\"u}fstelle f{\"u}r Rechnungslegung (DPR) gegr{\"u}ndet. Diese privatrechtlich organisierte Kontrollinstanz pr{\"u}ft seit dem Jahr 2005 die Rechnungslegung von Unternehmen in Deutschland, die am regulierten Kapitalmarkt gelistet sind (Enforcement). Ziel ist es, eine wahrhafte und transparente Rechnungslegung im Interesse des Kapitalmarkts zu gew{\"a}hrleisten. Neben dem BilKoG wurde durch das am 20.01.2007 in Kraft getretene Transparenzrichtlinie-Umsetzungsgesetz (TUG) die Richtlinie 2004/109/EG in deutsches Recht transformiert. Ziel der EU-Transparenzrichtlinie war 'die Schaffung effizienter, integrierter und transparenter Wertpapierm{\"a}rkte, die Anleger und Kapitalgeber besser {\"u}ber die Finanzlage kapitalmarktorientierter Unternehmen informieren' (Henkel et al. (2008), S. 36). In der vorliegenden Arbeit werden in drei Studien spezielle Fragestellungen ausgehend von der gesetzlichen Entwicklung in Deutschland analysiert. Es werden die Zusammenh{\"a}nge zwischen freiwilligen Kontrollen eines Wirtschaftspr{\"u}fers, staatlichem Enforcement, Pr{\"u}fungskosten und Bilanzpolitik untersucht. Die erste Studie befasst sich mit der freiwilligen Kontrolle der Zwischenberichterstattung kapitalmarktorientierter Unternehmen. Die unterj{\"a}hrige Ver{\"o}ffentlichung von Zwischenberichten bietet entscheidungsrelevante und zeitnahe Informationen f{\"u}r Kapitalmarktakteure. Eine pr{\"u}ferische Durchsicht durch einen Wirtschaftspr{\"u}fer kann zus{\"a}tzliches Vertrauen in die Berichterstattung liefern. Bei der Implementierung des TUG wurde eine pflichtm{\"a}ßige pr{\"u}ferische Durchsicht von Zwischenberichten in Deutschland diskutiert. Der Gesetzgeber entschied sich gegen eine gesetzliche Verpflichtung und {\"u}bertrug die Entscheidung einer freiwilligen unterj{\"a}hrigen Kontrolle an Unternehmen und Wirtschaftspr{\"u}fer. Dieser Marktl{\"o}sung in Deutschland steht eine gesetzlich verpflichtete pr{\"u}ferische Durchsicht z.B. in den USA, Frankreich oder Australien gegen{\"u}ber. Es stellt sich folglich die Frage nach Kosten und Nutzen einer solchen Kontrollleistung, um die Vorteilhaftigkeit der gesetzlichen Pflicht oder der Marktl{\"o}sung zu bewerten. Diese erste Studie nutzt ausgehend vom TUG einen neu entstandenen, beobachtbaren Markt f{\"u}r pr{\"u}ferische Durchsichten in Deutschland. Die Kategorisierung der Pr{\"u}fungskosten in ‚Abschlusspr{\"u}fungskosten' und ‚Pr{\"u}fungsnahen Dienstleistungen' erm{\"o}glicht eine detaillierte Untersuchung der Kosten f{\"u}r das Unternehmen. Weiter wird der Nutzen in Bezug auf die Qualit{\"a}t der unterj{\"a}hrigen Berichterstattung analysiert. In der zweiten Studie wird das Angebot und die Nachfrage von pr{\"u}ferischen Durchsichten beleuchtet. In der Literatur werden die Agency-Kosten, die Corporate Governance Struktur und verschiedene Kostentreiber dieser Pr{\"u}fungsleistung als Einflussfaktoren identifiziert. Der positive Nachfrageschock bei pr{\"u}ferischen Durchsichten im Jahr 2007 l{\"a}sst sich durch diese Faktoren jedoch nicht erkl{\"a}ren. Ausgehend von der neu beobachtbaren Nachfrage stellt die Studie einen Zusammenhang zwischen dem erstmaligen Enforcement von Zwischenberichten durch die DPR und dem Inkrafttretens des TUG im Jahr 2007 her. Die gesetzlichen {\"A}nderungen werden dem theoretischen Rahmen von Angebot und Nachfrage freiwilliger externer Kontrollen zugeordnet. Im n{\"a}chsten Schritt wird der Einfluss von Fehlerentdeckungsrisiken durch die DPR f{\"u}r Management und Aufsichtsrat auf die Nachfrage von externen Kontrollen untersucht. Die dritte Studie befasst sich mit der Effektivit{\"a}t des deutschen Enforcement-Systems, dem Einfluss von Bilanzpolitik und dessen Antizipation in den Pr{\"u}fungskosten. Die Untersuchung analysiert den zeitlichen Aspekt von Bilanzpolitik auf Fehlerver{\"o}ffentlichungen in sp{\"a}teren Perioden. Es besteht die M{\"o}glichkeit die Verschlechterung der wirtschaftlichen Situation eines Unternehmens durch Bilanzpolitik zu verdecken. Ohne Verbesserung der wirtschaftlichen Lage des Unternehmens f{\"u}hrt dieses Verhalten zu einem Bilanzpolitikausmaß außerhalb des gesetzlichen Rahmens und folglich zu einer hohen Wahrscheinlichkeit der Fehlerentdeckung bei DPR Untersuchungen. Die Entwicklung der Bilanzpolitik eines solchen Unternehmens m{\"u}sste im zweiten Schritt mit der Risikokomponente in den Pr{\"u}fungskosten des Wirtschaftspr{\"u}fers in Verbindung stehen. Der risikoorientierte Pr{\"u}fungsansatz und die Antizipation von Bilanzpolitik in den Pr{\"u}fungskosten sollte demnach vor Fehlerbekanntmachung zu einem Anstieg der Pr{\"u}fungskosten f{\"u}hren. Zus{\"a}tzlich ist nach offizieller Fehlerver{\"o}ffentlichung und somit durch eine objektiv beobachtbare Schw{\"a}che im Rechnungslegungssystem oder einem hohen Ausmaß an Bilanzpolitik ein Risikoaufschlag zu vermuten. Der letzte Abschnitt fasst die wichtigsten Aussagen der Dissertation zusammen und erl{\"a}utert die Zusammenh{\"a}nge der Ergebnisse.}, subject = {Rechnungslegung}, language = {en} } @article{GrammatikosLangeSusseretal.2014, author = {Grammatikos, Georgios and Lange, Christian and Susser, Simon and Schwendy, Susanne and Dikopoulos, Nektarios and Buggisch, Peter and Encke, Jens and Teuber, Gerlinde and Goeser, Tobias and Thimme, Robert and Klinker, Hartwig and Boecher, Wulf O. and Schulte-Frohlinde, Ewert and Penna-Martinez, Marissa and Badenhoop, Klaus and Zeuzem, Stefan and Berg, Thomas and Sarrazin, Christoph}, title = {Vitamin D Levels Vary during Antiviral Treatment but Are Unable to Predict Treatment Outcome in HCV Genotype 1 Infected Patients}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {2}, issn = {1932-6203}, doi = {10.1371/journal.pone.0087974}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-117310}, pages = {e87974}, year = {2014}, abstract = {Background: Different parameters have been determined for prediction of treatment outcome in hepatitis c virus genotype 1 infected patients undergoing pegylated interferon, ribavirin combination therapy. Results on the importance of vitamin D levels are conflicting. In the present study, a comprehensive analysis of vitamin D levels before and during therapy together with single nucleotide polymorphisms involved in vitamin D metabolism in the context of other known treatment predictors has been performed. Methods: In a well characterized prospective cohort of 398 genotype 1 infected patients treated with pegylated interferon-alpha and ribavirin for 24-72 weeks (INDIV-2 study) 25-OH-vitamin D levels and different single nucleotide polymorphisms were analyzed together with known biochemical parameters for a correlation with virologic treatment outcome. Results: Fluctuations of more than 5 (10) ng/ml in 25-OH-vitamin D-levels have been observed in 66 (39) \% of patients during the course of antiviral therapy and neither pretreatment nor under treatment 25-OH-vitamin D-levels were associated with treatment outcome. The DHCR7-TT-polymorphism within the 7-dehydrocholesterol-reductase showed a significant association (P = 0.031) to sustained viral response in univariate analysis. Among numerous further parameters analyzed we found that age (OR = 1.028, CI = 1.002-1.056, P = 0.035), cholesterol (OR = 0.983, CI = 0.975-0.991, P<0.001), ferritin (OR = 1.002, CI = 1.000-1.004, P = 0.033), gGT (OR = 1.467, CI = 1.073-2.006, P = 0.016) and IL28B-genotype (OR = 2.442, CI = 1.271-4.695, P = 0.007) constituted the strongest predictors of treatment response. Conclusions: While 25-OH-vitamin D-levels levels show considerable variations during the long-lasting course of antiviral therapy they do not show any significant association to treatment outcome in genotype 1 infected patients.}, language = {en} }