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We develop a model of managerial compensation structure and asset risk choice. The model provides predictions about how inside debt features affect the relation between credit spreads and compensation components. First, inside debt reduces credit spreads only if it is unsecured. Second, inside debt exerts important indirect effects on the role of equity incentives: When inside debt is large and unsecured, equity incentives increase credit spreads; When inside debt is small or secured, this effect is weakened or reversed. We test our model on a sample of U.S. public firms with traded CDS contracts, finding evidence supportive of our predictions. To alleviate endogeneity concerns, we also show that our results are robust to using an instrumental variable approach.
We have studied one-proton-removal reactions of about 500MeV/u 17Ne beams on a carbon target at the R3B/LAND setup at GSI by detecting beam-like 15O-p and determining their relative-energy distribution. We exclusively selected the removal of a 17Ne halo proton, and the Glauber-model analysis of the 16F momentum distribution resulted in an s2 contribution in the 17Ne ground state of about 40%.
Sanctions placed upon airlines and other operators transporting persons without the required paperwork are called ‘carrier sanctions’. They constitute a key example of how border control mechanisms are currently being outsourced, privatized, delegated, and moved from the border itself to new physical locations. These practices can lead to a phenomenon referred to in this paper as ‘hidden coercion’. This paper argues that, while hidden coercion is commonplace in the reality of migration policy in most states, it is so far neglected in theoretical discussions of state coercion. Moreover, the discussion of carrier sanctions demonstrates that this neglect is problematic, since hidden coercion is not justifiable even within a framework that legitimizes state border coercion.
Examining event-related potential (ERP) correlates of decision bias in recognition memory judgments
(2014)
Memory judgments can be based on accurate memory information or on decision bias (the tendency to report that an event is part of episodic memory when one is in fact unsure). Event related potentials (ERP) correlates are important research tools for elucidating the dynamics underlying memory judgments but so far have been established only for investigations of accurate old/new discrimination. To identify the ERP correlates of bias, and observe how these interact with ERP correlates of memory, we conducted three experiments that manipulated decision bias within participants via instructions during recognition memory tests while their ERPs were recorded. In Experiment 1, the bias manipulation was performed between blocks of trials (automatized bias) and compared to trial-by-trial shifts of bias in accord with an external cue (flexibly controlled bias). In Experiment 2, the bias manipulation was performed at two different levels of accurate old/new discrimination as the memory strength of old (studied) items was varied. In Experiment 3, the bias manipulation was added to another, bottom-up driven manipulation of bias induced via familiarity. In the first two Experiments, and in the low familiarity condition of Experiment 3, we found evidence of an early frontocentral ERP component at 320 ms poststimulus (the FN320) that was sensitive to the manipulation of bias via instruction, with more negative amplitudes indexing more liberal bias. By contrast, later during the trial (500–700 ms poststimulus), bias effects interacted with old/new effects across all three experiments. Results suggest that the decision criterion is typically activated early during recognition memory trials, and is integrated with retrieved memory signals and task-specific processing demands later during the trial. More generally, the findings demonstrate how ERPs can help to specify the dynamics of recognition memory processes under top-down and bottom-up controlled retrieval conditions.
Evolutionary genetics of bears and red foxes over phylogenetic and phylogeographic time scales
(2014)
Climatic fluctuations during the Pleistocene (2.6-0.01 million years) have played an important role during evolution of many species. Cyclic range contractions and expansions had demographic consequences within species, provided environmental conditions for population divergence and speciation and enabled secondary contact and interspecific hybridization. These and other evolutionary processes have left genetic signatures in the genomes of affected organisms. Comprehensive and unbiased estimates of evolutionary processes can be obtained using genetic markers from different parts of the genome and by integrating population genetic and phylogenetic concepts.
Suitable for studies on evolutionary processes and patterns over different evolutionary time scales are bears (Ursidae) and foxes (Vulpes), which occupy a wide range of habitats and evolved during the past few millions of years. In my thesis, I therefore used bears and red foxes as study species to investigate the genetic variation within and between species and to obtain estimates of evolutionary relationships and divergence times of populations and species that I interpreted in a climatic context. Further, I investigated population genetic processes during the evolution of bears. My thesis includes three publications and one submitted manuscript, spanning different evolutionary time scales - from evolutionary relationships and processes among species (phylogenetic time scales, Publications I & II), among populations and closely related species in a geographical context (phylogeographic time scales, Publications II & III), to ongoing processes within species (population genetic time scales, Publication IV).
In Publication I (Kutschera et al. 2014, Mol Biol Evol 31(8):2004-2017), I studied bears at several nuclear markers from several individuals per species, complemented with markers from the Y chromosome. Using approaches based on a population genetic concept (coalescent theory) I obtained a species tree with divergence time estimates. Further, I studied two evolutionary processes in bears, interspecific gene flow and incomplete lineage sorting (ILS). This study contributed to the growing evidence that population genetic processes can be relevant on time scales up to several millions of years.
In Publication II (Hailer, Kutschera et al. 2012, Science 336(6079):344-347), we complemented previous mitochondrial (mt) DNA-based inference of the evolutionary history of polar and brown bears with nuclear DNA. Coalescence-based species tree analyses of multiple nuclear markers from several individuals per species placed polar bears as sister lineage to brown bears and their divergence time to about 600 thousand years ago (ka). This contrasted previous mtDNA-based inference. We explained this discrepancy between mtDNA and nuclear DNA with interspecific gene flow between polar and brown bears.
In Publication III (Kutschera et al. 2013, BMC Evol Biol 13:114), I studied range-wide phylogeographic events and their timing in red foxes. A synthesis of newly generated and published mtDNA sequences was analyzed using a coalescence-based approach with multiple fossil calibration points. Thereby, I validated the identity and geographic distribution of several red fox lineages and showed that red foxes colonized North America and Japan several times independently during the late Pleistocene (126-11 ka) and around the last glacial maximum (26.5-19 ka). In a comparison of my results from red foxes to brown bears and grey wolves, I identified similar phylogeographic patterns.
In Publication IV (Kutschera et al., submitted to Biol Conserv), I found similar levels of genetic variability in vagrant polar bears that had reached Iceland compared to established subpopulations from across the range. Based on climate projections reported by the Intergovernmental Panel on Climate Change in 2014, polar bear habitat will markedly decline and become increasingly fragmented within the next decades. Dispersal will play an important role by connecting isolated subpopulations, thereby maintaining genetic diversity levels. My results indicate that vagrants could stabilize genetic variability when immigrating into established subpopulations.
In conclusion, my thesis provided a deeper understanding of evolutionary genetic processes and patterns and their timing in bears and red foxes in a climatic context, which can have conservation implications. Further, I showed that processes like ILS and interspecific gene flow can be relevant over different time scales and are important aspects of evolutionary history. Thereby, my thesis contributed to the knowledge on the evolutionary history of several carnivore species and on evolutionary processes acting within and between closely related species.
We develop a methodology to identify and rank “systemically important financial institutions” (SIFIs). Our approach is consistent with that followed by the Financial Stability Board (FSB) but, unlike the latter, it is free of judgment and it is based entirely on publicly available data, thus filling the gap between the official views of the regulator and those that market participants can form with their own information set. We apply the methodology to annual data on three samples of banks (global, EU and euro area) for the years 2007-2012. We examine the evolution of the SIFIs over time and document the shifs in the relative weights of the major geographic areas. We also discuss the implication of the 2013 update of the identification methodology proposed by the FSB.
Event-by-event fluctuations of the mean transverse momentum of charged particles produced in pp collisions at s√ = 0.9, 2.76 and 7 TeV, and Pb-Pb collisions at sNN−−−−√ = 2.76 TeV are studied as a function of the charged-particle multiplicity using the ALICE detector at the LHC. Dynamical fluctuations indicative of correlated particle emission are observed in all systems. The results in pp collisions show little dependence on collision energy. The Monte Carlo event generators PYTHIA and PHOJET are in qualitative agreement with the data. Peripheral Pb-Pb data exhibit a similar multiplicity dependence as that observed in pp. In central Pb-Pb, the results deviate from this trend, featuring a significant reduction of the fluctuation strength. The results in Pb--Pb are in qualitative agreement with previous measurements in Au-Au at lower collision energies and with expectations from models that incorporate collective phenomena.
This study included 30 patients with diagnosed rheumatoid arthritis (RA) and 30 test subjects without RA (control group). The objective of the study was to examine both groups for the presence of temporomandibular disorders (TMD) and morphological changes of the temporomandibular joint (TMJ). All individuals were examined using a systematic detailed clinical TMD examination as well as magnetic resonance imaging (MRI). The clinical TMD examination yielded significant differences between the RA patients and the control group concerning crepitus of the TMJ, and palpation tenderness of the masticatory muscles as well as the unassisted mandibular opening. The evaluation of the MRI images for the RA group showed significantly more frequent deformations of the condyle, osteophyte formations and erosions in the condylar compacta, and degenerative changes in the spongiosa. Increased intra-articular accumulation of synovial liquid and signs of inflammatory changes of the spongiosa were only found in the RA group. Statistical analysis showed a significant correlation between crepitus and specific osteoarthrotic changes (MRI), respectively, and between crepitus and a complete anterior disk displacement without reduction (MRI). The duration of the RA disease correlated neither with the anamnestic and clinical dysfunction index by Helkimo nor with RA-specific MRI findings.
Evaluating model fit in nonlinear multilevel structural equation models (MSEM) presents a challenge as no adequate test statistic is available. Nevertheless, using a product indicator approach a likelihood ratio test for linear models is provided which may also be useful for nonlinear MSEM. The main problem with nonlinear models is that product variables are non-normally distributed. Although robust test statistics have been developed for linear SEM to ensure valid results under the condition of non-normality, they have not yet been investigated for nonlinear MSEM. In a Monte Carlo study, the performance of the robust likelihood ratio test was investigated for models with single-level latent interaction effects using the unconstrained product indicator approach. As overall model fit evaluation has a potential limitation in detecting the lack of fit at a single level even for linear models, level-specific model fit evaluation was also investigated using partially saturated models. Four population models were considered: a model with interaction effects at both levels, an interaction effect at the within-group level, an interaction effect at the between-group level, and a model with no interaction effects at both levels. For these models the number of groups, predictor correlation, and model misspecification was varied. The results indicate that the robust test statistic performed sufficiently well. Advantages of level-specific model fit evaluation for the detection of model misfit are demonstrated.
Surface disinfectants are part of broader preventive strategies preventing the transmission of bacteria, fungi and viruses in medical institutions. To evaluate their virucidal efficacy, these products must be tested with appropriate model viruses with different physico-chemical properties under conditions representing practical application in hospitals.
The aim of this study was to evaluate a quantitative carrier assay. Furthermore, different putative model viruses like adenovirus type 5 (AdV-5) and different animal parvoviruses were evaluated with respect to their tenacity and practicability in laboratory handling. To evaluate the robustness of the method, some of the viruses were tested in parallel in different laboratories in a multi-center study. Different biocides, which are common active ingredients of surface disinfectants, were used in the test. After drying on stainless steel discs as the carrier, model viruses were exposed to different concentrations of three alcohols, peracetic acid (PAA) or glutaraldehyde (GDA), with a fixed exposure time of 5 minutes. Residual virus was determined after treatment by endpoint titration.
All parvoviruses exhibited a similar stability with respect to GDA, while AdV-5 was more susceptible. For PAA, the porcine parvovirus was more sensitive than the other parvoviruses, and again, AdV-5 presented a higher susceptibility than the parvoviruses. All parvoviruses were resistant to alcohols, while AdV-5 was only stable when treated with 2-propanol. The analysis of the results of the multi-center study showed a high reproducibility of this test system.
In conclusion, two viruses with different physico-chemical properties can be recommended as appropriate model viruses for the evaluation of the virucidal efficacy of surface disinfectants: AdV-5, which has a high clinical impact, and murine parvovirus (MVM) with the highest practicability among the parvoviruses tested.
For centuries, it may have seemed as if standards of normative thinking now valid across the globe had first been instituted in Europe. These normative orders form the foundations of our verdicts that define and distinguish right and wrong, good and bad or even beautiful and ugly. But in order to better understand the global presence of such normative orders that evolved from within the European horizon, the history and implications of European expansion in the early modern era cannot be swept under the rug. ...
This chapter discusses whether and how 'new quantitative trade models' (NQTMs) can be fruitfully applied to quantify the welfare effects of trade liberalization, thus shedding light on the trade-related effects of further European integration. On the one hand, it argues that NQTMs have indeed the potential of being used to supplement traditional 'computable general equilibrium' (CGE) analysis thanks to their tight connection between theory and data, appealing micro-theoretical foundations, and enhanced attention to the estimation of structural parameters. On the other hand, further work is still needed in order to fully exploit such potential.
In this study prepared for the ECON Committee of the European Parliament, Gellings, Jungbluth and Langenbucher present a graphic overview on core legislation in the area of economic and financial services in Europe. The mapping overview can serve as background for further deliberations. The study covers legislation in force, proposals and other relevant provisions in fourteen policy areas, i.e. banking, securities markets and investment firms, market infrastructure, insurance and occupational pensions, payment services, consumer protection in financial services, the European System of Financial Supervision, European Monetary Union, Euro bills and Coins and statistics, competition, taxation, commerce and company law, accounting and auditing.
Markets are central to modern society, so their failures can have devastating effects. Here, we examine a prominent failure: price bubbles. We propose that bubbles are affected by ethnic homogeneity in the market and can be thwarted by diversity. Using experimental markets in Southeast Asia and North America, we find a marked difference: Market prices fit true values 58% better in diverse markets. In homogenous markets, overpricing is higher and traders’ errors are more correlated than in diverse markets. The findings suggest that price bubbles arise not only from individual errors or financial conditions, but also from the social context of decision making. Informing public discussion, our findings suggest that diversity facilitates friction that enhances deliberation and upends conformity.
We propose a new estimator for the spot covariance matrix of a multi-dimensional continuous semi-martingale log asset price process which is subject to noise and non-synchronous observations. The estimator is constructed based on a local average of block-wise parametric spectral covariance estimates. The latter originate from a local method of moments (LMM) which recently has been introduced by Bibinger et al. (2014). We extend the LMM estimator to allow for autocorrelated noise and propose a method to adaptively infer the autocorrelations from the data. We prove the consistency and asymptotic normality of the proposed spot covariance estimator. Based on extensive simulations we provide empirical guidance on the optimal implementation of the estimator and apply it to high-frequency data of a cross-section of NASDAQ blue chip stocks. Employing the estimator to estimate spot covariances, correlations and betas in normal but also extreme-event periods yields novel insights into intraday covariance and correlation dynamics. We show that intraday (co-)variations (i) follow underlying periodicity patterns, (ii) reveal substantial intraday variability associated with (co-)variation risk, (iii) are strongly serially correlated, and (iv) can increase strongly and nearly instantaneously if new information arrives.
Herbaceous ground vegetation is an important pool of biomass and nutrients, which is also used as the major forage source for wild ungulates. Up to now no standard methods exist to estimate herbaceous biomass on a landscape level for temperate forests, which are characterised by deciduous trees with closed canopies. Quantity and quality of the herbaceous forage accessible to herbivores can be estimated from estimated cover in vegetation plot data and information on biomass and element concentrations in plant species. Vegetation was sampled stratified by community types and forest developmental phases in Bavarian Forst National Park, Germany. We adopted the PhytoCalc model to estimate biomass and bioelement stocks from vegetation plot data and adjusted species assignments and absolute levels of biomass to the conditions in the national park. We categorised attractiveness of plant species as forage for red deer (Cervus elaphus) and roe deer (Capreolus capreolus). Multiple controls of total biomass and of plant groups (graminoids, ferns, herbs, Vaccinium, Rubus) were studied by stepwise regression against stand and environmental predictors. Herbaceous mass had a highly skewed distribution in the park, with 75% of plots having less than 231 g*m-2 of biomass or 24 g*m-2 of raw protein. Contributions of plant groups were site-dependent and variable, but decreased in the order Vaccinium-graminoids-Rubus-herbs-ferns. Biomass appeared to be controlled by deciduous tree cover, by total cover of canopy and coarse woody debris and by site quality, with nutrient-poor, high elevation sites having higher herb biomass. As a consequence, montane beech forests offered less forage mass than coniferous communities of high elevations and mires. Stand disturbances by bark beetles and the corresponding forest developmental phases had no systematic effects on total biomass.
Introduction: To determine the esthetic outcome of implant-based reconstructions after autologous and allogeneic bone grafting.
Methods: From 2003 to 2009, 67 patients underwent alveolar ridge augmentation and were enrolled in the study, 41 meet the inclusion criteria and 31 agreed to take part in the study. Patients were 18-69 years old (mean: 49.3 ± 13.8 years), and predominantly female. Patients received bone block grafts either autologous (n = 48) (AUBB) or allografts (ABB) (n = 19). Implants were inserted 4-7 months (autografts) or 5-6 months (allografts) after bone grafting. The Pink Esthetic Score (PES) as well as radiographic and subjective assessments were employed for the outcome analysis. The PES was assessed twice within one month based on digital photographic images that were randomly rearranged between evaluations by three independent, experienced investigators.
Results: Across all observations and investigators, the average PES was 7.5 ± 2.6 without differences between implants inserted in auto- and allografted bone, respectively. Patients assessed the allograft procedures as less painful and would have repeated it more often. The intra-rater reliability was excellent (correlation coefficients 0.7-0.9). The inter-observer agreement was lower (correlation coefficients 0.6-0.8).
Conclusions: Bone grafting with ABB allografts yields equivalent results to autologous grafting, and patients appreciate the omission of bone harvesting. The PES is a reliable method but should be performed by the same individual.
Die Dissertation besteht aus drei thematisch zusammenhängenden Forschungspapieren, in denen zeitstetige Konsum-, Investment- und Versicherungsprobleme über den Lebenszyklus betrachtet werden. Ein besonderer Fokus liegt auf realistischen Features wie stochastischem Sterberisiko und nicht-replizierbarem Einkommen. In der ersten Forschungsarbeit untersuche ich die Relevanz von stochastischem Sterberisiko. Dabei zeige ich, dass eine Sprungkomponente in der Sterberate die optimalen Entscheidungen der Agenten und das Wohlfahrtslevel signifikant beeinflusst. Eine Diffusionskomponente ist hingegen vernachlässigbar. In dem zweiten Forschungspapier untersuchen wir die Risikolebensversicherungsnachfrage einer Familie, dessen Alleinverdiener stochastischem Sterberisiko ausgesetzt ist. Wir achten insbesondere auf eine realistische Modellierung der Versicherung. Wir zeigen, dass dadurch junge Agenten dem Versicherungsmarkt fern bleiben und die Versicherungsnachfrage mit dem Alter steigt, im Gegensatz zu Modellen mit einfachen stetig-veränderbaren Versicherungen. Weiterhin verstärken langlaufende Versicherungsverträge die negativen Effekte von Einkommensschocks und werden daher von risikoaversen Agenten weniger abgeschlossen. In der dritten Forschungsarbeit untersuche ich die Critical Illness Versicherungsnachfrage eines Agenten in einem Modell mit stochastischem Sterberisiko und Gesundheitsausgaben. Die Versicherung übernimmt dabei die zusätzlichen Gesundheitskosten, die bei einem Sprung entstehen. Fast alle Agenten schließen solch eine Versicherung vor dem Rentenalter ab, selbst wenn diese sehr kostspielig ist. Insbesondere Agenten mit geringen Gesundheitsausgaben und hohem Einkommen haben eine hohe Versicherungsnachfrage.
Esiaba Irobi (1960-2010) was one of Africa's most innovative and productive younger playwrights. Deeply rooted in the indigenous performance traditions of his Igbo ethnic group, Irobi's drama, in the tradition of Wole Soyinka, is a hybrid production involving an iconoclastic reconceptualisation of the heritage he appropriates, its fascinating conflation with other performance traditions, and their projection onto the arena of contemporary Nigerian politics. This study by Isidore Diala is the first book-length examination of Irobi's work. It portrays a highly creative individual who was literally driven by the creative urge. The five chapters of this study illuminate different aspects of Irobi's oeuvre and include a vivid portrayal of Irobi the actor in his dream role of Elesin Oba, the eponymous King's Horseman in Wole Soyinka's drama. Diala highlight's Irobi's fascination for African festivals, which feature prominently in the earlier plays.He also demonstrates that although he is rooted in his Igbo culture, Irobi draws on different ethnic groups, pointing to conceptions of pan-Africanism that include the wAfrican diaspora.
The Swiss ophthalmologist Erika Sutter was born in Basel in 1917. She spent 32 years working in Elim Hospital, founded by the Swiss Mission in an impoverished rural area in North-Eastern South Africa. Together with her African colleague and friend, Selina Maphorogo, she founded the Care Groups, village self-help groups working for better health in their communities. The movement is still active after more than 30 years, and now has around 2,000 members, mostly women, in over 200 villages. Erika Sutter has received numerous international honours and awards for her pioneering work, including the award ?Woman of the Year? in 1984 from the South African newspaper ?The Star?, and an honorary doctorate from the University of Basel. For the creation of this biography, Erika Sutter spent many hours with the author, her friend Gertrud Stiehle, telling the story of her long life ? vividly, with a sharp eye for social issues, a hint of self-irony, and dry wit. Her account does not ignore events in the wider world. She experienced life on the Swiss-German border during the Second World War, and her years of working in South Africa were those when the apartheid policies of the South African Government were becoming more and more repressive, affecting many aspects of life in the country.
A 48 year old patient with dilated cardiomyopathy and chronic acne inversa underwent implantation of a LVAD system (Heartmate II, Thoratec, USA) March 2011. During 2011 and 2012 the patient was repeatedly readmitted for treatment of driveline infection with MRSA. Colonization was controlled with Linezolid and Rifampicin however reoccurred after discontinuation. In August 2012 the LVAD-system was exchanged due to pump dysfunction (HVAD, HeartWare Inc., USA). Postoperatively, the patient presented with ascites which secreted through the driveline exit. Consequently, the abdominal wall was surgically corrected to prevent exit of peritoneal fluid through the driveline, and the patient was discharged with sterile wound swabs. However 6 weeks after discharge the driveline exit wound started secreting pus showing abundant growth of multi resistant staphylococcus aureus (MRSA). With clinical signs of increasing liver failure with regular need for paracentesis, and clinical signs of local infection, a CT scan of the abdomen was performed revealing an enrichment of contrast medium along the driveline and an abscess-like formation on the abdominal wall. Patient was admitted receiving regular dose Daptomycin and Rifampicin. The latter was discontinued after ten days. The abscess, surrounding driveline exit and abdominal wall cavity was excised and vacuum treatment initiated. Total duration of Daptomycin therapy was 3 weeks. While first week skin and wound swabs were still positive for MRSA, all samples were sterile after the second week. Inflammation was monitored by leucocyte count and IL6. The secretion of pus along the driveline ceased, the wound cavity was closed subsequently. After discharge and stop of antibiotics skin and driveline swabs remained negative for MRSA (10 weeks).
We analyze the implications of the structure of a network for asset prices in a general equilibrium model. Networks are represented via self- and mutually exciting jump processes, and the representative agent has Epstein-Zin preferences. Our approach provides a exible and tractable unifying foundation for asset pricing in networks. The model endogenously generates results in accordance with, e.g., the robust-yetfragile feature of financial networks shown in Acemoglu, Ozdaglar, and Tahbaz-Salehi (2014) and the positive centrality premium documented in Ahern (2013). We also show that models with simpler preference assumptions cannot generate all these findings simultaneously.
Large herbivores are significant vectors for the long distance dispersal of seeds in various habitats, both attached to animals (epizoochory) and via gut passage (endozoochory). The majority of studies on epizoochory have examined dispersal in the fur of domesticated ungulates. Studies on wild ungulates are important to understand dispersal processes in many habitats, but rare due to methodological constraints. We studied epizoochory of seeds by European bison in an open-forest-mosaic (nutrient poor grassland and heathland, mixed forest) in NW Germany, where bison had been introduced for the purpose of nature conservation. At the study site it was possible to apply a method by which hoof material of freeranging bison was non-invasively collected. We identified a total of 1082 seeds from 32 plant species in the hoof material. The three most abundant species were Polygonum aviculare, Agrostis capillaris and Betula spp. Seed species originated from various habitat types of the study area, while the majority of seeds derived from trampled areas. Compared to the non-dispersed plant species of the study area, dispersed plant species had a higher seed longevity index, suggesting that many seeds were picked up from the soil seed bank. Epizoochory ranking indices of dispersed seed species, classifying the importance of epizoochory, revealed that transport in the fur may be of minor importance for many species, i.e. epizoochory by the hooves turned out to be negatively correlated to epizoochory in the fur. We conclude that European bison disperses a considerable number of seed species through trampling. Further research should consider epizoochory via the hooves and include integrative approaches to understand the different dispersal mechanisms by ungulates and their longterm synergetic effect on plant communities.
During embryonic development a large number of widely differing and specialized cell types with identical genomes are generated from a single totipotent zygote. Tissue specific transcription factors cooperate with epigenetic modifiers to establish cellular identity in differentiated cells and epigenetic regulatory mechanisms contribute to the maintenance of distinct chromatin states and cell-type specific gene expression patterns, a phenomenon referred to as epigenetic memory. This is accomplished via the stable maintenance of various epigenetic marks through successive rounds of cell division. Preservation of DNA methylation patterns is a well-established mechanism of epigenetic memory, but more recently it has become clear that many other epigenetic modifications can also be maintained following DNA replication and cell division. In this review, we present an overview of the current knowledge regarding the role of histone lysine methylation in the establishment and maintenance of stable epigenetic states.
Non-neuronal acetylcholine plays a substantial role in the human skin by influencing adhesion, migration, proliferation and differentiation of keratinocytes. These processes are regulated by the Mitogen-Activated Protein (MAP) kinase cascade. Here we show that in HaCaT keratinocytes all five muscarinic receptor subtypes are expressed, but M1 and M3 are the subtypes involved in mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to activation of the MAP kinase extracellular signal regulated kinase, together with the protein kinase Akt. The activation is fully dependent on the transactivation of the epidermal growth factor receptor (EGFR), which even appears to be the sole pathway for the muscarinic receptors to facilitate MAP kinase activation in HaCaT cells. The transactivation pathway involves a triple-membrane-passing process, based on activation of matrix metalloproteases, and extracellular ligand release; whereas phosphatidylinositol 3-kinase, Src family kinases or protein kinase C do not appear to be involved in MAP kinase activation. Furthermore, phosphorylation, ubiquitination and endocytosis of the EGF receptor after cholinergic transactivation are different from that induced by a direct stimulation with EGF, suggesting that ligands other than EGF itself mediate the cholinergic transactivation.
Epicutanoeus immunotherapy as a novel prophylactic and therapeutic strategy for birch pollen allergy
(2014)
The development of a convenient, effective and safe allergen-specific immunotherapy (SIT) for birch pollen allergy, one of the most prevalent allergic diseases in Northern Europe, North America and Northern Japan, is of crucial importance. Epicutaneous immunotherapy (EPIT) has gained attention as a safe and non-invasive alternative for subcutaneous immunotherapy, a conventional SIT. However, clinical studies showed a limited effcacy of EPIT, indicating the necessity of improvement of the treatment regime. In this study, we hypothesized that a combination of a hypoallergen with an appropriate adjuvant could be a strategy to improve EPIT. To verify this hypothesis, we aimed at investigating the efficacy of epicutaneous treatment with rBet v 1, the major birch pollen allergen, plus Toll-like receptor (TLR) agonists for prophylaxis and therapy of birch pollen allergy using a murine model of birch pollen-induced allergic asthma. Furthermore, the efficacy of rBet v 1B2, a hypoallergenic variant of Bet v 1, as a therapeutic allergen in EPI was pre-clinically investigated. TLRs recognize conserved microbial molecules (like PAMPs), and are known to promote the counter-regulation of TH2 responses by the induction of TH1-type and/or regulatory cytokines by immune cells. The hypoallergen Bet v 1B2 is a folding-variant of the wild-type allergen rBet v 1 with reduced allergenicity, but retained T-cell immunogenicity. The low allergenicity, could allow the application of hypoallergens in higher doses, and therefore provide a safer and more effective treatment to regulate T-cell immune responses. First, the expression and purification of recombinant Bet v 1 and Bet v 1B2 was optimized. Compared to natural proteins, recombinant proteins offer the possibility to use well-defined molecules with a consistent pharmaceutical quality. Using optimal Escherichia coli expression strains in combination with immobilized metal chelate affinity chromatography (IMAC) and size exclusion chromatography (SEC), we successfully prepared a large amount of rBet v 1 and rBet v 1B2 with a high purity. The allergenic potency of rBet v 1 and the hypoallergenic characteristics of rBet v 1B2 were confirmed by measurement of IgE reactivity and mediator release capacity using ELISA and basophil activation tests, respectively. In a second part, a murine model of birch pollen-induced allergic asthma was established. It was shown that intraperetoneal sensitization with an optimal dose of rBet v 1 and intranasal challenge with birch pollen extract induced elevated IgE levels, airway eosinophilia and pulmonary inflammation in BALB/c mice. The clinical features are comparable to those in patients with allergic asthma, indicating that sensitized and challenged mice could be used for a pre-clinical study to assess the efficacy of the treatment for birch pollen allergy. Next, we investigated the adjuvant effects of Polyadenylic:polyuridylic acid (Poly(A:U)), a TLR3 agonist, and R848 (resiquimod), a TLR7 agonist, in prophylactic EPI with rBet v 1 to intervene with birch pollen allergy. Here, we hypothesized that TLR3 and TLR7 could be possible target receptors to induce adjuvant effects in EPI, since these receptors are expressed in Langerhans cells and dermal dendritic cells, persistent antigen presenting cells in the cutaneous tissues. BALB/c mice received EPI with rBet v 1 alone, or plus Poly(A:U), or R848 on their depilated back using patches. Mice treated epicutaneously were then sensitized with rBet v 1 plus ALUM and intranasally challenged with birch pollen extract. We found that prophylactic EPI with rBet v 1 plus R848 inhibited the production of Bet v 1-specific IgE antibodies in sensitization, suppressed pulmonary inflammation and airway hyperreactivity upon challenge. In contrast to R848, no adjuvant effect of Poly(A:U) on suppression of asthmatic features was observed. Our results indicated that R848, but not Poly(A:U), could be a potential adjuvant for prophylactic EPI of birch pollen induced allergic asthma. Finally, the therapeutic potency of EPI with rBet v 1, or rBet v 1B2 alone, or plus R848 was assessed. After sensitization and challenge, mice received therapeutic EPI with rBet v 1 alone, or plus R848, and re-challenge with birch pollen extract. We found that therapeutic treatment with Bet v 1B2 reduced established Bet v 1-specific IgE antibodies, pulmonary inflammation and airway hyperreactivity upon re-challenge. Therapeutic treatment with the recombinant wild-type allergen does not influence these key characteristics of allergic asthma. In contrast to the findings in the prophylactic treatment with rBet v 1 plus R848,no therapeutic benefit was found upon combination with R848. This could be due to the high number of treatment days. Reduction of this number may lead to a beneficial effect. However, these findings indicate that Bet v 1B2 could be a potential therapeutic agent for the treatment of established birch pollen induced allergic asthma. In conclusion, this study demonstrates for the first time that prophylactic EPI with the recombinant form of Bet v 1 in combination with R848 could prevent and suppress asthmatic features in an established birch pollen allergy. Not only therapeutic, but also prophylactic applications of EPI could be of importance to prevent allergic sensitization, considering the high prevalence of allergic diseases. R848 could be a potential adjuvant for enhancing the prophylactic potential of EPI for the treatment of birch pollen allergy. Furthermore, the beneficial use of the hypoallergen Bet v 1B2 in therapeutic EPI was demonstrated by intervention of established asthmatic features. In the future, a combination of hypoallergens alone or together with adjuvants in EPIT could lead to a more convenient and effective therapeutic treatment of established birch pollen induced allergic asthma.
Central European dry grasslands are remarkably diverse plant communities that occur at the western edge of the Eurasian forest-steppe zone and harbour many species of continental distribution. Although their plant community types have been described in detail, the diversity patterns and their environmental determinants are still poorly known for these grasslands. Here, we study environmental drivers of species composition and richness in dry grasslands of northern Bohemia (České středohoří Mts) and central Bohemia (Křivoklát region), both in the Czech Republic. In vegetation plots of 100 m2 we recorded all vascular plant species, measured soil chemistry variables, above-ground biomass production and nutrient concentrations in biomass. Species richness in these plots ranged from 13 to 55. The relationships between species composition and the environment were explored using detrended correspondence analysis and canonical correspondence analysis, while the relationships between species richness and the environment were assessed using univariate and multiple regression models. In both regions, species composition and richness strongly responded to the soil pH (ranging from 4.0 to 7.8), which was positively correlated with calcium and magnesium concentrations and negatively with annual precipitation. The response of species richness to soil pH was unimodal with a peak at pH of about 6.5 in the České středohoří Mts, and positive in the Křivoklát region. Plots on soils with a pH higher than 5 consistently contained more than 35 species. In the České středohoří Mts, species richness was positively related to the aboveground biomass production, whereas in the Křivoklát region, this relationship was only significant for graminoid species. In both areas, plots with soils deeper than 20 cm and with aboveground biomass dry weight above 200 g/m2 harboured more than 40 species per 100 m2. Moreover, in the České středohoří Mts, nitrogen concentrations in the biomass had considerable effects on both species composition and richness: species numbers were lower at sites with higher nitrogen concentration. This indicates a threat to diversity of these dry grasslands under currently high atmospheric nitrogen deposition coupled with the absence of management at most of the studied sites.
In the last few decades, the abundance and importance of invasive alien species have grown continuously due to the undiminished growth of global trade. In most cases, arthropod introductions were unintended and occurred as hitchhikers or contaminants. Alien arthropods can have significant environmental impacts and can be economically costly. To measure these impacts, we expand a generic impact scoring system initially developed for mammals and birds, and applied it to terrestrial arthropods. It consists of six environmental impact categories and six economic impact categories, each with five impact levels. Information on impact was derived from an intensive analysis of published scientific literature. The scoring of the 77 most widely distributed arthropod species alien to Europe revealed the mite Varroa destructor as the most harmful species, followed by the Chinese longhorn beetle Anoplophora chinensis and the Argentine ant Linepithema humile. The highest environmental impact is through herbivory, disease transmission, and ecosystem impacts. The highest economic impact is on agriculture and human infrastructure and administration. The generic impact scoring system allows the impact scores of vertebrates and arthropods to be compared, thus serving as a background for the decision making processes of policy makers and stakeholders.
Background: Birch pollen-allergic subjects produce polyclonal cross-reactive IgE antibodies that mediate pollen-associated food allergies. The major allergen Bet v 1 and its homologs in plant foods bind IgE in their native protein conformation. Information on location, number and clinical relevance of IgE epitopes is limited. We addressed the use of an allergen-related protein model to identify amino acids critical for IgE binding of PR-10 allergens.
Method: Norcoclaurine synthase (NCS) from meadow rue is structurally homologous to Bet v 1 but does not bind Bet v 1-reactive IgE. NCS was used as the template for epitope grafting. NCS variants were tested with sera from 70 birch pollen allergic subjects and with monoclonal antibody BV16 reported to compete with IgE binding to Bet v 1.
Results: We generated an NCS variant (Δ29NCSN57/I58E/D60N/V63P/D68K) harboring an IgE epitope of Bet v 1. Bet v 1-type protein folding of the NCS variant was evaluated by 1H-15N-HSQC NMR spectroscopy. BV16 bound the NCS variant and 71% (50/70 sera) of our study population showed significant IgE binding. We observed IgE and BV16 cross-reactivity to the epitope presented by the NCS variant in a subgroup of Bet v 1-related allergens. Moreover BV16 blocked IgE binding to the NCS variant. Antibody cross-reactivity depended on a defined orientation of amino acids within the Bet v 1-type conformation.
Conclusion: Our system allows the evaluation of patient-specific epitope profiles and will facilitate both the identification of clinically relevant epitopes as biomarkers and the monitoring of therapeutic outcomes to improve diagnosis, prognosis, and therapy of allergies caused by PR-10 proteins.
Quarks and gluons are the building blocks of all hadronic matter, like protons and neutrons. Their interaction is described by Quantum Chromodynamics (QCD), a theory under test by large scale experiments like the Large Hadron Collider (LHC) at CERN and in the future at the Facility for Antiproton and Ion Research (FAIR) at GSI. However, perturbative methods can only be applied to QCD for high energies. Studies from first principles are possible via a discretization onto an Euclidean space-time grid. This discretization of QCD is called Lattice QCD (LQCD) and is the only ab-initio option outside of the high-energy regime. LQCD is extremely compute and memory intensive. In particular, it is by definition always bandwidth limited. Thus—despite the complexity of LQCD applications—it led to the development of several specialized compute platforms and influenced the development of others. However, in recent years General-Purpose computation on Graphics Processing Units (GPGPU) came up as a new means for parallel computing. Contrary to machines traditionally used for LQCD, graphics processing units (GPUs) are a massmarket product. This promises advantages in both the pace at which higher-performing hardware becomes available and its price. CL2QCD is an OpenCL based implementation of LQCD using Wilson fermions that was developed within this thesis. It operates on GPUs by all major vendors as well as on central processing units (CPUs). On the AMD Radeon HD 7970 it provides the fastest double-precision D= kernel for a single GPU, achieving 120GFLOPS. D=—the most compute intensive kernel in LQCD simulations—is commonly used to compare LQCD platforms. This performance is enabled by an in-depth analysis of optimization techniques for bandwidth-limited codes on GPUs. Further, analysis of the communication between GPU and CPU, as well as between multiple GPUs, enables high-performance Krylov space solvers and linear scaling to multiple GPUs within a single system. LQCD calculations require a sampling of the phase space. The hybrid Monte Carlo (HMC) algorithm performs this. For this task, a single AMD Radeon HD 7970 GPU provides four times the performance of two AMD Opteron 6220 running an optimized reference code. The same advantage is achieved in terms of energy-efficiency. In terms of normalized total cost of acquisition (TCA), GPU-based clusters match conventional large-scale LQCD systems. Contrary to those, however, they can be scaled up from a single node. Examples of large GPU-based systems are LOEWE-CSC and SANAM. On both, CL2QCD has already been used in production for LQCD studies.
The fluctuations in the ideal quantum gases are studied using the strongly intensive measures Δ[A,B] and Σ[A,B] defined in terms of two extensive quantities A and B. In the present Letter, these extensive quantities are taken as the motional variable, A=X, the system energy E or transverse momentum PT, and number of particles, B=N. This choice is most often considered in studying the event-by-event fluctuations and correlations in high energy nucleus–nucleus collisions. The recently proposed special normalization ensures that Δ and Σ are dimensionless and equal to unity for fluctuations given by the independent particle model. In statistical mechanics, the grand canonical ensemble formulation within the Boltzmann approximation gives an example of independent particle model. Our results demonstrate the effects due to the Bose and Fermi statistics. Estimates of the effects of quantum statistics in the hadron gas at temperatures and chemical potentials typical for thermal models of hadron production in high energy collisions are presented. In the case of massless particles and zero chemical potential the Δ and Σ measures are calculated analytically.
This paper investigates extensions of the method of endogenous gridpoints (ENDGM) introduced by Carroll (2006) to higher dimensions with more than one continuous endogenous state variable. We compare three different categories of algorithms: (i) the conventional method with exogenous grids (EXOGM), (ii) the pure method of endogenous gridpoints (ENDGM) and (iii) a hybrid method (HYBGM). ENDGM comes along with Delaunay interpolation on irregular grids. Comparison of methods is done by evaluating speed and accuracy. We find that HYBGM and ENDGM both dominate EXOGM. In an infinite horizon model, ENDGM also always dominates HYBGM. In a finite horizon model, the choice between HYBGM and ENDGM depends on the number of gridpoints in each dimension. With less than 150 gridpoints in each dimension ENDGM is faster than HYBGM, and vice versa. For a standard choice of 25 to 50 gridpoints in each dimension, ENDGM is 1.4 to 1.7 times faster than HYBGM in the finite horizon version and 2.4 to 2.5 times faster in the infinite horizon version of the model.
Emotions-at-risk: an experimental investigation into emotions, option prices and risk perception
(2014)
This paper experimentally investigates how emotions are associated with option prices and risk perception. Using a binary lottery, we find evidence that the emotion ‘surprise’ plays a significant role in the negative correlation between lottery returns and estimates of the price of a put option. Our findings shed new light on various existing theories on emotions and affect. We find gratitude, admiration, and joy to be positively associated with risk perception, although the affect heuristic predicts a negative association. In contrast with the predictions of the appraisal tendency framework (ATF), we document a negative correlation between option price and surprise for lottery winners. Finally, the results show that the option price is not associated with risk perception as commonly used in psychology.
We investigate the properties of the QCD matter across the deconfinement phase transition. In the scope of the parton-hadron string dynamics (PHSD) transport approach, we study the strongly interacting matter in equilibrium as well as the out-of equilibrium dynamics of relativistic heavy-ion collisions. We present here in particular the results on the electromagnetic radiation, i.e. photon and dilepton production, in relativistic heavy-ion collisions and the relevant correlator in equilibrium, i.e. the electric conductivity. By comparing our calculations for the heavy-ion collisions to the available data, we determine the relative importance of the various production sources and address the possible origin of the observed strong elliptic flow ν2 of direct photons.
These are exciting times for translational medicine as the convergence between fundamental and clinical research comes of age. The new EMBO Press publishing platform reinforces the standing of EMBO Molecular Medicine as the journal that matches high quality, novel research with rigorous editorial and ethical standards. It will also cement the journal's global reach and relevance - whether in highly active fields or explorative forays into emerging areas.
In mitochondria, biogenesis of oxidase is a crucial process involving the participation of an array of assembly factors. Studying the process of biogenesis in eukaryotes is highly complicated due to the presence and partaking of two genetic systems. Employing a bacterial model such as Paracoccus denitrificans that utilizes only one genetic system enables easy studying of the assembly process. The aa3 cytochrome c oxidase of P. denitrificans shows high structural and functional homology to its mitochondrial counterpart despite its simple subunit composition. The assembly of the core subunits I and II that house the active redox centers (heme a, and heme a3.CuB centre in subunit I; and the binuclear CuA centre in subunit II) along with the chaperons responsibly for their incorporation form the crux of this work. This work concentrates particularly on CtaG, a chaperone previously speculated to be involved in the delivery of copper to the CuB center in subunit I. As the full length structure of CtaG or its structural homologues have not been solved, attempts were made to obtain high-diffracting crystals of CtaG by heterologously expressing it in E. coli. Growth media, expression strains and induction parameters were some of the conditions screened in order to obtain optimal yield. Additives, pH and detergent were screened to yield a homogeneous preparation of CtaG. Crystallization trials were conducted by employing the sitting drop, vapour diffusion, method and later the bicelles were employed. Preliminary crystals obtained were further optimized employing seeding, detergent and additives, to improve diffraction. The diffraction improved from 30 Å to 15 Å. BN PAGE (Blue Native Polyacrylamide Gel Electrophoresis) analysis and cross-linking studies were undertaken to decipher the oligomeric condition of CtaG. Both the methods indicate that the protein is a dimer under native conditions. To study the importance of CtaG in the process of oxidase assembly, two deletion mutants were obtained from the lab; one with only ctaG deleted and the other with ctaG and most of the upstream ORF. The effect of the deletion was assayed on the assembly and activity of oxidase. The deletion mutants showed residual activity of approx. 20 %, while displaying a very low heme signal (both in membranes and in purified COX). In order to exclude polar effects arising due to gene manipulation, complementation strains were prepared, reintroducing ctaG alone into both the deletion strains. Complementation strains, where only ctaG was deleted and re-introduced assayed for COX activity showed a restoration in activity to approx. 70 %. Further, calculating the heme:protein ratio, the deletion strains displayed a value of 7 nmol/mg of oxidase which was increased to wild type levels of 16 nmol/mg in the complementation strains. To further confirm the absence of the copper in subunit I, total reflection X-ray fluorescence spectroscopy analysis was carried out, which showed a decrease in the copper content in the deletion strain, restored on complementation. The strain lacking in the ORF and ctaG when complemented with ctaG alone illustrated no increase in activity or heme signal in comparison to that of the deletion strain. These point at a possible role for ORF in the assembly of COX, which is still absent in the complementation strains. To further characterize the ORF, a series of bioinformatical analysis was carried out, the results from which were insufficient to characterize the ORF conclusively. In order to enlist the proteins involved in the biosynthesis of COX, two independent approaches were employed. Two-dimensional gel examinations of solubilised membranes from untreated and cross-linked cells were analyzed by Western blotting. The CtaG-COX interaction was observed in untreated membranes, which was additionally strengthened by cross-linking. To further confirm this association, pull-down assays were done employing protein A coated magnetic beads coated with different antibodies and incubated with solubilised membranes derived from untreated or cross-linked cells. The elutions were assayed by Western blotting and confirmed for the CtaG-COX interaction. These fractions were further analysed by mass spectrometry to identify other chaperons involved in biogenesis of oxidase. Along with CtaG, I also noticed Sco, Surf1c and other factors involved in the recruitment and transport of heme (CtaB, CtaA, and Ccm proteins). Interestingly, protein components of both ribosomal subunits and protein translocation factors were observed, which indicated a co-translational approach for co-factor insertion into COX.
Background: Long QT syndrome (LQTS) leads to arrhythmic events and increased risk for sudden cardiac death (SCD). Homozygous KCNH2 mutations underlying LQTS-2 have previously been termed "human HERG knockout" and typically express severe phenotypes. We studied genotype-phenotype correlations of an LQTS type 2 mutation identified in the homozygous index patient from a consanguineous Turkish family after his brother died suddenly during febrile illness.
Methods and Results: Clinical work-up, DNA sequencing, mutagenesis, cell culture, patch-clamp, in silico mathematical modelling, protein biochemistry, confocal microscopy were performed. Genetic analysis revealed a homozygous C-terminal KCNH2 mutation (p.R835Q) in the index patient (QTc ~506 ms with notched T waves). Parents were I° cousins – both heterozygous for the mutation and clinically unremarkable (QTc ~447 ms, father and ~396 ms, mother). Heterologous expression of KCNH2-R835Q showed mildly reduced current amplitudes. Biophysical properties of ionic currents were also only nominally changed with slight acceleration of deactivation and more negative V50 in R835Q-currents. Protein biochemistry and confocal microscopy revealed similar expression patterns and trafficking of WT and R835Q, even at elevated temperature. In silico analysis demonstrated mildly prolonged ventricular action potential duration (APD) compared to WT at a cycle length of 1000 ms. At a cycle length of 350 ms M-cell APD remained stable in WT, but displayed APD alternans in R835Q.
Conclusion: Kv11.1 channels affected by the C-terminal R835Q mutation display mildly modified biophysical properties, but leads to M-cell APD alternans with elevated heart rate and could precipitate SCD under specific clinical circumstances associated with high heart rates.
Recent density functional theory (DFT) calculations for KFe2As2 have been shown to be insufficient to satisfactorily describe angle-resolved photoemission (ARPES) measurements as well as observed de Haas–van Alphen (dHvA) frequencies. In the present work, we extend DFT calculations based on the full-potential linear augmented plane-wave method by dynamical mean field theory (DFT+DMFT) to include correlation effects beyond the local density approximation. We present results for two sets of reported crystal structures. Our calculations indicate that KFe2As2 is a moderately correlated metal with a mass renormalization factor of the Fe $3{\rm d}$ orbitals between 1.6 and 2.7. Furthermore, the obtained shape and size of the Fermi surface are in good agreement with ARPES measurements and we observe some topological changes with respect to DFT calculations such as the opening of an inner hole cylinder at the Z point. As a result, our calculated dHvA frequencies differ greatly from existing DFT results and qualitatively agree with experimental data. On this basis, we argue that correlation effects are important to understand the -presently under debate- nature of the superconducting state in KFe2As2.
Pulsed Electron Paramagnetic Resonance (EPR) spectroscopy is the most powerful tool to investigate structural properties and dynamics of paramagnetic substances. Up to date the electron spin is almost exclusively manipulated by rectangular shaped microwave pulses generated with switches. These pulses are unselective which means they excite outside their nominal bandwidth which is in most cases shallow compared to the overall spectral width of the spin system. Shaped pulses which are widely applied in NMR promise higher bandwidth and selectivity. The use of amplitude and phase modulated pulses was not possible for EPR due to the three orders of magnitude faster timescale compared to NMR. In this work, for the first time, an AWG (arbitrary waveform generator) operating with a 1 ns time resolution and 14 bit amplitude resolution was implemented into a commercial Bruker pulsed EPR spectrometer.
First results were obtained with broadband excitation pulses derived by optimum control theory (OCT). The OCT-pulse used excites transverse magnetization with 98% efficiency over a more than four times larger bandwidth than common rectangular pulse generating the same 1 B field. The benefit of such a pulse was demonstrated for magnitude FT-EPR spectroscopy on organic radicals in liquid phase.
Due to Spectrometer deadtime an FID cannot be observed for most inhomogeneous spin systems. For that reason prefocused pulses have been evaluated for their applicability to EPR spectroscopy. OCT-derived prefocused pulses can be understood as a compact Hahn Echo sequence in one monolithic pulse. Here, two problems have been encountered. 1) The limited bandwidth of the active and passive microwave components in the excitation path as well as microwave resonator cause linear distortions of the pulse shape which results in inferior pulse performance. This could be circumvented by measuring the impulse response function of the whole spin excitation path and including this information in the pulse optimization procedure. 2) Anisotropic hyperfine interaction which was not taken into account during the pulse optimization also caused efficiency losses.
PELDOR spectroscopy is a valuable tool to measure distance distributions between two or more paramagnetic centers in the range from 2-8 nm. It is demonstrated that the S/N ratio of PELDOR experiments can be substantially increased by substituting the rectangular shaped pump pulse by an adiabatic inversion pulse. The damping of the dipolar oscillations introduced by the prolonged pump pulse towards shorter distances could be circumvented by introducing a second time reversed pump pulse.
By substituting the refocused echo of the well-known 4-pulse PELDOR with a CPMG sequence the dipolar evolution time and thus the validity of PELDOR experiments would be increased. To achieve the maximum dipolar evolution time in a CPMG PELDOR for each refocusing pulse one pump pulse has to be applied. This could only be achieved with the new adiabatic inversion pulses since multiple inversions with efficiency close to one are not possible with rectangular pulses. Even with adiabatic pump pulses a reduced efficiency was observed due to hardware limitations thus limiting the sequence to three refocusing pulses. An iterative method was developed to remove the residual dipolar signals attributed to the reduced inversion efficiency.
The new 7-pulse CPMG PELDOR sequence enabled measuring reliable distance distributions between the protomers of the trimeric betaine transporter BetP. With these it could be shown that the asymmetries found for the 2 and 3-dimensional crystal structures are even larger in frozen detergent.
Electromagnetic calorimeter (ECAL) is being developed to complement dilepton spectrometer HADES. ECAL will enable the HADES@FAIR experiment to measure data on neutral meson production in heavy ion collisions at the energy range of 2-10 AGeV on the beam of future accelerator SIS100@FAIR. We will report results of the last beam test with quasi-monoenergetic photons carried out in MAMI facility at Johannes Gutenberg Universität Mainz.
Recent data on status and distribution of resident and migrant birds in the Cape Verde Islands are presented, including records of nine taxa new to the archipelago, viz. Ciconia nigra, Ciconia ciconia, Circus macrourus, Falco naumanni, Chlidonias hybrida, Chlidonias leucopterus, Apus affinis, Ptyonoprogne fuligula and Phylloscopus inornatus. Also presented are data on a number of breeding taxa, including the first record of the endemic Cape Verde purple heron Ardea bournei outside Santiago island. The alarming situation of the magnificent frigatebird Fregata magnificens, of which only three individuals remain in Cape Verde, constituting the entire population in the East Atlantic, remains of great concern. Several species of birds of prey are also highly threatened and have already become extinct in some islands. Following its expansion through Northwest Africa and the Canary Islands, Eurasian collared dove Streptopelia decaocto has now also become established in at least three of the Cape Verde Islands.
Information theory allows us to investigate information processing in neural systems in terms of information transfer, storage and modification. Especially the measure of information transfer, transfer entropy, has seen a dramatic surge of interest in neuroscience. Estimating transfer entropy from two processes requires the observation of multiple realizations of these processes to estimate associated probability density functions. To obtain these necessary observations, available estimators typically assume stationarity of processes to allow pooling of observations over time. This assumption however, is a major obstacle to the application of these estimators in neuroscience as observed processes are often non-stationary. As a solution, Gomez-Herrero and colleagues theoretically showed that the stationarity assumption may be avoided by estimating transfer entropy from an ensemble of realizations. Such an ensemble of realizations is often readily available in neuroscience experiments in the form of experimental trials. Thus, in this work we combine the ensemble method with a recently proposed transfer entropy estimator to make transfer entropy estimation applicable to non-stationary time series. We present an efficient implementation of the approach that is suitable for the increased computational demand of the ensemble method's practical application. In particular, we use a massively parallel implementation for a graphics processing unit to handle the computationally most heavy aspects of the ensemble method for transfer entropy estimation. We test the performance and robustness of our implementation on data from numerical simulations of stochastic processes. We also demonstrate the applicability of the ensemble method to magnetoencephalographic data. While we mainly evaluate the proposed method for neuroscience data, we expect it to be applicable in a variety of fields that are concerned with the analysis of information transfer in complex biological, social, and artificial systems.
We propose an iterative procedure to efficiently estimate models with complex log-likelihood functions and the number of parameters relative to the observations being potentially high. Given consistent but inefficient estimates of sub-vectors of the parameter vector, the procedure yields computationally tractable, consistent and asymptotic efficient estimates of all parameters. We show the asymptotic normality and derive the estimator's asymptotic covariance in dependence of the number of iteration steps. To mitigate the curse of dimensionality in high-parameterized models, we combine the procedure with a penalization approach yielding sparsity and reducing model complexity. Small sample properties of the estimator are illustrated for two time series models in a simulation study. In an empirical application, we use the proposed method to estimate the connectedness between companies by extending the approach by Diebold and Yilmaz (2014) to a high-dimensional non-Gaussian setting.
Objective: Advanced or recurrent endometrial cancer (EC) no longer amenable to surgery or radiotherapy is a life-threatening disease with limited therapeutic options left. Eighty percent of ECs express receptors for luteinizing hormone-releasing hormone (LHRH), which can be targeted by AEZS-108 (zoptarelin doxorubicin acetate). This phase 2 trial was performed to assess the efficacy and safety of AEZS-108 in this group of patients.
Methods: Patients had FIGO (Fédération Internationale de Gynécologie et d'Obstétrique) III or IV or recurrent EC, LHRH receptor-positive tumor status, and at least had 1 measurable lesion (Response Evaluation Criteria in Solid Tumors). Prior anthracycline therapy was not allowed. Patients received AEZS-108 as a 2-hour infusion on day 1 of a 21-day cycle. The treatment was continued for a maximum of 6 to 8 cycles. The primary end point was the response rate determined by the Response Evaluation Criteria in Solid Tumors.
Results: From April 2008 to November 2009, 44 patients were included in the study at 8 centers in Germany (AGO) and 3 centers in Bulgaria. Forty-three of these patients were eligible. Two (5%) patients had a complete remission, and 8 (18%) achieved a partial remission. Stable disease for at least 6 weeks was observed in 44%. The median time to progression was 7 months, and the median overall survival was 15 months. The most frequently reported grade 3 or 4 adverse effects were neutropenia (12%) and leucopenia (9%).
Conclusions: AEZS-108, an LHRH-agonist coupled to doxorubicin, has significant activity and low toxicity in women with advanced or recurrent LHRH receptor-positive EC, supporting the principle of receptor-mediated targeted chemotherapy.
Fluctuations of the water level at the edges of temporary water bodies provide favourable living conditions for annual plant communities of the phytosociological class Isoëto-Nanojuncetea. Such communities of periodically flooded ponds within the agricultural landscape of NE Germany are particularly rich in rare plant species of that class. During the past decades drainage, fertilisation and herbicides in the surrounding arable fields have led to a severe decline in diversity of these species. To develop efficient conservation strategies it is essential to understand the factors driving the species composition. Therefore, we studied how varying water regimes, soil properties and agricultural practices affect the diversity and species composition of these temporary ponds. The study was carried out in seven ponds on a conventionally managed farm in NE Brandenburg. At each of these wetlands mixed soil samples were taken to determine the pH, total nitrogen and phosphorus concentration. The plant species were recorded in 177 plots, each covering 1 x 1 m2. For each plot, the water level was recorded in April, July and August 2013, respectively, resulting in five "water level regimes". Total species number and percentages of Isoëto-Nanojuncetea species were determined per plot, to evaluate water level effects on the vegetation. In addition, mean Ellenberg indicator values for light, moisture and nutrients were calculated to assess the environmental conditions.
Background: Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication.
Findings: Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages.
Conclusions: These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity.
Background: Low Emission Zones (LEZs) are areas where the most polluting vehicles are restricted from entering. The effectiveness of LEZs to lower ambient exposures is under debate. This study focused on LEZs that restricted cars of Euro 1 standard without appropriate retrofitting systems from entering and estimated LEZ effects on NO2, NO, and NOx ( = NO2+NO).
Methods: Continuous half-hour and diffuse sampler 4-week average NO2, NO, and NOx concentrations measured inside and outside LEZs in 17 German cities of 6 federal states (2005–2009) were analysed as matched quadruplets (two pairs of simultaneously measured index values inside LEZ and reference values outside LEZ, one pair measured before and one after introducing LEZs with time differences that equal multiples of 364 days) by multiple linear and log-linear fixed-effects regression modelling (covariables: e.g., wind velocity, amount of precipitation, height of inversion base, school holidays, truck-free periods). Additionally, the continuous half-hour data was collapsed into 4-week averages and pooled with the diffuse sampler data to perform joint analysis.
Results: More than 3,000,000 quadruplets of continuous measurements (half-hour averages) were identified at 38 index and 45 reference stations. Pooling with diffuse sampler data from 15 index and 10 reference stations lead to more than 4,000 quadruplets for joint analyses of 4-week averages. Mean LEZ effects on NO2, NO, and NOx concentrations (reductions) were estimated to be at most −2 µg/m3 (or −4%). The 4-week averages of NO2 concentrations at index stations after LEZ introduction were 55 µg/m3 (median and mean values) or 82 µg/m3 (95th percentile).
Conclusions: This is the first study investigating comprehensively the effectiveness of LEZs to reduce NO2, NO, and NOx concentrations controlling for most relevant potential confounders. Our analyses indicate that there is a statistically significant, but rather small reduction of NO2, NO, and NOx concentrations associated with LEZs.
This essay reviews a cornerstone of the European Banking Union project, the resolution of systemically important banks. The focus is on the inherent conflict between a possible intervention by resolution authorities, conditional on a crisis situation, and effective prevention prior to a crisis. Moreover, the paper discusses the rules for bail-in debt and conversion rules for different layers of debt. Finally, some organizational requirements to achieve effective resolution results will be analyzed.
Objective: To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.
Design: Systematic review and meta-analysis of individual patient data.
Data sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.
Eligibility: Randomized controlled trials comparing immunosuppressive regimens with and without sirolimus in recipients of kidney or combined pancreatic and renal transplant for which the author was willing to provide individual patient level data. Two reviewers independently screened titles/abstracts and full text reports of potentially eligible trials to identify studies for inclusion. All eligible trials reported data on malignancy or survival.
Results: The search yielded 2365 unique citations. Patient level data were available from 5876 patients from 21 randomized trials. Sirolimus was associated with a 40% reduction in the risk of malignancy (adjusted hazard ratio 0.60, 95% confidence interval 0.39 to 0.93) and a 56% reduction in the risk of non-melanoma skin cancer (0.44, 0.30 to 0.63) compared with controls. The most pronounced effect was seen in patients who converted to sirolimus from an established immunosuppressive regimen, resulting in a reduction in risk of malignancy (0.34, 0.28 to 0.41), non-melanoma skin cancer (0.32, 0.24 to 0.42), and other cancers (0.52, 0.38 to 0.69). Sirolimus was associated with an increased risk of death (1.43, 1.21 to 1.71) compared with controls.
Conclusions: Sirolimus was associated with a reduction in the risk of malignancy and non-melanoma skin cancer in transplant recipients. The benefit was most pronounced in patients who converted from an established immunosuppressive regimen to sirolimus. Given the risk of mortality, however, the use of this drug does not seem warranted for most patients with kidney transplant. Further research is needed to determine if different populations, such as those at high risk of cancer, might benefit from sirolimus.
Ternary aerosol nucleation experiments were conducted in the CLOUD chamber at CERN in order to investigate the influence of ions on new particle formation. Neutral and ion-induced nucleation experiments, i.e., with and without the presence of ions, were carried out under precisely controlled conditions. The sulphuric acid concentration was measured with a Chemical Ionization Mass Spectrometer (CIMS) during the new particle formation experiments. The added ternary trace gases were ammonia (NH3), dimethylamine (DMA, C2H7N) or oxidised products of pinanediol (PD, C10H18O2). When pinanediol was introduced into the chamber, an increase in the mass spectrometric signal used to determine the sulphuric acid concentration (m/z 97, i.e., HSO4−) was observed due to ions from the CLOUD chamber. The enhancement was only observed during ion-induced nucleation measurements by using either galactic cosmic rays (GCR) or the proton synchrotron (PS) pion beam for the ion generation, respectively. The ion effect typically involved an increase in the apparent sulphuric acid concentration by a factor of ~2 to 3 and was qualitatively verified by the ion measurements by an Atmospheric Pressure interface-Time Of Flight (APi-TOF) mass spectrometer. By applying a high voltage (HV) clearing field inside the CLOUD chamber the ion effect on the CIMS measurement was completely eliminated since, under these conditions, small ions are swept from the chamber in about one second. In order to exclude the ion effect and to provide corrected sulphuric acid concentrations during the GCR and PS beam nucleation experiments, a parameterisation was derived that utilizes the trace gas concentrations and the UV light intensity as input parameters. Atmospheric sulphuric acid measurements with a CIMS showed an insignificant ion effect.
Ternary aerosol nucleation experiments were conducted in the CLOUD chamber at CERN in order to investigate the influence of ions on new particle formation. Neutral and ion-induced nucleation experiments, i.e. without and with the presence of ions, respectively, were carried out under precisely controlled conditions. The sulfuric acid concentration was measured with a chemical ionisation mass spectrometer (CIMS) during the new particle formation experiments. The added ternary trace gases were ammonia (NH3), dimethylamine (DMA, C2H7N) or oxidised products of pinanediol (PD, C10H18O2). When pinanediol was introduced into the chamber, an increase in the mass spectrometric signal used to determine the sulfuric acid concentration (m/z 97, i.e. HSO4−) was observed due to ions from the CLOUD chamber. The enhancement was only observed during ion-induced nucleation measurements by using either galactic cosmic rays (GCRs) or the proton synchrotron (PS) pion beam for the ion generation, respectively. The ion effect typically involved an increase in the apparent sulfuric acid concentration by a factor of ~ 2 to 3 and was qualitatively verified by the ion measurements with an atmospheric-pressure interface-time of flight (APi-TOF) mass spectrometer. By applying a high-voltage (HV) clearing field inside the CLOUD chamber, the ion effect on the CIMS measurement was completely eliminated since, under these conditions, small ions are swept from the chamber in about 1 s. In order to exclude the ion effect and to provide corrected sulfuric acid concentrations during the GCR and PS beam nucleation experiments, a parameterisation was derived that utilises the trace gas concentrations and the UV light intensity as input parameters. Atmospheric sulfuric acid measurements with a CIMS showed an insignificant ion effect.
Purpose: To evaluate the effect of chronic liver disease (CLD) in a multivariate analysis of associated risk factors in patients with hepatocellular carcinoma (HCC) using transarterial chemoembolization (TACE). Materials and methods: A total of 145 patients with HCC (99 men, 46 women; mean age: 63 years ±8.1; age range: 46-84 years) underwent 598 TACE procedures. The presence of CLD, number and location of lesions, tumor size, Child-Pugh score, vascularity, portal involvement and alpha fetoprotein value were analyzed using the multivariate regression model. Cox regression was used for survival analysis. Results: The median survival time was 26.7 months, and 78.6% of all treated lesions showed tumor responses. The presence of CLD (OR 2.12, P=0.004), Child-Pugh score B (OR 2.24, P=0.002), alpha fetoprotein >100ng/dl (OR 1.18, P<0.001), multinodularity (≥3 lesions) (OR 4.41, P=0.003), lesion size >5cm (OR 4.12, P=0.002) and hypervascularity (OR 7.94, P=0.003) were significant effective factors for a local response when analyzed using a multivariate logistic model. Multivariate survival analysis using Cox's regression model during the median follow-up period of 25 months (range: 1-42 months) demonstrated a significant difference in survival rates (P values <0.05). No significant difference in responses was noted for males, locations of lesions and portal involvements statistically. Conclusion: The presence of chronic liver disease as well as associated risk factors including Child-Pugh score B, alpha fetoprotein 100ng/dl, multinodularity (≥3 lesions), lesion size >5cm and hypervascularity statistically led to a significant effect in tumor response in HCC patients treated with TACE. Patient gender, location of lesion and involvement of portal vein showed no significant difference in response.
Background: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS.
Design: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred.
Summary: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
Physics at its core is an experimental pursuit. If one theory does not agree with experimental results, then the theory is wrong. However, it is becoming harder and harder to directly test some theories of fundamental physics at the high energy/small distance frontier exactly because this frontier is becoming technologically harder to reach. The Large Hadron Collider is getting near the limit of what we can do with present accelerator technology in terms of directly reaching the energy frontier. The motivation for this special issue was to try and collect together ideas and potential approaches to experimentally probe some of our ideas about physics at the high energy/small distance frontier. Some of the papers in this special issue directly deal with the issue of what happens to spacetime at small distance scales. In the paper by A. Aurilia and E. Spallucci a picture of quantum spacetime is given based on the effects of ultrahigh velocity length contractions on the structure of the spacetime. The work of P. Nicolini et al. further pursues the idea that spacetime has a minimal length. The consequences of this minimal length are investigated in terms of the effects it would have on the gravitational collapse of a star to form a black hole. In the article by G. Amelino-Camelia et al. the quantum structure of spacetime is studied through the Fermi LAT data on the Gamma Ray Burst GRB130427A. The article by S. Hossenfelder addressed the question of whether spacetime is fundamentally continuous or discrete and postulates that in the case when spacetime is discrete it might have defects which would have important observational consequences. ...
(Micro)plastics in the aquatic environment are an issue of emerging concern. However, to date, there is considerable lack of knowledge on the abundance and toxicity of plastic debris in aquatic ecosystems, especially with regard to the freshwater situation. In this editorial, we briefly discuss important aspects of the research on environmental (micro)plastics to stimulate research and call for papers.
The Paddys River Wetlands in the New South Wales Southern Highlands, southwest of Sydney, are characterised by several watercourses with associated swamps (fens), some of which, on Forestry Corporation of NSW land, have been the focus for removal of Pinus radiata wildings by the Penrose Swamps Conservation Group. In this study we map a population of Eucalyptus aquatica trees in one of these swamps perched above Paddys River (latitude 34.65575o S, longitude 150.21831o E; 600 m elevation). Eucalyptus aquatica is geographically restricted to the Paddys River area and is listed as a threatened species at state and national levels. New findings on the physical characteristics of the swamp in relation to the bedrock geology, stream geomorphology, peat development and the main native plant species, are presented. The occurrence of clumps of Eucalyptus aquatica appears to be independent of the type or thickness of the growing substrate. Rather it is suggested that a continuous supply of water and the shelter afforded by the narrow valley may be key factors determining the distribution of the trees at the study site. An on-going programme of research is underway to study other occurrences of Eucalyptus aquatica.
The Virgin Islands (except St. Croix) are geologically part of the Puerto Rico Bank and biologically related to Puerto Rico, but their cockroaches (Dictyoptera: Blattaria) were not yet as well studied as those on Puerto Rico. To elucidate the number of species, life history, range distribution, and seasonal abundance of these cockroaches, we have conducted a quantitative study since June 2000 using a Malaise trap on Guana Island, British Virgin Islands, in addition to other conventional collecting methods. We found 21 species: Blattella germanica (Linnaeus), Cariblatta antiguensis (Saussure and Zehntner), Cariblatta sp. 2, Cariblatta sp. 3, Colapteroblatta sp. 1, Eurycotis improcera Rehn, Eurycotis sp. 2, Euthlastoblatta facies (Walker), Hemiblabera brunneri (Saussure), Nyctibora lutzi Rehn and Hebard, Panchlora sagax Rehn and Hebard, Periplaneta americana (Linnaeus), P. australasiae (Fabricius), Plectoptera infulata Rehn and Hebard, P. rhabdota Rehn and Hebard, Plectoptera sp. 3, Pycnoscelus surinamensis (Linnaeus), Symploce pararufi collis Roth, S. rufi collis (Fabricius), polyphagid sp. 1 (Compsodes sp. 1), and polyphagid sp. 2. Among them, nine are new records for the Virgin Islands and fi ve for Guana Island. In addition, Euthlastoblatta diaphana (Fabricius), Nyctibora noctivaga Rehn, Panchlora nivea (Linnaeus), P. viridis (Fabricius), and Rhyparobia maderae (Fabricius) were recorded historically but were not rediscovered. As a result, the number of species is increased from 17 to 26 for the Virgin Islands, and from 10 to 15 for Guana Island. Overall, only fi ve species are edifi carian and likely introduced. Nymphs of polyphagid sp. 2 and Euthlastoblatta facies are reported for the fi rst time as dwellers in termite runways. Only eight species came to the Malaise trap; their phenology illustrates close but not necessarily synchronic relationship with both the timing and amount of rainfall. Monthly abundance showed spring and fall highs and summer and winter lows. Yearly abundance reached lows when annual rainfall decreased below a threshold average of 2.0 mm per day. Seasonality and response to drought varied among species. This paper lays a foundation for further research on diversity of cockroaches from the Virgin Islands and their relationships with those from Puerto Rico.
The scope of this Thesis is to understand the position dependency phenomenon of human visual perception. First, under the ecological assumption, meaning under the assumption that animals adapt to the statistical regularities of their environment, we study the consequences of the imaging on the local statistics of the input to the human visual system. Second, we model efficient representations of these statistics and their contribution to shape the properties of eye sensory neurons. Third, we model efficient representations of the semantic context of images and the correctness of different underneath geometrical assumptions on the statistics of images.
The efficient coding hypothesis posits that sensory systems are adapted to the regularities of their signal input in order to reduce redundancy in the resulting representations. It is therefore important to characterize the regularities of natural signals to gain insight into the processing of natural stimuli. While measurements of statistical regularity in vision have focused on photographic images of natural environments it has been much less investigated, how the specific imaging process embodied by the organism’s eye induces statistical dependencies on the natural input to the visual system. This has allowed using the convenient assumption that natural image data is homogeneous across the visual field. Here we give up on this assumption and show how the imaging process in a human eye model influences the local statistics of the natural input to the visual system across the entire visual field. ...
Objective: Acute kidney injury (AKI) after cardiac surgery procedures is associated with poor patient outcomes. Cystatin C as a marker for renal failure has been shown to be of prognostic value; however, a wide range of its predictive accuracy has been reported. The aim of the study was to evaluate whether the measurement of pre- and postoperative serum cystatin C improves the prediction of AKI.
Methods: In a single-centre, prospective study of 70 patients (74 ± 9ys; range 47-85ys; 77% male), cystatin C was measured six times: (T1 = preoperative, T2 = start cardiopulmonary bypass (CPB), T3 = 20 min after CPB, T4 = end of operation; T5 = 24 h postoperatively; T6 = 7d postoperatively). Predictive property, in terms of the need for renal replacement therapy (RRT), was analysed by receiver operating characteristics (ROC) statistics and described by the area under the curve (AUC).
Results: With respect to RRT (n = 8), serum cystatin C was significantly higher at the end of the operation (T4), 24 h postoperatively at T5 and at T6. The AUCs for preoperative T1 and intraoperative T2/3 cystatin C were <0.7 (95% CI, 0.47-0.85). The earliest significant predictive AUCs were found at the end of the operation (T4: p = 0.03 95% CI 0.58-0.88 AUC 0.73) and 24 h postoperatively (T5: p = 0.003 95% CI 0.74-0.96 AUC 0.85).
Conclusions: Early postoperative serum cystatin C increase appears to be a moderate biomarker in the prediction of AKI, whereas a preoperative and intraoperative cystatin C increase has only a limited diagnostic and predictive value.
Background: High-intensity focused ultrasound (HIFU) allows to inflict intracorporal thermal lesions without penetrating the skin or damaging the surrounding tissue. This analysis intends to assess the magnitude of HIFU-induced ablations within benign thyroid nodules using scintigraphic imaging with 99mTc.
Methods: Ten cold, hot, or indifferent nodules were treated using multiple pulses of HIFU to induce temperatures of around 85°C within the ablation zone. Pre- and posttreatment, uptake values of 99mTc pertechnetate or 99mTc-MIBI were recorded. The pre-post reduction of nodular uptake was evaluated to assess ablation magnitude.
Results: Relative nodular uptake in relation to total thyroidal uptake decreased after one session of HIFU in all cases. Median 99mTc-MIBI uptake reduction was 35.5% (ranging from 11% to 57%; p < 0.1), while 99mTc-pertechnetate scintigraphy showed a median uptake reduction of 27% (range 10% to 44%; p < 0.1). No major complications were observed.
Conclusions: HIFU appears to be safe and is an easy to perform means of thermal ablation. This study shows that HIFU treatment in thyroidal nodules can be evaluated by scintigraphic means shortly after the intervention. Due to small sample size, the exact magnitude of HIFU ablation efficiency in thyroidal nodules remains a value to beassessed in a larger study.
During cell stress, the transcription and translation of immediate early genes are prioritized, while most other messenger RNAs (mRNAs) are stored away in stress granules or degraded in processing bodies (P-bodies). TIA-1 is an mRNA-binding protein that needs to translocate from the nucleus to seed the formation of stress granules in the cytoplasm. Because other stress granule components such as TDP-43, FUS, ATXN2, SMN, MAPT, HNRNPA2B1, and HNRNPA1 are crucial for the motor neuron diseases amyotrophic lateral sclerosis (ALS)/spinal muscular atrophy (SMA) and for the frontotemporal dementia (FTD), here we studied mouse nervous tissue to identify mRNAs with selective dependence on Tia1 deletion. Transcriptome profiling with oligonucleotide microarrays in comparison of spinal cord and cerebellum, together with independent validation in quantitative reverse transcriptase PCR and immunoblots demonstrated several strong and consistent dysregulations. In agreement with previously reported TIA1 knock down effects, cell cycle and apoptosis regulators were affected markedly with expression changes up to +2-fold, exhibiting increased levels for Cdkn1a, Ccnf, and Tprkb vs. decreased levels for Bid and Inca1 transcripts. Novel and surprisingly strong expression alterations were detected for fat storage and membrane trafficking factors, with prominent +3-fold upregulations of Plin4, Wdfy1, Tbc1d24, and Pnpla2 vs. a −2.4-fold downregulation of Cntn4 transcript, encoding an axonal membrane adhesion factor with established haploinsufficiency. In comparison, subtle effects on the RNA processing machinery included up to 1.2-fold upregulations of Dcp1b and Tial1. The effect on lipid dynamics factors is noteworthy, since also the gene deletion of Tardbp (encoding TDP-43) and Atxn2 led to fat metabolism phenotypes in mouse. In conclusion, genetic ablation of the stress granule nucleator TIA-1 has a novel major effect on mRNAs encoding lipid homeostasis factors in the brain, similar to the fasting effect.
Dynamics of juvenile woody plant communities on termite mounds in a West African savanna landscape
(2014)
Termites are keystone species in savanna ecology, and their mounds are thought to be an important source of habitat heterogeneity and structural complexity of the savanna. Macrotermes termitaria have been shown to allow woody plant colonisation of landscapes otherwise dominated by C4 grasses. In this study, we assess how resource-rich Macrotermes mounds affect juvenile woody plant and non-woody plant species diversity, community composition, biomass and population dynamics. We repeatedly sampled paired termite mound and savanna plots in Pendjari National Park (Sudanian vegetation zone, North Benin, West Africa) over the course of two years. Despite considerable overlap in their species pools, plant communities of mound and savanna plots were clearly separated in ordinations. Species richness and diversity of juvenile woody plants was consistently higher on termite mounds, while no differences could be detected for non-woody plants. Evenness of juvenile woody plants was generally lower on mounds, whereas density and basal area were higher on mounds. In contrast, we did not detect any influence of the mound microhabitat on colonisation, mortality and turnover of woody juveniles. Therefore, we suggest that differences in the communities on and off mounds should be strongly influenced by directed diaspore dispersal through zoochory.
The ability to delay gratification, to wait for a larger but delayed reward in the presence of a smaller but constantly available reward, has been shown to be predictive for various aspects of everyday life. For instance, preschool children who were better able to delay gratification achieved better school grades, a higher education, a better ability to cope with stress, as well as a reduced risk for being overweight or consume drugs up to 30 years later (Mischel et al., 2011). However, despite the importance of delay of gratification cognitive factors underlying individual differences are only poorly understood. Wittmann and Paulus (2008) suggested that individuals who overestimate the duration of time intervals experience waiting times as more costly and are, therefore, less likely to delay gratification. Furthermore, a recent study revealed an association between less accurate internal clock speed and a behavioral choice delay task (Corvi, Juergensen, Weaver, & Demaree, 2012). Further evidence for an association between temporal processing and delay of gratification can be derived from studies using clinical samples. For instance, children with attention-deficit/hyperactivity disorder (ADHD) consistently prefer smaller, immediate rewards over larger, delayed rewards and show impaired temporal processing (Sonuga-Barke, Bitsakou, & Thompson, 2010). However, no study has directly tested an association between a measure of temporal processing and a classical delay of gratification task in children with and without ADHD so far.
As part of a larger study, 64 children (29 with ADHD) aged between 8 to 12 years performed a version of an auditory duration discrimination task and a delay of gratification task. In the duration discrimination task, the children were presented with two unfilled intervals indicated by two brief tones each. The baseline interval lasted for 400 ms, while the comparison interval was always longer and adjusted up or down in 10 ms steps securing an accuracy of 80%. In the delay of gratification task, the children were instructed that they could either opt for one chocolate bar immediately or that they could wait to receive two chocolate bars. Unbeknownst to the children, the waiting time lasted 25 minutes but children were told that they could decide for the immediate chocolate bar at any time by ringing a bell.
Children with ADHD did not differ in their performance from children without ADHD in the duration discrimination task or the delay of gratification task. However, in the whole sample of children with and without ADHD, children who waited for the additional chocolate bar showed a better duration discrimination than children who failed to wait for the additional chocolate bar [t(62) = -2.52, p = .01].
We demonstrated an association between temporal processing ability and the ability to delay gratification. These results need to be replicated in further studies with larger sample sizes. Moreover, different tasks measuring temporal processing and delay of gratification should be used to further clarify the relationship of temporal processing, delay of gratification, and ADHD.
We present the data of the 2nd research expedition of the European Dry Grassland Group (EDGG), which was conducted in 2010 in Central Podolia, Ukraine. The aim was to collect plot data to compare Ukrainian dry grasslands with those of other parts of Europe in terms of syntaxonomy and biodiversity. We sampled 21 nested-plot series (0.0001–100 m2) and 184 normal plots (10 m2) covering the full variety of dry grassland types occurring in the study region. For all plots, we recorded species composi-tion of terrestrial vascular plants, bryophytes and lichens, while for the 226 10-m2 plots we estimated and measured percentage cover of all species, structural, topographic, soil and landuse parameters. The 10-m² plots were used for phytosociological classification based on iteratively refined TWINSPAN classification as well as for DCA ordination. Differences between the derived vegetation types with respect to environmental conditions and species richness were assessed with ANOVAs. We assigned our plots to nine association-level units but refrained from placing them into formal associations with two exceptions. In the study area, dry grasslands of the Festuco-Brometea were far more common than those of the Koelerio-Corynephoretea. Among the Festuco-Brometea, xeric Festucetalia valesiacae grasslands were more frequent and represented by the Festucion valesiacae (2 associations, including the Allio taurici-Dichanthietum ischaemi ass. nova) and the Stipion lessingianae (1) compared to the Brachypodietalia pinnati with the Agrostio vinealis-Avenulion schellianae (3). The Koelerio-Corynephoretea were represented by three associations, each from a different order and alliance: basiphilous outcrops (Alysso alyssoidis-Sedetalia: Alysso alyssoidis-Sedion?), acidophilous outcrops (Sedo-Scleranthetalia: Veronico dillenii-Sedion albi?) and mesoxeric sandy grasslands (Trifolio arvensis-Festucetalia ovinae: Agrostion vinealis). We discuss the issue of the mesoxeric order Galietalia veri placed within the Molinio-Arrhenatheretea by Ukrainian authors and conclude that the content of that order would probably be better placed in the mesoxeric orders of the Koelerio-Corynephoretea and Festuco-Brometea. Other syntaxonomic questions could not be solved with our geographically limited dataset and await a supraregional analysis, e.g. whether the Ukrainian outcrop communities should be assigned to the same alliances as known from Central Europe or rather represent new vicariant units. The analysis of the biodiversity patterns showed that at a grain size of 10 m2, Podolian Koelerio-Corynephoretea communities were overall richer than Festuco-Brometea communities (46.4 vs. 40.6 species). This difference was due to the Koelerio-Corynephoretea containing twice as many bryophytes and nine times more lichens, while vascular plant species richness did not differ significantly between classes. The orders within the classes showed no real differences in species richness. The richness patterns observed in Podolia were almost the opposite of those usually found in dry grasslands, where Brachypodietalia pinnati are richer than Festucetalia valesiacae, and these richer than stands of the Koelerio-Corynpehoretea – and we do not have a good explanation for these idiosyncrasies. In conclusion, Podolian dry grasslands behave quite unexpectedly regarding biodiversity, and their syntaxonomy is still poorly understood. These knowledge gaps can only be addressed with supranational analyses based on comprehensive datasets.
The diagnosis of drug induced liver injury (DILI) is based primarily on the exclusion of alternative causes. To assess the frequency of alternative causes in initially suspected DILI cases, we searched the Medline database with the following terms: drug hepatotoxicity, drug induced liver injury, and hepatotoxic drugs. For each term, we used the first 100 publications. We reviewed references, selected those reports relevant to our study, and retrieved finally 15 publications related to DILI and alternative causes. A total of 2,906 cases of initially assumed DILI were analyzed in these 15 publications, with diagnoses missed in 14% of the cases due to overt alternative causes. In another 11%, the diagnosis of DILI could not be established because of confounding variables. Alternative diagnoses included hepatitis B, C, and E, CMV, EBV, ischemic hepatitis, autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, hemochromatosis, Wilson’s disease, Gilbert’s syndrome, fatty liver, non alcoholic steatohepatitis, alcoholic liver diseases, cardiac and thyroid causes, rhabdomyolysis, polymyositis, postictal state, tumors, lymphomas, chlamydial and HIV infections. Causality assessment methods applied in these 15 publications were the CIOMS (Council for International Organizations of Medical Sciences) scale alone (n = 5) or combined with the Maria and Victorino (MV) scale (n = 1), the DILIN (Drug-Induced Liver Injury Network) method (n = 4), or the Naranjo scale (n = 1); the qualitative CIOMS method alone (n = 3) or combined with the MV scale (n = 1). In conclusion, alternative diagnoses are common in primarily suspected DILI cases and should be excluded early in future cases, requiring a thorough clinical and causality assessment.
Causality assessment of suspected drug induced liver injury (DILI) and herb induced liver injury (HILI) is hampered by the lack of a standardized approach to be used by attending physicians and at various subsequent evaluating levels. The aim of this review was to analyze the suitability of the liver specific Council for International Organizations of Medical Sciences (CIOMS) scale as a standard tool for causality assessment in DILI and HILI cases. PubMed database was searched for the following terms: drug induced liver injury; herb induced liver injury; DILI causality assessment; and HILI causality assessment. The strength of the CIOMS lies in its potential as a standardized scale for DILI and HILI causality assessment. Other advantages include its liver specificity and its validation for hepatotoxicity with excellent sensitivity, specificity and predictive validity, based on cases with a positive reexposure test. This scale allows prospective collection of all relevant data required for a valid causality assessment. It does not require expert knowledge in hepatotoxicity and its results may subsequently be refined. Weaknesses of the CIOMS scale include the limited exclusion of alternative causes and qualitatively graded risk factors. In conclusion, CIOMS appears to be suitable as a standard scale for attending physicians, regulatory agencies, expert panels and other scientists to provide a standardized, reproducible causality assessment in suspected DILI and HILI cases, applicable primarily at all assessing levels involved.
Driving change : the story of the South Africa Norway tertiary education development programme
(2014)
Driving Change tells a story that exemplifies a basic law of physics, known to all - the application of a relatively small lever can shift weight, create movement and initiate change far in excess of its own size. It tells a story about a particular instance of development cooperation, relatively modest in scope and aim that has nonetheless achieved remarkable things and has been held up as an exemplar of its kind. It does not tell a story of flawless execution and perfectly achieved outcomes: it is instead a narrative that gives some insight into the structural and organisational arrangements, the institutional and individual commitments, and above all, the work, intelligence and passion of its participants, which made the SANTED Programme a noteworthy success.
Does the rotten child spoil his companion? : spatial peer effects among children in rural India
(2014)
This paper identifies the effect of neighborhood peer groups on childhood skill acquisition using observational data. We incorporate spatial peer interaction, defined as a child's nearest geographical neighbors, into a production function of child cognitive development in Andhra Pradesh, India. Our peer group definition takes the form of networks, whose structure allows us to identify endogenous peer effects and contextual effects separately. We exploit variation over time to avoid confounding correlated with social effects. Our results suggest that spatial peer and neighborhood effects are strongly positively associated with a child's cognitive skill formation. Further, we explore the effect of peer groups in helping to provide insurance against the negative impact of idiosyncratic shocks to child learning. We find that the data reject full risk-sharing, but cannot rule out the existence of partial risk-sharing on behalf of peers. We show that peer effects are robust to different specifications of peer interactions and investigate the sensitivity of our estimates to potential misspecification of the network structure using Monte Carlo experiments.
Two alternative hypotheses – referred to as opportunity- and stigma-based behavior – suggest that the magnitude of the link between unemployment and crime also depends on preexisting local crime levels. In order to analyze conjectured nonlinearities between both variables, we use quantile regressions applied to German district panel data. While both conventional OLS and quantile regressions confirm the positive link between unemployment and crime for property crimes, results for assault differ with respect to the method of estimation. Whereas conventional mean regressions do not show any significant effect (which would confirm the usual result found for violent crimes in the literature), quantile regression reveals that size and importance of the relationship are conditional on the crime rate. The partial effect is significantly positive for moderately low and median quantiles of local assault rates.
Regulation of investor access to financial products is often based on product familiarity indicated by previous use. The underlying premise that lack of familiarity with a product class causes unwarranted participation is difficult to test. This paper uses household-level data from the ‘experiment’ of German reunification that (exogenously) offered to East Germans access to capitalist products (exogenously) unfamiliar to them. We compare the evolution of post-unification participation of former East and West Germans in financial products, controlling for relevant household characteristics. We vary familiarity differentials by considering (i) both unfamiliar ‘capitalist’ products (stocks, bonds, and consumer credit) and ones available in the East (savings accounts and life insurance); and (ii) cohorts with different exposure to capitalism. We find that East Germans participated immediately in unfamiliar risky securities, at rates comparable to West Germans of similar characteristics. They phased out disproportionate participation in previously familiar assets as familiarity with capitalist products grew. They were more likely to use consumer debt, partly to catch up with richer new peers. We find no signs of abrupt participation drops that could suggest mistakes or regret related to lack of familiarity.
Does austerity pay off?
(2014)
Policy makers often implement austerity measures when the sustainability of public finances is in doubt and, hence, sovereign yield spreads are high. Is austerity successful in bringing about a reduction in yield spreads? We employ a new panel data set which contains sovereign yield spreads for 31 emerging and advanced economies and estimate the effects of cuts of government consumption on yield spreads and economic activity. The conditions under which austerity takes place are crucial. During times of fiscal stress, spreads rise in response to the spending cuts, at least in the short-run. In contrast, austerity pays off, if conditions are more benign.
The following list includes all traceable films of at least 30 minutes length, which explicitly address the current financial, economic and debt crisis as a main topic and have been available in English or German via European cinemas, television stations, or the internet. This includes dubbed or subtitled versions of films produced in other languages. The film descriptions mostly come from the films’ or television stations’ websites or other marketing material, so they are not necessarily objective (although often informative).
The list is based on an extensive internet search but nevertheless will probably be incomplete and sometimes imprecise. For instance, there is virtually no information about how often the cinema films have actually been shown in theaters; many of them may have been shown just a few times. There are lots of interesting shorter films like The Financial Crisis (Session I–V) (Denmark 2009, Superflex) or RSA Animate: Crises of Capitalism (GB 2010, RSA/David Harvey). Those short films are not listed here, but often they can be easily found and watched online.
The first cultural influences come out in Dobruja together with the appearance of the first German colonists, beginning from 1840 till 1891. The colonization process develops itself in three stages and colonies in places like Tulcea, Malcoci, Almagea, Ciucurova, Cogealac, Tariverde, M. Kogălniceanu and others set up as a result. The German population has created an original culture, an ethnic and spiritual communication being deeply set up, but at the same time a communication struck by the specific conditions imposed by the history of this south-eastern European area. On the other side, the Turkish invasion of Dobruja started earlier, in 1388, when it was actually defeated by Mircea cel Bătrân. In 1393 the Turks succeeded in taking Dobruja and Silistra, but in 1404 Micea cel Bătrân re-conquered the greatest part of these regions. Many Turkish and Tartars moved into Dobruja during the long period of Ottoman rule. The 19th century ethnographic maps show a mainly Turkish population in the area of modern day Dobruja, Tartars and Turks in the southern part of Dobruja and Romanians dominating the north of Dobruja. The paper aims at presenting aspects regarding these two different identities and cultures which are to be found in Dobruja, as well as their integration process within the Romanian Dobrujan modern society.
Establishing coherent identity patterns for literary characters in novels is a difficult task. In this respect, we assume that readers rely on pre-stored cultural models in order to construct mental models of the text content, including character identity. By significantly extending the approach by Van Dijk and Kintsch and going beyond the related accounts of Schneider and of Culpeper, we aim to clarify the constitutive role of conceptual metaphor as proposed by Lakoff et al. in processes of literary identity construction. The analysis of a corpus of three contemporary novels supports our claim that conceptual metaphors and the mapping of domains involved interact with cultural models and connect text phenomena to such prior knowledge structures. On this basis, we provide an integrated model of literary identity construction which acknowledges the constitutive value of conceptual metaphors in literary identity construction.
The Feldbach district is situated near the town of Feldbach in the southeastern province of Styria, Austria. Since 2007, a climate observation network of 151 climate stations within an area of approximately 20 x 15 km (grid cell 1.4 × 1.4 km) has provided a unique collection of spatial and temporal meteorological data. Examining short-lived ruderal and arable weed communities, we search for correlations and spatial patterns between the community composition and climate data. Do such plant communities respond to temperature differences within an agricultural landscape and on a regional scale? Data of 277 relevés from short-lived weed communities were collected across the investigated area during the summer of 2011. Relevés were assigned to the corresponding climate stations and classified. Average Ellenberg indicator values for temperature were calculated for each relevé and community cluster. Measured temperature data were assigned and correlated with community data by applying linear regression and redundancy analyses (RDA). The classification resulted in six associations; the two most frequently observed associations were divided into subtypes resulting in 13 vegetation clusters that could be analyzed further. A significant relationship could be found only between the clusters of arable weed communities and the average winter temperatures. Site variables explain twice as much variance as measured climate variables; this ratio changes to 50 : 50 when we analyzed only arable field community data. No clear spatial patterns concerning mean annual temperature were visible. However, the Setaria faberi subtype of the Echinochloo-Setarietum and the Sorghum halepense subtype of the Convolvulo-Agropyretum show a tendency toward a temperature-induced spatial pattern, such that both were sensitive to winter temperature. On a regional scale, the occurrence and composition of short-lived ruderal plant communities correlated weakly with climate variables. However, the studied arable weed communities showed a certain tendency to follow small-scale temperature differences, especially those of average winter temperature. We conclude that short-lived weed communities have the potential to be indicators for global warming, but the spatial temperature gradients are not clear enough in our approach to allow the production of better regression models and elucidation of distinct spatial patterns.
Reduction and deletion processes occur regularly in conversational speech. A segment that is affected by such reduction and deletion processes in many Germanic languages (e.g., Dutch, English, German) is /t/. There are similarities concerning the factors that influence the likelihood of final /t/ to get deleted, such as segmental context. However, speakers of different languages differ with respect to the acoustic cues they leave in the speech signal when they delete final /t/. German speakers usually lengthen a preceding /s/ when they delete final /t/. This article investigates to what extent German listeners are able to reconstruct /t/ when they are presented with fragments of words where final /t/ has been deleted. It aims also at investigating whether the strategies that are used by German depend on the length of /s/, and therefore whether listeners are using language-specific cues. Results of a forced-choice segment detection task suggest that listeners are able to reconstruct deleted final /t/ in about 45% of the times. The length of /s/ plays some role in the reconstruction, however, it does not explain the behavior of German listeners completely.
We show how repulsive interactions of deconfined quarks as well as confined hadrons have an influence on the baryon number susceptibilities and the curvature of the chiral pseudo-critical line in effective models of QCD. We discuss implications and constraints for the vector interaction strength from comparisons to lattice QCD and comment on earlier constraints, extracted from the curvature of the transition line of QCD and compact star observables. Our results clearly point to a strong vector repulsion in the hadronic phase and near-zero repulsion in the deconfined phase.
Most simulated micro-founded macro models use solely consumer-demand aggregates in order to estimate deep economy-wide preference parameters, which are useful for policy evaluation. The underlying demand-aggregation properties that this approach requires, should be easy to empirically disprove: since household-consumption choices differ for households with more members, aggregation can be rejected if appropriate data violate an affine equation regarding how much individuals benefit from within-household sharing of goods. We develop a survey method that tests the validity of this equation, without utility-estimation restrictions via models. Surprisingly, in six countries, this equation is not rejected, lending support to using consumer-demand aggregates.
DNA methylation reader MECP2 : cell type- and differentiation stage-specific protein distribution
(2014)
Background: Methyl-CpG binding protein 2 (MECP2) is a protein that specifically binds methylated DNA, thus regulating transcription and chromatin organization. Mutations in the gene have been identified as the principal cause of Rett syndrome, a severe neurological disorder. Although the role of MECP2 has been extensively studied in nervous tissues, still very little is known about its function and cell type specific distribution in other tissues.
Results: Using immunostaining on tissue cryosections, we characterized the distribution of MECP2 in 60 cell types of 16 mouse neuronal and non-neuronal tissues. We show that MECP2 is expressed at a very high level in all retinal neurons except rod photoreceptors. The onset of its expression during retina development coincides with massive synapse formation. In contrast to astroglia, retinal microglial cells lack MECP2, similar to microglia in the brain, cerebellum, and spinal cord. MECP2 is also present in almost all non-neural cell types, with the exception of intestinal epithelial cells, erythropoietic cells, and hair matrix keratinocytes. Our study demonstrates the role of MECP2 as a marker of the differentiated state in all studied cells other than oocytes and spermatogenic cells. MECP2-deficient male (Mecp2−/y) mice show no apparent defects in the morphology and development of the retina. The nuclear architecture of retinal neurons is also unaffected as the degree of chromocenter fusion and the distribution of major histone modifications do not differ between Mecp2−/y and Mecp2wt mice. Surprisingly, the absence of MECP2 is not compensated by other methyl-CpG binding proteins. On the contrary, their mRNA levels were downregulated in Mecp2−/y mice.
Conclusions: MECP2 is almost universally expressed in all studied cell types with few exceptions, including microglia. MECP2 deficiency does not change the nuclear architecture and epigenetic landscape of retinal cells despite the missing compensatory expression of other methyl-CpG binding proteins. Furthermore, retinal development and morphology are also preserved in Mecp2-null mice. Our study reveals the significance of MECP2 function in cell differentiation and sets the basis for future investigations in this direction.
Haloferax volcanii uses extracellular DNA as a source for carbon, nitrogen, and phosphorous. However, it can also grow to a limited extend in the absence of added phosphorous, indicating that it contains an intracellular phosphate storage molecule. As Hfx. volcanii is polyploid, it was investigated whether DNA might be used as storage polymer, in addition to its role as genetic material. It could be verified that during phosphate starvation cells multiply by distributing as well as by degrading their chromosomes. In contrast, the number of ribosomes stayed constant, revealing that ribosomes are distributed to descendant cells, but not degraded. These results suggest that the phosphate of phosphate-containing biomolecules (other than DNA and RNA) originates from that stored in DNA, not in rRNA. Adding phosphate to chromosome depleted cells rapidly restores polyploidy. Quantification of desiccation survival of cells with different ploidy levels showed that under phosphate starvation Hfx. volcanii diminishes genetic advantages of polyploidy in favor of cell multiplication. The consequences of the usage of genomic DNA as phosphate storage polymer are discussed as well as the hypothesis that DNA might have initially evolved in evolution as a storage polymer, and the various genetic benefits evolved later.
Divining the Future of Africa : Healing the Wounds, Restoring Dignity and Fostering Development
(2014)
This book explores the relationship between Africa, the West and China. It notes that while Africa is a continent of diverse cultures, raw materials, human resource, indigenous knowledges, and above all the biggest recipient of foreign aid globally, it continues to lag behind all regions of the world in terms of socio-economic development. The book grapples with the important question on why this has been the case. It provides crucial critical insights on how Africa's situation could be reversed and the tapestry of its socio-economic problems eased. The book draws a link between culture, globalisation and socio-economic development, breaking new grounds in the discourse on development in post-colonial Africa. This is an incisive clarion call to bypass the outlandish claims and sterile discussions on the parodying of Africa by Euro-centric scholars. It is a contribution on the imperative to re-think the future of development in Africa. It makes a compelling argument by self-reliant development processes in which Africans reclaim their voice, independence and autonomy unapologetically. The book provides some grist for the mills of policy makers, institutional planners, practitioners and students of anthropology, political studies, sociology, economic history, local governance, cultural economics, and gender, development, African, heritage and international studies.
Panama is a megadiverse country that together with Costa Rica constitutes Lower Central America (LCA). Western Panama's Cordillera Central accounts for the eastern part of the LCA highlands shared between these countries. The aim of the present study is to compile the most complete and updated picture possible of the taxonomy, diversity, and distribution of reptiles that occur from 500 m asl upwards along the Talamanca and Tabasará ranges. These two continuous mountain ridges account for the western two-thirds of the Cordillera Central between the Costa Rican border and 81°W Including specimens collected four own research travels, I morphologically examined more than 1800 specimens, analyzed 16S and/or COI barcodes of 300 specimens, and performed a thorough search in literature and databases to obtain locality records for specimens and species occurrences. My complete occurrence dataset comprises 14620 georeferenced occurrence records in three quality categories. Conceivable occurrences of species not yet documented from a given area are evaluated on the basis of existing data either as "plausible" or "possible". I provide all datasets which I generated for this study in Appendices. The previously published descriptions of Dactyloa ginaelisae Lotzkat, Hertz, Bienentreu & Köhler 2013, Norops benedikti (Lotzkat, Bienentreu, Hertz & Köhler 2011), Sibon perissostichon Köhler, Lotzkat & Hertz 2010, and Sibon noalamina Lotzkat, Hertz & Köhler 2012 are included in the present work. In the course of integrative taxonomic analyses, I classify 15 genealogical lineages revealed by DNA barcoding within 7 anole species as Deep Conspecific Lineages (DCLs) because they lack consistent morphological differences to their nominal conspecifics. I provisionally classify 18 mitochondrial lineages found within six other anole species as Unconfirmed Genealogical Lineages (UGLs) pending adequate analyses of their morphological variation. I regard the two additional UGLs Celestus sp. and Geophis sp. and the two Confirmed Genealogical Lineages (CGLs) Lepidoblepharis sp. 1 and 2 to represent undescribed species. My taxonomic analyses yield the hitherto most comprehensive survey of the variability exhibited by dozens of reptile species in western Panama. The 16S and/or COI barcodes I provide represent 65 species recognized herein and constitute the first DNA barcode reference library for LCA reptiles. The reptile fauna of Panama comprises 265 species, including the four UGLs and CGLs mentioned above and characterized for the first time in this study, as well as Dendrophidion crybelum Cadle 2012 whose presence in the country I consider plausible. My occurrence dataset reveals that 160 of these species have been documented to occur in my study area. Adding the 20 species whose occurrence therein I consider plausible, I report the total species richness of the Talamanca and Tabasará ranges as comprising 180 species representing 81 genera in 25 families. With 178.8 species per 10 000 km2, the relative species richness of the area is extremely high even in a tropical context. In view of their overall documented distribution, I regard the presence of 27 additional species in my study area as possible. For the 180 species occurring in my study area I provide standardized species accounts that, together with the taxonomic results, for the first time permit the doubtless identification of all 180 species, and illustrate 168 of these with color photographs. Concerning biogeography, my georeferenced dataset yields noteworthy distribution extensions for many species. Moreover, I present the hitherto most comprehensive, detailed, and reproducible assessments of the distribution patterns, historical origins, and conservation as well as of the occurrence among physiographic regions, climatic and altitudinal belts, political subdivisions, and protected areas, for my study area's reptile fauna. With 65 species, more than a third of the fauna is endemic to LCA. Among these, 42 Talamancan highland endemics are restricted to the LCA highlands, in the case of 16 small-scale highland endemics with documented ranges spanning less than 100 km. I assess many of these endemics as endangered. The fact that several of these species do not occur in any protected area renders the establishment of additional conservation areas necessary, especially in the central Serranía de Tabasará. Distributional range boundaries shared among different clades of highland anoles indicate physiographic and climatic barriers that may have effected in situ speciation within these lineages. As the largest study on Panamanian reptile diversity assembled to date, the present dissertation considerably increases our knowledge on the reptiles along the Cordillera Central and beyond, and thus constitutes a solid basis for future studies.
Although it is a generally acknowledged fact that Neo-Latin consists of a set of linguistic varieties, there is a short supply of research into its linguistic diversification, especially in non-literary texts. One of the characteristical text classes within Neo-Latin tradition are canonical visitations, a special type of ecclesiastical administrative texts, produced extensively after the Council of Trent in all parts of Europe that had Roman Catholic hierarchical structures. The present paper analyses the language of three canonical visitations written in 18th century Diocese of Senj and Modruš (Krbava) and tries to recognise linguistic peculiarities that could prove to be distinguishing properties for canonical visitations and similar texts.
Cryophytic steppes in the Minusinskaya intermountain basin containing plant species that are predominantly distributed in the alpine zone such as Androsace dasyphylla, Dryas oxyodonta, Festuca sphagnicola, Kobresia myosuroides, K. filifolia, Minuartia verna, Oxytropis bracteata, Sagina saginoides, Papaver nudicaule, Patrinia sibirica, Pedicularis lasiostachys, Pulsatilla ambigua, Saussurea schanginiana, which are considered remnants of the Pleistocene vegetation. Based on 89 relevés, we classified cryophytic steppes using the Braun-Blanquet method within two phytosociological classes: Central Asian steppes of the Cleistogenetea squarrosae and West Palearctic steppes of the Festuco-Brometea. Three associations (Androsaco dasyphyllae-Caricetum pediformis, Pulsatillo patentis-Caricetum pediformis and Bupleuro multinervi-Helictotrichetum desertori) with three subassociations and three variants were described with respect to their phytosociological affinities and ecology. DCA ordination showed floristic differences between syntaxa, while correlations of DCA axes and floristic and environmental variables detected substrate type and temperature regime as presumably main drivers for vegetation differentiation. Another driver for vegetation differentiation seems to be continentality of the climate. Small scale distribution of cryophytic steppes were mapped using satellite images with resolution of 1.8 m. Cryophytic steppes always occupy only small areas in landscapes, on convex parts of undulated microrelief of mountain slopes and summits characterised by drought in summer and deep soil freezing in winter. These special micro-ecological conditions play an essential role for the existence of alpine flora in the Minusinskaya intermountain basin.
The small libellulid genus Rhodothemis is restricted to Asia and Australia. Two of the four included species were described relatively recently by Lohmann (1984) but much previously documented material was never re-identified and the distribution of species in the Indospecies in the Indo-Australian Archipelago remained poorly known. All material available in the Naturalis Biodiversity Center (RMNH) from the eastern part of the Indo-Australian Archipelago was studied and is here brought on record. Key characters are illustrated and SEM images of the genital ligula are presented.
Observation and tracking of fluorescently labeled molecules and particles in living cells reveals detailed information about intracellular processes on the molecular level. Whereas light microscopic particle observation is usually limited to two-dimensional projections of short trajectory segments, we report here image-based real-time three-dimensional single particle tracking in an active feedback loop with single molecule sensitivity. We tracked particles carrying only 1-3 fluorophores deep inside living tissue with high spatio-temporal resolution. Using this approach, we succeeded to acquire trajectories containing several hundred localizations. We present statistical methods to find significant deviations from random Brownian motion in such trajectories. The analysis allowed us to directly observe transitions in the mobility of ribosomal (r)RNA and Balbiani ring (BR) messenger (m)RNA particles in living Chironomus tentans salivary gland cell nuclei. We found that BR mRNA particles displayed phases of reduced mobility, while rRNA particles showed distinct binding events in and near nucleoli.
Dinteria : Nr. 34, 2014
(2014)
Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) usually presents in middle aged men and shows an indolent clinical behavior. However, up to 30% of the patients present a secondary transformation into aggressive diffuse large B cell lymphoma (DLBCL). The aim of the present study was to characterize morphology and immunophenotype of this kind of DLBCL in detail and compare it with conventional DLBCL.
Methods: Morphology and immunophenotype of 33 cases of NLPHL with simultaneous or sequential transformation into DLBCL were investigated. These cases were compared with 41 de novo DLBCL in Finnish men.
Results: The majority of cases exhibited different immunophenotypes in the NLPHL and the DLBCL components. The immunophenotype of the DLBCL secondary to NLPHL was heterogeneous. However, BCL6, EMA, CD75 and J-chain were usually expressed in both components (≥73% positive). Overall, the NLPHL component was more frequently positive for EMA, CD75 and J-chain than the DLBCL component. In contrast, B cell markers, CD10 and BCL2, were more frequently expressed and were expressed at higher levels in the DLBCL component than in the NLPHL component. In the independent series of de novo DLBCL 4 cases could be identified with a growth pattern and immunophenotype that suggested that they had arisen secondarily from NLPHL.
Conclusions: The morphology and immunophenotype of DLBCL arisen from NLPHL is heterogeneous. Further characterization of the particular molecular features of this subgroup is warranted to be able to better identify these cases among conventional DLBCL.
We document and study international differences in both ownership and holdings of stocks, private businesses, homes, and mortgages among households aged fifty or more in thirteen countries, using new and comparable survey data. We employ counterfactual techniques to decompose observed differences across the Atlantic, within the US, and within Europe into those arising from differences in population characteristics and differences in economic environments. We then correlate the latter differences to country-level indicators. Ownership across the range of the assets considered tends to be more widespread among US households. We document that shortly prior to the current crisis, US households tended to invest larger amounts in stocks and smaller ones in homes, and to have larger mortgages in older age, even controlling for characteristics. This is consistent with the high prevalence of negative equity associated with the current crisis. More generally, we find that differences in household characteristics often play a small role, while differences in economic environments tend to explain most of the observed differences in ownership rates and in amounts held. The latter differences are much more pronounced among European countries than among US regions, suggesting further potential for harmonization of policies and institutions.
The measurement of dielectrons (electron-positron pairs) allows to investigate the properties of strongly interacting matter, in particular the Quark-Gluon Plasma (QGP), which is created in relativistic heavy-ion collisions at the LHC. The evolution of the collision can be probed via dielectrons since electrons do not interact strongly and are created during all stages of the collision. One of the interests in dielectron measurements is motivated by possible modifications of the electromagnetic emission spectrum in the QGP, where pp collisions are used as a medium-free reference. The dielectron spectrum consists of contributions from various processes. In order to estimate contributions of known dielectron sources, simulations of the so-called dielectron cocktail are performed. In this thesis, dielectron cocktails in minimum bias pp collisions at p s = 7 TeV, p–Pb collisions at p sNN = 5.02 TeV and in central (0-10%) and semi-central (20-50%) Pb–Pb collisions at p sNN = 2.76 TeV at the LHC are presented.
We explore the sources of household balance sheet adjustment following the collapse of the housing market in 2006. First, we use microdata from the Federal Reserve Board’s Senior Loan Officer Opinion Survey to document that banks cumulatively tightened consumer lending standards more in counties that experienced a house price boom in the mid-2000s than in non-boom counties. We then use the idea that renters, unlike homeowners, did not experience an adverse wealth shock when the housing market collapsed to examine the relative importance of two explanations for the observed deleveraging and the sluggish pickup in consumption after 2008. First, households may have optimally adjusted to lower wealth by reducing their demand for debt and implicitly, their demand for consumption. Alternatively, banks may have been more reluctant to lend in areas with pronounced real estate declines. Our evidence is consistent with the second explanation. Renters with low risk scores, compared to homeowners in the same markets, reduced their levels of nonmortgage debt and credit card debt more in counties where house prices fell more. The contrast suggests that the observed reductions in aggregate borrowing were more driven by cutbacks in the provision of credit than by a demand-based response to lower housing wealth.
Background: Although childhood sexual and/or physical abuse (CSA/CPA) is known to have severe psychopathological consequences, there is little evidence on psychotherapeutic interventions for adolescents and young adults suffering from post-traumatic stress disorder (PTSD). Equally sparse are data on moderators of treatment response on PTSD-related epigenetic changes, health care costs and loss of productivity, alterations in cognitive processing, and on how successful interventions affect all of these factors. Early treatment may prevent later (co)morbidity. In this paper, we present a study protocol for the evaluation of a newly developed psychotherapeutic manual for PTSD after CSA/CPA in adolescents and young adults – the Developmentally Adapted Cognitive Processing Therapy (D-CPT).
Methods/design: In a multicenter randomized controlled trial (RCT) D-CPT is compared to treatment as usual (TAU). A sample of 90 adolescent outpatients aged 14 to 21 years will be randomized to one of these conditions. Four assessments will be carried out at baseline, at end of treatment, and 3 and 6 months after end of therapy. Each time, patients will be assessed via clinical interviews and a wide range of questionnaires. In addition to PTSD symptoms and comorbidities, we will evaluate moderators of treatment response, epigenetic profiles, direct and indirect costs of this disorder, and neurophysiological processing of threat cues in PTSD and their respective changes in the course of these two treatments (D-CPT and TAU).
Discussion: The study will provide new insights in the understudied field of PTSD in adolescents and young adults. A newly developed intervention will be evaluated in this therapeutically underserved population. Results will provide data on treatment efficacy, direct and indirect treatment costs, as well as on associations of treatment outcome and PTSD intensity both to epigenetic profiles and to the neurobiological processing of threat cues. Besides, they will help to learn more about the psychopathology and possible new objective correlates of PTSD.
Trial registration: Germanctr.de identifier: DRKS00004787.
The use of reporter gene fusions to assess cellular processes such as protein targeting and regulation of transcription or translation is established technology in archaeal, bacterial, and eukaryal genetics. Fluorescent proteins or enzymes resulting in chromogenic substrate turnover, like β -galactosidase, have been particularly useful for microscopic and screening purposes. However, application of such methodology is of limited use for strictly anaerobic organisms due to the requirement of molecular oxygen for chromophore formation or color development. We have developed β -lactamase from Escherichia coli (encoded by bla) in conjunction with the chromogenic substrate nitrocefin into a reporter system usable under anaerobic conditions for the methanogenic archaeon Methanosarcina acetivorans. By using a signal peptide of a putative flagellin from M. acetivorans and different catabolic promoters, we could demonstrate growth substrate-dependent secretion of β -lactamase, facilitating its use in colony screening on agar plates. Furthermore, a series of fusions comprised of a constitutive promoter and sequences encoding variants of the synthetic tetracycline-responsive riboswitch (tc-RS) was created to characterize its influence on translation initiation in M. acetivorans. One tc-RS variant resulted in more than 11-fold tetracycline-dependent regulation of bla expression, which is in the range of regulation by naturally occurring riboswitches. Thus, tc-RS fusions represent the first solely cis-active, that is, factor-independent system for controlled gene expression in Archaea.
The laser-driven acceleration of protons from thin foils irradiated by hollow high-intensity laser beams in the regime of target normal sheath acceleration is reported for the first time. The use of hollow beams aims at reducing the initial emission solid angle of the TNSA source, due to a flattening of the electron sheath at the target rear side. The experiments were conducted at the PHELIX laser facility at the GSI Helmholtzzentrum für Schwerionenforschung GmbH with laser intensities in the range from 10^18 to 10^20 W/cm^2. We observed an average reduction of the half opening angle by (3.07±0.42)° or (13.2±2)% when the targets have a thickness between 12 to 14 μm. In addition, the highest proton energies were achieved with the hollow laser beam in comparison to the typical Gaussian focal spot.