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CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Musik und Dichtung sind spätestens seit dem Hohelied Salomos und den bacchantischen Hymnen an Dionysos engstens verbunden. Der gregorianische Gesang des Mittelalters benutzte die lateinischen Texte der Liturgie, Liedkomponisten seit Schubert nehmen ihre Libretti von literarischen Texten her, und Debussys Prélude à l'après-midi d'un faune setzt eine Bekanntschaft mit Mallarmés Gedicht voraus. Die Form der Sonate unterliegt Thomas Manns 'Tonio Kröger' (1903) sowie auch Hermann Hesses 'Der Steppenwolf' (1927), und andere musikalische Formen werden häufig mit raffinierter Bewusstheit angewendet, wie etwa in Robert Pingets 'Passacaille' (1969), Herbert Rosendorfers 'Deutsche Suite' (1972) oder Anthony Burgess' 'Napoleon Symphony' (1974). Thomas Bernhard in 'Der Untergeher' (1983) sowie französische, englische, und amerikanische Schriftsteller derselben Jahre nahmen Bachs Goldberg Variationen als Grundlage für Thema und/oder Struktur ihrer Romane. Und mehrere Komponisten haben versucht, die Musikstücke, die in Thomas Manns 'Doktor Faustus' (1947) so ausführlich beschrieben werden, zu realisieren. So verwundert es kaum, wenn gewisse Motive, die mit der Musik eng verwoben sind auch in Dichtungen auftauchen.
Drei Wellen der Bach-Begeisterung lassen sich seit Mitte des 20. Jahrhunderts deutlich unterscheiden. In der dritten Welle der Bachbegeisterung, erschienen im Jahr 2000 neben der maßgeblichen Biographie des Musikwissenschaftlers Christoph Wolff auch solche popularisierenden Lebensdarstellungen wie Malte Korffs 'Johann Sebastian Bach' in der Reihe DTVPortraits oder RuthAnn Ridleys Roman 'Bach's Passion' (1999), in der Bachs 'Leidenschaften' - vor allem sexuell und religiös - die Hauptrolle spielen. In 'Evening in the Palace of Reason' (2005) präsentiert James R. Gaines eine faszinierende und gut informierte Doppelbiographie von Bach und Friedrich II., die in der Begegnung der beiden Aufklärungs-Genies 1747 in Potsdam und der Komposition von Bachs Musikalischem Opfer kulminiert. (Bereits 2003 wurde im Schweizer Film 'Mein Name ist Bach' [Regie von Dominique de Rivaz] dieselbe Begegnung unter Betonung des sexuellen Lebens beider Männer dargestellt.) Der große Dirigent John Eliot Gardiner lokalisierte seinen Bach (2013) im Kontext der Familie Bach, seiner Altersgenossen Scarlatti und Händel, sowie der gesellschaftlichen und musikalischen Kultur des Jahrhunderts und diskutierte vor allem seine Vokalwerke mit einer Einsicht, die sich nur nach Jahren der persönlichen Praxis und Erfahrung ergibt.
Die literarischen Werke dieser dritten Welle, die nun genauer betrachtet werden sollen, lassen sich wiederum in drei Gruppen unterteilen, von denen die erste und dritte eine theologische Dimension aufweisen, die sich von der rein strukturellen Verwendung von Bachs Goldberg Variationen wie sie sich in der zweiten Welle finden ließ, differenziert.
Das Licht gilt uns als "das" Signum von Humanität, Aufklärung, Erkenntnis und Fortschritt, aber im Theater "übersehen" wir das Licht meist oder reduzieren seinen Einsatz auf eine technische Dienstleistung, die mit "hoher Kunst" scheinbar nichts zu tun hat. Woher kommt das? Und welche Gründe sprechen dafür, dem Licht im Theater mehr Aufmerksamkeit zu schenken, als es viele Zuschauer, Theaterwissenschaftler und Theaterschaffende derzeit tun? Antworten lassen sich unter anderem bei Michel Foucault, Friedrich Schiller und Adolphe Appia finden.
Using the MAXENT algorithm, we developed risk maps for eight invasive plant species in southern Transylvania, Romania, a region undergoing drastic land-use changes. Our findings show that invasion risk increased with landscape heterogeneity. Roads and agricultural areas were most prone to invasion, whereas forests were least at risk.
Seed production varies from year-to-year in most species. Factors influencing this variation can include pollination and dispersal mechanisms, seed predation and resource availability. Here we examine a long-term (12– year) photographic record of seed cone production for the Australian endemic conifer Wollemia nobilis (Araucariaceae). Coefficient of variation (a commonly used measure of variation in seed production) was low for the two trees analysed, compared with published values for other polycarpic plants. Nevertheless, cone production decreased with increasing spring minimum temperatures (during pollination) and increased with summer total rainfall (during cone initiation). Hence, Wollemia nobilis cone production was correlated with weather, in line with the resource-matching hypothesis. Impacts of variation in cone production on the Wollemia nobilis population are likely to be buffered by the shade-tolerant, slow-growing juvenile life stage of Wollemia nobilis.
The advent of improved experimental and theoretical techniques has brought a lot of attention to the electric dipole (E1) response of atomic nuclei in the last decade. The extensive studies have led to the observation and interpretation of a concentration of E1 strength energetically below the Giant Dipole Resonance in many nuclei. This phenomenon is commonly denoted as Pygmy Dipole Resonance (PDR). This contribution will summarize the most important results obtained using different experimental probes, define the challenges to gain a deeper understanding of the excitations, and discuss the newest experimental developments.
Proton-pumping complex I of the mitochondrial respiratory chain is among the largest and most complex membrane protein complexes. The enzyme contributes substantially to oxidative energy-conversion in eukaryotic cells. Its malfunctions are implicated in many hereditary and degenerative disorders. Here, we report the X-ray structure of mitochondrial complex I at 3.6- 3.9 Å resolution describing in detail the central subunits that execute the bioenergetic function. A continuous axis of basic and acidic residues running centrally through the membrane arm connects the ubiquinone reduction site in the hydrophilic arm to four putative proton-pumping units. The binding position for a substrate analogous inhibitor and blockage of the predicted ubiquinone binding site provide a model for the ‘deactive’ form of the enzyme. The proposed transition into the active form is based on a concerted structural rearrangement at the ubiquinone reduction site rendering support for a two-state stabilization-change mechanism of protonpumping.
We investigate charmonium production in Pb + Pb collisions at LHC beam energy Elab=2.76A TeV at fixed-target experiment (√sNN = 72 GeV). In the frame of a transport approach including cold and hot nuclear matter effects on charmonium evolution, we focus on the antishadowing effect on the nuclear modification factors RAA and rAA for the J/ψ yield and transverse momentum. The yield is more suppressed at less forward rapidity (ylab ≃ 2) than that at very forward rapidity (ylab ≃ 4) due to the shadowing and antishadowing in different rapidity bins.
"Die Strahlen der Sonne vertreiben die Nacht" : Licht und Schatten im (Musik-)Theater der Vormoderne
(2015)
Bis zur Mitte des 18. Jahrhunderts waren Akteure und Zuschauer in einem geschlossenen Theaterraum gleich stark beleuchtet, wenn auch nur mit Kerzen und Öllampen. Erst danach geriet die Bühne – nicht ohne Protest der Besucher – ins Zentrum der Beleuchtung. Auf der Opernbühne führte der Einsatz der Kohlenbogenlampe, auch "Prophetensonne" genannt, im 19. Jahrhundert zu einem radikalen Umbruch: Endlich konnten Übergänge vom Dunkel zum Licht musikalisch und szenisch realisiert werden.
Metamorphosen des Helden : menschliche und nicht-menschliche Akteure in der amerikanischen Literatur
(2015)
Der Beitrag stellt die Frage nach dem Verhältnis von menschlichen und nicht-menschlichen Akteuren in der Klima- und Umweltliteratur in einen größeren literaturgeschichtlichen Zusammenhang. Er zeigt, dass einerseits nicht-menschliche Akteure bereits in klassischen Texten der Literatur eine wichtige Rolle spielen und dass andererseits die Betonung nicht-menschlicher Agenzien in der zeitgenössischen Klima- und Umweltliteratur nicht ohne die Präsenz eines in Sprache, Narration, Figurengestaltung und Leserkommunikation manifesten menschlichen Agens auskommt.
The spider collection of the Zoological Museum of the Iranian Research Institute of Plant Protection was studied during the summer of 2014. A total of 180 specimens, belonging to 25 families, 60 genera and 77 species were documented. Of these, the following nine species could be recorded from Iran for the first time: Alopecosa schmidti (Hahn, 1835), Anyphaena accentuata (Walckenaer, 1802), Crustulina sticta (O. P.-Cambridge, 1861), Enoplognatha mordax (Thorell, 1875), Ero tuberculata (De Geer, 1778), Salticus zebraneus (C. L. Koch, 1837), Pardosa aenigmatica Tongiorgi, 1966, Pardosa nebulosa (Thorell, 1872) and Tmarus piochardi (Simon, 1866). Morphological and geographical data are provided for the newly recorded species. Two species (P. aenigmatica and T. piochardi) are illustrated and a map of localities is given.
Previous study of the setae covering the opisthosoma of ground spiders shows that the morphology of the covering setae is genus-specific. The present study pursues the description of covering setae across the whole Gnaphosidae family using SEM. A detailed morphology of the setae of ground spiders (Araneae, Gnaphosidae) is presented. The six major types of covering setae recognized among gnaphosid spiders are squamose, plumose, lanceolate, pinnate, arborate and sicate setae. Squamose setae are characteristic for Micaria lenzi and Nauhea tapa. Plumose setae are more common in ground spiders and occur in the genera Drassodes, Haplodrassus, Anagraphis, Nodocion, Zelotes and the species Berlandina caspica, Nomisia aussereri, Minosiella intermedia, Sosticus loricatus, Leptodrassus memorialis, Intruda signata, Parasyrisca caucasica, Scopoides catharius, Echemoides tofo, Zimiromus medius, Encoptarthria echemophthalma, Apodrassodes trancas, Apopyllus silvestri, Hemicloea sundevalli, Zelanda erebus, Orodrassus assimilis, Callilepis nocturna and Synaphosus turanicus. The species Matua valida, Anzacia gemmea, Hypodrassodes maoricus, Homoeothele micans and Scotophaeus blackwalli have lanceolate setae. Spiders of the genus Gnaphosa have pinnate setae. Fedotovia uzbekistanica has arborate setae. The species Cesonia bilineata, Herpyllus propinquus, Litopyllus temporarius, Aphantaulax seminigra and Kishidaia conspicua have sicate setae. Some genera, such as Drassodes and Synaphosus, have a combination of different types of setae on their opisthosoma, whereas others, like Eilica sp., Laronius erawan, Urozelotes rusticus, have no covering setae on their opisthosoma at all. This study reveals the existence of different types of covering setae and provides a set of characteristics important for the classification and phylogenetic analysis of Gnaphosidae.
Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.
Methylation of ribose sugars at the 2′-OH group is one of the major chemical modifications in rRNA, and is catalyzed by snoRNA directed C/D box snoRNPs. Previous biochemical and computational analyses of the C/D box snoRNAs have identified and mapped a large number of 2′-OH ribose methylations in rRNAs. In the present study, we systematically analyzed ribose methylations of 18S rRNA in Saccharomyces cerevisiae, using mung bean nuclease protection assay and RP-HPLC. Unexpectedly, we identified a hitherto unknown ribose methylation at position G562 in the helix 18 of 5′ central domain of yeast 18S rRNA. Furthermore, we identified snR40 as being responsible to guide snoRNP complex to catalyze G562 ribose methylation, which makes it only second snoRNA known so far to target three ribose methylation sites: Gm562, Gm1271 in 18S rRNA, and Um898 in 25S rRNA. Our sequence and mutational analysis of snR40 revealed that snR40 uses the same D′ box and methylation guide sequence for both Gm562 and Gm1271 methylation. With the identification of Gm562 and its corresponding snoRNA, complete set of ribose methylations of 18S rRNA and their corresponding snoRNAs have finally been established opening great prospects to understand the physiological function of these modifications.
Protein–protein interactions are at the core of all cellular functions and dynamic alterations in protein interactions regulate cellular signaling. In the last decade, mass spectrometry (MS)-based proteomics has delivered unprecedented insights into human protein interaction networks. Affinity purification-MS (AP-MS) has been extensively employed for focused and high-throughput studies of steady state protein–protein interactions. Future challenges remain in mapping transient protein interactions after cellular perturbations as well as in resolving the spatial organization of protein interaction networks. AP-MS can be combined with quantitative proteomics approaches to determine the relative abundance of purified proteins in different conditions, thereby enabling the identification of transient protein interactions. In addition to affinity purification, methods based on protein co-fractionation have been combined with quantitative MS to map transient protein interactions during cellular signaling. More recently, approaches based on proximity tagging that preserve the spatial dimension of protein interaction networks have been introduced. Here, we provide an overview of MS-based methods for analyzing protein–protein interactions with a focus on approaches that aim to dissect the temporal and spatial aspects of protein interaction networks.
Mechanism of Na+-dependent citrate transport from the structure of an asymmetrical CitS dimer
(2015)
The common human pathogen Salmonella enterica takes up citrate as a nutrient via the sodium symporter SeCitS. Uniquely, our 2.5 Å x-ray structure of the SeCitS dimer shows three different conformations of the active protomer. One protomer is in the outside-facing state. Two are in different inside-facing states. All three states resolve the substrates in their respective binding environments. Together with comprehensive functional studies on reconstituted proteoliposomes, the structures explain the transport mechanism in detail. Our results indicate a six-step process, with a rigid-body 31° rotation of a helix bundle that translocates the bound substrates by 16 Å across the membrane. Similar transport mechanisms may apply to a wide variety of related and unrelated secondary transporters, including important drug targets.
The design of rainwater harvesting based gardens requires considering current climate but also climate change during the lifespan of the facility. The goal of this study is to present an approach for designing garden variants that can be safely supplied with harvested rainwater, taking into account climate change and adaptation measures. In addition, the study presents a methodology to quantify the effects of climate change on rainwater harvesting based gardening. Results of the study may not be accurate due to the assumptions made for climate projections and may need to be further refined. We used a tank flow model and an irrigation water model. Then we established three simple climate scenarios and analyzed the impact of climate change on harvested rain and horticulture production for a semi-arid region in northern Namibia. In the two climate scenarios with decreased precipitation and medium/high temperature increase; adaptation measures are required to avoid substantial decreases in horticulture production. The study found that the most promising adaptation measures to sustain yields and revenues are a more water efficient garden variant and an enlargement of the roof size. The proposed measures can partly or completely compensate the negative impacts of climate change.
Network graphs have become a popular tool to represent complex systems composed of many interacting subunits; especially in neuroscience, network graphs are increasingly used to represent and analyze functional interactions between multiple neural sources. Interactions are often reconstructed using pairwise bivariate analyses, overlooking the multivariate nature of interactions: it is neglected that investigating the effect of one source on a target necessitates to take all other sources as potential nuisance variables into account; also combinations of sources may act jointly on a given target. Bivariate analyses produce networks that may contain spurious interactions, which reduce the interpretability of the network and its graph metrics. A truly multivariate reconstruction, however, is computationally intractable because of the combinatorial explosion in the number of potential interactions. Thus, we have to resort to approximative methods to handle the intractability of multivariate interaction reconstruction, and thereby enable the use of networks in neuroscience. Here, we suggest such an approximative approach in the form of an algorithm that extends fast bivariate interaction reconstruction by identifying potentially spurious interactions post-hoc: the algorithm uses interaction delays reconstructed for directed bivariate interactions to tag potentially spurious edges on the basis of their timing signatures in the context of the surrounding network. Such tagged interactions may then be pruned, which produces a statistically conservative network approximation that is guaranteed to contain non-spurious interactions only. We describe the algorithm and present a reference implementation in MATLAB to test the algorithm’s performance on simulated networks as well as networks derived from magnetoencephalographic data. We discuss the algorithm in relation to other approximative multivariate methods and highlight suitable application scenarios. Our approach is a tractable and data-efficient way of reconstructing approximative networks of multivariate interactions. It is preferable if available data are limited or if fully multivariate approaches are computationally infeasible.
In common with several other autoimmune diseases, autoimmune Addison's disease (AAD) is thought to be caused by a combination of deleterious susceptibility polymorphisms in several genes, together with undefined environmental factors and stochastic events. To date, the strongest genomic association with AAD has been with alleles at the HLA locus, DR3-DQ2 and DR4. The contribution of other genetic variants has been inconsistent. We have studied the association of 16 single-nucleotide polymorphisms (SNPs) within the CD28-CTLA-4-ICOS genomic locus, in a cohort comprising 691 AAD patients of Norwegian and UK origin with matched controls. We have also performed a meta-analysis including 1002 patients from European countries. The G-allele of SNP rs231775 in CTLA-4 is associated with AAD in Norwegian patients (odds ratio (OR)=1.35 (confidence interval (CI) 1.10-1.66), P=0.004), but not in UK patients. The same allele is associated with AAD in the total European population (OR=1.37 (CI 1.13-1.66), P=0.002). A three-marker haplotype, comprising PROMOTER_1661, rs231726 and rs1896286 was found to be associated with AAD in the Norwegian cohort only (OR 2.43 (CI 1.68-3.51), P=0.00013). This study points to the CTLA-4 gene as a susceptibility locus for the development of AAD, and refines its mapping within the wider genomic locus.
Monologic dialogues and dialogue structures in Wedekind's 'Frühlings Erwachen' A drama presents a plot which is constituted through dialogues between the characters. This article therefore attempts to explore several instances of dialogue from Wedekind's 'Frühlings Erwachen' by conversationalanalytical means; such an approach facilitates a clear description of the characters' failures in their interactions. This in turn reveals the specific features of literary dialogues from this period, which are constituted in writing and thus precisely planned; an author not only imitates acts and actors via a play's dialogues, but fundamentally creates and moulds the characters through dialogue.
Im Geflecht der Identitäten : Kulturgeschichtliches, dargestellt am Beispiel von János Bolyai
(2015)
The Transylvanian-born János Bolyai (1802-1860) never ceases to attract the attention of all those interested in the history of science, as he is one of the founders of non-Euclidean geometry. Bolyai also concerns the philosophy researchers, due to a social utopia, which he presents in his works, unpublished during his lifetime. From older and newer documentation, it is known that the Hungarian Bolyai nobility descent also has a German origin, from German Grafs. On the Calvaserului Valley, situated north of the Hârtibaciului Valley, lies the Buia parish, named Bolya by the Hungarians, Bell by the Germans, where the Bolyai family owned an estate and a castle. In this work, the author presents approaches concerning the genealogy of János Bolyai and reports about visits to the places where Bolyai has lived, such as Buia, Domald (Viişoara parrish) and Târgu Mureş.
BACKGROUND: Human SAMHD1 is a triphosphohydrolase that restricts the replication of retroviruses, retroelements and DNA viruses in noncycling cells. While modes of action have been extensively described for human SAMHD1, only little is known about the regulation of SAMHD1 in the mouse. Here, we characterize the antiviral activity of murine SAMHD1 with the help of knockout mice to shed light on the regulation and the mechanism of the SAMHD1 restriction and to validate the SAMHD1 knockout mouse model for the use in future infectivity studies.
RESULTS: We found that endogenous mouse SAMHD1 restricts not only HIV-1 but also MLV reporter virus infection at the level of reverse transcription in primary myeloid cells. Similar to the human protein, the antiviral activity of murine SAMHD1 is regulated through phosphorylation at threonine 603 and is limited to nondividing cells. Comparing the susceptibility to infection with intracellular dNTP levels and SAMHD1 phosphorylation in different cell types shows that both functions are important determinants of the antiviral activity of murine SAMHD1. In contrast, we found the proposed RNase activity of SAMHD1 to be less important and could not detect any effect of mouse or human SAMHD1 on the level of incoming viral RNA.
CONCLUSION: Our findings show that SAMHD1 in the mouse blocks retroviral infection at the level of reverse transcription and is regulated through cell cycle-dependent phosphorylation. We show that the antiviral restriction mediated by murine SAMHD1 is mechanistically similar to what is known for the human protein, making the SAMHD1 knockout mouse model a valuable tool to characterize the influence of SAMHD1 on the replication of different viruses in vivo.
In spite of enormous climatic differences between Burkina Faso and Germany, 20 species belong to the spontaneous flora of both countries, i.e. 1% of the flora of Burkina Faso and 0.15 % of the German flora. All of them are either ruderal and segetal species (16) or water and reed plants (4). All of the 16 ruderals/segetals are therophytes. From a recent point of view, most of the 20 species can be classified as cosmopolitan, because they cover three and more floristic zones, and/or at least three climatic zones, and/or are represented in at least three continents. Although Burkina Faso has a semi-arid climate, none of the species can be called a sclero- or xerophyte. Therefore, in Burkina Faso, all are more or less bound to habitats at least temporarily flooded or to humid soils. In Germany, however, the concerned ruderals, with one exception, are indicators of medium dry or dry habitats.
The demography of the alpine pioneer species Saxifraga aizoides was investigated along a successional gradient at the Rotmoos glacier foreland (2,330–2,450 m a.s.l., Obergurgl, Ötztal, Austria) from recently deglaciated areas to advanced successional stages. A basic hypothesis of our study was that fecundity might play an essential role for population growth rate on the youngest site and become of minor importance at advanced successional stages. A matrix modelling approach was performed to calculate the main demographic parameters on 6, 33, and 81 year old moraines. Our results partly confirmed the prediction of the larger role of fecundity on the youngest sites. Here, seedling mortality was lower compared to the older sites, and the reproductive success was significantly higher. All in all, Saxifraga aizoides mainly follows a "persistence strategy" from the beginning, characterized by the fact that large individuals did not undergo mortality at the recently deglaciated site. However, in the long term a population decline will occur due to plant age and changes of environmental conditions along the successional gradient.
The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors, the activity of Nrf2 is inhibited by its interaction with the Keap1 (kelch-like ECH-associated protein 1). Here, we describe (3S)-1-[4-[(2,3,5,6-tetramethylphenyl) sulfonylamino]-1-naphthyl]pyrrolidine-3-carboxylic acid (RA839), a small molecule that binds noncovalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of ∼6 μm, as demonstrated by x-ray co-crystallization and isothermal titration calorimetry. Whole genome DNA arrays showed that at 10 μm RA839 significantly regulated 105 probe sets in bone marrow-derived macrophages. Canonical pathway mapping of these probe sets revealed an activation of pathways linked with Nrf2 signaling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knock-out macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid methyl ester (CDDO-Me), RA839 prevented the induction of both inducible nitric-oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice, RA839 acutely induced Nrf2 target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2.
Im alltäglichen Gespräch lässt sich beobachten, dass bei vielen in der Bundesrepublik aufgewachsenen Personen die Kinderbücher Astrid Lindgrens einen hohen Stellenwert und einen starken Einfluss auf Lebensvorstellungen und Werte des zwischenmenschlichen Miteinanders haben. Wenn die eigene Lebenswelt - wie etwa bestimmte Situationen, Lebensumstände, zwischenmenschliche Beziehungen, die äußere Umwelt, das Lebensgefühl - als besonders beglückend, ja geradezu als ideal empfunden werden, ziehen viele Menschen Parallelen zu den in den Texten Astrid Lindgrens modellierten Lebenswelten. Umgekehrt wird auch versucht, die eigene Lebenswelt nach dem Muster dieser Textwelten zu gestalten, um das Leben so schön, harmonisch und beglückend zu gestalten, wie es die Figuren in den Texten vorleben. Da Texte, die einen solch prägenden Eindruck auf uns ausüben und einen so hohen Stellenwert für die eigenen Lebensvorstellungen und die Lebensgestaltung haben, in der Regel auch an die Nachkommen weitergegeben werden, werden die in den Büchern modellierten Lebensvorstellungen und Werte häufig über mehrere Generationen hinweg tradiert und erhalten einen wichtigen identitätsstabilisierenden Platz im kollektiven Gedächtnis. So können bestimmte Welt-, Lebens- und Wertkonstrukte innerhalb einer Gesellschaft über einen längeren Zeitraum Bestand haben und ein fester Teil des gesellschaftlichen Diskurses werden. Ausgehend von diesen Beobachtungen und Hypothesen scheint es lohnend zu sein, folgende Fragen zu stellen: 1. Lässt sich die eingangs formulierte Alltagsbeobachtung von der Wichtigkeit der Bücher Astrid Lindgrens für die Lebensvorstellungen vieler Deutscher auch durch eine umfassende Untersuchung, also durch konkretes Zahlenmaterial, bestätigen? Oder allgemeiner gefragt: Gibt es Bücher, in denen viele Menschen eine ideale Lebenswelt wiederfinden? 2. Falls es wirklich eines oder mehrere solcher Bücher gibt: Wie genau sieht eine solche ideale Lebenswelt für uns aus? Um diese Fragen zu beantworten, wende ich eine Untersuchungsmethode an, die aus drei Schritten besteht: erstens einer quantitativen Befragung zur Ermittlung eines Textkorpus; zweitens einer literaturwissenschaftlichen Analyse der so ermittelten Texte zur Untersuchung der Rezeptionsangebote dieser Texte; drittens Leitfadeninterviews, um herauszuarbeiten, welche der Textangebote tatsächlich von den Rezipienten aktualisiert werden.
1896, kurz nach dem Tod Paul Verlaines, veröffentlicht der tschechische Künstler Karel Hlaváček seinen Gedichtband 'Pozdě k ránu' ('Spät, gegen Morgen'). Hlaváček wirkt im Kreis Arnošt Procházkas und Jiři Karásek ze Lvovices, Begründer und Herausgeber der Literaturzeitschrift 'Moderní Revue', die mit ihrer dezidiert europäischen Ausrichtung ein Gegengewicht zum nationalistisch-patriotischen Literaturbetrieb in Prag um 1900 bildet. Durch seine Verbindungen zum eher national konservativ orientierten Sokol ist das Verhältnis zu Arnošt Procházka zeitweilig angespannt, wenngleich die Missstimmung weniger konträren politischen Überzeugungen der beiden Männer als den divergierenden Attitüden von 'Moderní Revue' und Sokol geschuldet ist. Seit der Gründung der Zeitschrift 1894 entwirft der junge Hlaváček mehrere Cover für die 'Revue' und ist vorrangig an der Illustration des Blattes beteiligt. Das Oeuvre des mit 23 Jahren früh an Tuberkulose verstorbenen Tschechen ist überschaubar: neben Literaturkritiken und kürzeren Essays und den genannten Gedichtbänden sind 'Mstíva kantiléna' ('Die Rache der Kantilene') und die posthum veröffentlichen 'Žalmy' ('Psalme') seine einzigen Werke. In 'Pozdě k ránu' findet sich das Prosagedicht 'Subtilnost smutku', das nicht nur in einzigartiger Weise eine Auseinandersetzung der in Westeuropa beliebten Topoi und Schreibverfahren der Décadence darstellt, sondern darüber hinaus als kritischer Kommentar zum intellektuellen Milieu im Prag des ausgehenden 19. Jahrhunderts betrachtet werden kann. Der Wahnsinn fungiert in diesem Text im gleichen Maße als komplexe Metapher wie als strukturierendes Leitmotiv und stellt einen Knotenpunkt der verschiedenen Disziplinen, in denen der Begriff "Décadence" im Fin de siècle ungeheure Popularität erlangt, dar. Wenn der Kritiker Herben mit seiner polemischen Kritik versucht, Hlaváček als geisteskrank zu diskreditieren, so verfehlt er seine Absicht dergestalt, dass er nicht nur die Antihaltung des Künstlers befeuert, sondern er identifiziert darüberhinaus das Element, welches sich als Schlüssel zur Dechiffrierung der Stellung von 'Subtilnost smutku' in einem europäischen Rahmen erweisen soll.
The article is a scholary review of the Stefan Kühtz's handbook „Wissenschaftlich formulieren. Tipps und Textbausteine für Studium und Schule” (Scientific express. Tip and text block for studies and school). The book contains the information about, how to write a scientific paper and many of examples of right and wrong sentences. Such tips can be useful not only for students of German as a foreign language, but also for native speakers of german language.
An accurate quantification of low viremic HCV RNA plasma samples has gained importance since the approval of direct acting antivirals and since only one single measurement predicts the necessity of a prolonged or shortened therapy. As reported previously, HCV quantification assays such as Abbott RealTime HCV and Roche COBAS AmpliPrep/COBAS TaqMan HCV version 2 (CTM v2) may vary in sensitivity and precision particularly in low-level viremia. Importantly, substantial variations were previously demonstrated between some of these assays compared to the Roche High Pure System/COBAS TaqMan assay (HPS) reference assay, which was used to establish the clinical decision points in clinical studies. In this study, the reproducibility of assay performances across several laboratories was assessed by analysing quantification results generated by six independent laboratories (3× RealTime, 3× CTM v2) in comparison with one HPS reference laboratory. The 4th WHO Standard was diluted to 100, 25 and 10 IU/ml, and aliquots were tested in triplicates in 5 independent runs by each assay in the different laboratories to assess assay precision and detection rates. In a second approach, 2 clinical samples (GT 1a & GT 1b) were diluted to 100 and 25 IU/ml and tested as described above. While the result range for WHO 100 IU/ml replicates across all laboratories was similar in this analysis, the CVs of each laboratory ranged from 19.3 to 25.6 % for RealTime laboratories and were lower than CVs of CTM v2 laboratories with a range of 26.1–47.3 %, respectively, and also in comparison with the CV of the HPS reference laboratory (34.9 %). At WHO standard dilution of 25 IU/ml, 24 replicates were quantified by RealTime compared to 8 replicates with CTM v2. Results of clinical samples again revealed a higher variation of CTM v2 results as compared to RealTime values. (CVs at 100 IU/ml: RealTime: 13.1–21.0 % and CTM v2: 15.0–32.3 %; CVs at 25 IU/ml: RealTime 17.6–34.9 % and CTM v2 28.2–54.9 %). These findings confirm the superior precision of RealTime versus CTM v2 at low-level viremia even across different laboratories including the new clinical decision point at 25 IU/ml. A highly precise monitoring of HCV viral load during therapy will remain crucial for patient management with regard to futility rules, therapy efficacy and SVR.
Im Jahr 2013 erhielten wir Kenntnis von zwei unabhängig voneinander erworbenen gestempelten Silberbarren, deren genaue Herkunft unbekannt ist, die jedoch aus dem südöstlichen Europa stammen sollen, was durchaus plausibel erscheint. Beide Barren wurden von uns 2014 in einer eigenen kleinen, von der Degussa Goldhandel GmbH (München) herausgegebenen Schrift veröffentlicht.
Background: SNPs near the interferon lambda (IFNL) 3 gene are predictors for sustained virological response (SVR) in patients with chronic hepatitis C genotype (GT) 1. In addition, a dinucleotide frame shift in ss469415590 was described, which generates IFNL4. In this study, we compared the role of IFNL4 variants with IFNL3-(rs12979860) and IFNL3-(rs8099917) on response to pegylated (PEG)-IFN and Ribavirin (RBV) in patients with chronic hepatitis C GT2/3.
Methods: We recruited 1006 patients with chronic hepatitis C and GT2/3 in a large German registry. A treatment with PEG-IFN and Ribavirin was started by 959 patients. We performed genotyping of IFNL3 (rs12979860, n = 726; rs8099917, n = 687) and of IFNL4 (ss469415590; n = 631).
Results: Both preferable IFNL3 genotypes were associated with RVR (both p<0.0001) rather than with SVR (rs12979860: p = 0.251; rs8099917: p = 0.447). Only RVR was linked to SVR in univariate and multivariate analyzes (both p<0.001). Concordance of genotyping in patients with available serum samples and EDTA blood samples (n = 259) was more than 96% for both IFNL3 SNPs. IFNL3-(rs12979860) correlated with IFNL4: 99.2% of patients with IFNL3-(rs12979860)-CC were IFNL4-(ss469415590)-TT/TT. IFNL3-(rs12979860)-CT was linked with IFNL4-(ss469415590)-TT/ΔG (98.0%) and IFNL3-(rs12979860)-TT was associated with IFNL4-(ss469415590)-ΔG/ΔG (97.6%).
Conclusion: IFNL3 genotyping from serum was highly efficient and can be used as an alternative if EDTA whole blood is not available. In Caucasian GT2/3 patients genotyping for INFL4-(ss469415590) does not lead to additional information for the decision-making process. Importantly, IFNL3 SNPs were not associated with SVR but with RVR. Even in the era of new direct acting antiviral (DAA) therapies, IFNL3 testing may therefore still be considered for naïve GT2/3 patients to decide if dual Peg-IFN/RBV therapy is an option in resource limited regions.
In many neural systems anatomical motifs are present repeatedly, but despite their structural similarity they can serve very different tasks. A prime example for such a motif is the canonical microcircuit of six-layered neo-cortex, which is repeated across cortical areas, and is involved in a number of different tasks (e.g. sensory, cognitive, or motor tasks). This observation has spawned interest in finding a common underlying principle, a ‘goal function’, of information processing implemented in this structure. By definition such a goal function, if universal, cannot be cast in processing-domain specific language (e.g. ‘edge filtering’, ‘working memory’). Thus, to formulate such a principle, we have to use a domain-independent framework. Information theory offers such a framework. However, while the classical framework of information theory focuses on the relation between one input and one output (Shannon’s mutual information), we argue that neural information processing crucially depends on the combination of multiple inputs to create the output of a processor. To account for this, we use a very recent extension of Shannon Information theory, called partial information decomposition (PID). PID allows to quantify the information that several inputs provide individually (unique information), redundantly (shared information) or only jointly (synergistic information) about the output. First, we review the framework of PID. Then we apply it to reevaluate and analyze several earlier proposals of information theoretic neural goal functions (predictive coding, infomax and coherent infomax, efficient coding). We find that PID allows to compare these goal functions in a common framework, and also provides a versatile approach to design new goal functions from first principles. Building on this, we design and analyze a novel goal function, called ‘coding with synergy’, which builds on combining external input and prior knowledge in a synergistic manner. We suggest that this novel goal function may be highly useful in neural information processing.
Inspiration for artificial biologically inspired computing is often drawn from neural systems. This article shows how to analyze neural systems using information theory with the aim of obtaining constraints that help to identify the algorithms run by neural systems and the information they represent. Algorithms and representations identified this way may then guide the design of biologically inspired computing systems. The material covered includes the necessary introduction to information theory and to the estimation of information-theoretic quantities from neural recordings. We then show how to analyze the information encoded in a system about its environment, and also discuss recent methodological developments on the question of how much information each agent carries about the environment either uniquely or redundantly or synergistically together with others. Last, we introduce the framework of local information dynamics, where information processing is partitioned into component processes of information storage, transfer, and modification – locally in space and time. We close by discussing example applications of these measures to neural data and other complex systems.
Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice-active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice-active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice-active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty, the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time-dependent approach based on a contact angle distribution (Niedermeier et al., 2014) and a modification of the parameterization presented in Hartmann et al. (2013) representing a time-independent approach. The agreement between these and the measured data were good; i.e., they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
A series of photon scattering experiments has been performed on the double-beta decay partners 76Ge and 76Se, in order to investigate their dipole response up to the neutron separation threshold. Gamma-ray beams from bremsstrahlung at the S-DALINAC and from Compton-backscattering at HIGS have been used to measure absolute cross sections and parities of dipole excited states, respectively. The HIGS data allows for indirect measurement of averaged branching ratios, which leads to significant corrections in the observed excitation cross sections. Results are compared to statistical calculations, to test photon strength functions and the Axel-Brink hypothesis.
Evidence for hydrodynamical flow in AA or in pA collisons is to a large extent obtained from the observation of identified hadrons, such as pions, kaons, and protons. But much more information in particular about the late stage can be obtained by also considering unstable particles, which decay during the lifetime of the expanding hadronic matter. We therefore started to use EPOS3, a unified approach for pp, pA, and AA scattering, to investigate the production of stable and unstable particles.
WHILE CLOUD MARKETS PROMISE UNLIMITED RESOURCE SUPPLIES, INDIVIDUAL PROVIDERS MIGHT BE UNABLE TO OFFER SUFFICIENT PHYSICAL CAPACITY TO SERVE LARGE CUSTOMERS. A SOLUTION IS TO FORM CLOUD COLLABORATIONS, IN WHICH MULTIPLE CLOUD PROVIDERS UNITE FORCES IN ORDER TO CONJOINTLY OFFER CAPACITIES WITHIN CLOUD MARKETS. QUALITY OF SERVICE (QOS) AND SECURITY ASPECTS ARE THE PRIMARY CONSIDERATIONS IN BUILDING SUCH COLLABORATIONS. THIS RESEARCH REPORT PRESENTS A CORRESPONDING OPTIMIZATION APPROACH FOR THE SELECTION OF COLLABORATIVE CLOUD PROVIDERS UNDER CONSIDERATION OF FULFILLMENT OF CLOUD USERS’ QOS AND SECURITY REQUIREMENTS.
O presente artigo parte da compreensão de que os processos de ensino-aprendizagem (no exemplo em questão, o ensino de Alemão como Língua Estrangeira), bem como o andamento de uma aula, são guiados tanto por fatores objetivos (métodos, abordagens, exercícios e testes passíveis de mensuração), quanto por subjetivos. Ao contrário da Didática, que privilegia um viés objetivo, fatos como interferências pessoais, sobretudo voltadas à figura do mestre, influenciam determinantemente a aprendizagem, a ponto de gerar bloqueios e mobilizar os sentimentos dos aprendizes. Tais aspectos podem ser explicados pelo conceito Freudiano de Transferência, nascido na clínica psicanalítica. Outro conceito psicanalítico relevante é a Sublimação, um dos destinos produtivos e socialmente aceitos da Pulsão. Dessa forma, o ensino e a aprendizagem configuram-se como atividades sublimatórias por excelência e que, por isso, de acordo com a visão desenvolvida nesse artigo, devem ser estimuladas pelo mestre, objetivando uma aprendizagem mais consciente e crítica, em sintonia com os desafios educativos do século XXI. Além de "psicanalisar" e desconstruir o processo pedagógico, o artigo situa-se na concepção de uma sala de aula dialógica, com mestres que aprendem e que se constituem a partir da linguagem e do confronto com a alteridade.
Myxomycetes (slime moulds) of arid to semi-arid areas of northwest New South Wales, Australia
(2015)
Myxomycetes (plasmodial slime moulds) were studied along an east-west traverse extending across the arid and semi-arid zones in northwest New South Wales bounded by Lake Cargelligo (400 mm annual rainfall), Bourke (400 mm annual rainfall), Tibooburra (200 mm annual rainfall) and Menindee (250 mm annual rainfall). Samples of tree bark were collected from a range of trees, and subsequently myxomycetes were obtained in the laboratory with the use of the moist culture method. A total of 43 species were recognized. The assemblages of myxomycetes recorded did not change significantly across these climate zones, and, for samples with a reasonable number of species present, there was little difference in diversity due to tree-bark type. The assemblage of species present along this traverse is similar to arid and semi-arid zone tree bark assemblages elsewhere in Australia, which is consistent with the occurrence of one assemblage throughout.
About half of this assemblage consists of widely distributed species likely to be recorded anywhere in the world (cosmopolitan), although these species are found in relatively few samples. The other half of the assemblage is made up of species with a more restricted distribution (generally found in one region of the world or relatively rare worldwide); these species were found in most samples. These restricted distribution species have centres of distribution at a similar latitude and climate in the northern hemisphere.
The assemblage of species associated with bark in the higher rainfall areas of Australia has some of the species of the arid and semi-arid zones; it has most of the widely distributed species and very few of the restricted distribution species. The boundary zone between the two assemblages of species is likely to be near the outer margin of the semiarid zone.
Objectives: Previous studies investigating speech perception in noise have typically been conducted with static masker positions. The aim of this study was to investigate the effect of spatial separation of source and masker (spatial release from masking, SRM) in a moving masker setup and to evaluate the impact of adaptive beamforming in comparison with fixed directional microphones in cochlear implant (CI) users.
Design: Speech reception thresholds (SRT) were measured in S0N0 and in a moving masker setup (S0Nmove) in 12 normal hearing participants and 14 CI users (7 subjects bilateral, 7 bimodal with a hearing aid in the contralateral ear). Speech processor settings were a moderately directional microphone, a fixed beamformer, or an adaptive beamformer. The moving noise source was generated by means of wave field synthesis and was smoothly moved in a shape of a half-circle from one ear to the contralateral ear. Noise was presented in either of two conditions: continuous or modulated.
Results: SRTs in the S0Nmove setup were significantly improved compared to the S0N0 setup for both the normal hearing control group and the bilateral group in continuous noise, and for the control group in modulated noise. There was no effect of subject group. A significant effect of directional sensitivity was found in the S0Nmove setup. In the bilateral group, the adaptive beamformer achieved lower SRTs than the fixed beamformer setting. Adaptive beamforming improved SRT in both CI user groups substantially by about 3 dB (bimodal group) and 8 dB (bilateral group) depending on masker type.
Conclusions: CI users showed SRM that was comparable to normal hearing subjects. In listening situations of everyday life with spatial separation of source and masker, directional microphones significantly improved speech perception with individual improvements of up to 15 dB SNR. Users of bilateral speech processors with both directional microphones obtained the highest benefit.
The neutron capture cross section of the s-process branch nucleus 63Ni affects the abundances of other nuclei in its region, especially 63Cu and 64Zn. In order to determine the energy-dependent neutron capture cross section in the astrophysical energy region, an experiment at the Los Alamos National Laboratory has been performed using the calorimetric 4πBaF2 array DANCE. The (n,γ) cross section of 63Ni has been determined relative to the well-known 197Au standard with uncertainties below 15%. Various 63Ni resonances have been identified based on the Q value. Furthermore, the s-process sensitivity of the new values was analyzed with the new network calculation tool NETZ.
Friede den Hütten! Krieg den Palästen!
Im Jahre 1834 siehet es aus, als würde die Bibel Lügen gestraft. Es sieht aus, als hätte Gott die Bauern und Handwerker am fünften Tage und die Fürsten und Vornehmen am sechsten gemacht, und als hätte der Herr zu diesen gesagt: 'Herrschet über alles Getier, das auf Erden kriecht', und hätte die Bauern und Bürger zumGewürm gezählt. Das Leben der Vornehmen ist ein langer Sonntag: sie wohnen inschönen Häusern, sie tragen zierliche Kleider, sie haben feiste Gesichter und redeneine eigne Sprache; das Volk aber liegt vor ihnen wie Dünger auf dem Acker. DerBauer geht hinter dem Pflug, der Vornehme aber geht hinter ihm und dem Pflug und treibt ihn mit den Ochsen am Pflug, er nimmt das Korn und läßt ihm die Stoppeln. Das Leben des Bauern ist ein langer Werktag; Fremde verzehren seine Äcker vor seinen Augen, sein Leib ist eine Schwiele, sein Schweiß ist das Salz auf dem Tische des Vornehmen.
Mit dieser rhetorischen Fanfare beginnt der Hessische Landbote, jene politische Flugschrift, die Georg Büchner 1834, noch vor seinen eigentlich literarischen Werken, veröffentlichte. Es ist der Text in Büchners Werk, in dem die biblischen Bezüge am deutlichsten sind, wie in der zitierten Passage nicht nur die explizite Erwähnung der Bibel im ersten Satz und die deutliche Anspielung auf Jesaja 1.7 "Fremde verzehren eure Acker vor euren Augen" zeigt. Auch der gesamte Tonfall, jene Mischung von Vehemenz und Anschaulichkeit, die den Landboten insgesamt auszeichnet, ist biblisch geprägt. Allerdings wissen wir nicht einmal sicher, ob dieser zitierte Anfang von Büchner stammt, denn der Landbote hat zwei Autoren: Georg Büchner und Friedrich Ludwig Weidig, der einen nicht überlieferten Entwurf von Büchner überarbeitet und ergänzt hat, so dass am Ende kaum zu sagen ist, wer hier was geschrieben hat.
Gallbladder cancer (GBC) is a highly malignant tumor characterized by a poor response to chemotherapy and radiotherapy. We evaluated the in vitro and in vivo antitumor efficacy of mTOR inhibitors, rapamycin and WYE-354. In vitro assays showed WYE-354 significantly reduced cell viability, migration and invasion and phospho-P70S6K expression in GBC cells. Mice harboring subcutaneous gallbladder tumors, treated with WYE-354 or rapamycin, exhibited a significant reduction in tumor mass. A short-term treatment with a higher dose of WYE-354 decreased the tumor size by 68.6% and 52.4%, in mice harboring G-415 or TGBC-2TKB tumors, respectively, compared to the control group. By contrast, treatment with a prolonged-low-dose regime of rapamycin almost abrogated tumor growth, exhibiting 92.7% and 97.1% reduction in tumor size, respectively, compared to control mice. These results were accompanied by a greater decrease in the phosphorylation status of P70S6K and a lower cell proliferation Ki67 index, compared to WYE-354 treated mice, suggesting a more effective mTOR pathway inhibition. These findings provide a proof of concept for the use of rapamycin or WYE-354 as potentially good candidates to be studied in clinical trials in GBC patients.
Signal transducers and activators of transcription (Stats) play central roles in the conversion of extracellular signals, e.g., cytokines, hormones and growth factors, into tissue and cell type specific gene expression patterns. In normal cells, their signaling potential is strictly limited in extent and duration. The persistent activation of Stat3 or Stat5 is found in many human tumor cells and contributes to their growth and survival. Stat5 activation plays a pivotal role in nearly all hematological malignancies and occurs downstream of oncogenic kinases, e.g., Bcr-Abl in chronic myeloid leukemias (CML) and Jak2(V617F) in other myeloproliferative diseases (MPD). We defined the mechanisms through which Stat5 affects growth and survival of K562 cells, representative of Bcr-Abl positive CML, and HEL cells, representative for Jak2(V617F) positive acute erythroid leukemia. In our experiments we suppressed the protein expression levels of Stat5a and Stat5b through shRNA mediated downregulation and demonstrated the dependence of cell survival on the presence of Stat5. Alternatively, we interfered with the functional capacities of the Stat5 protein through the interaction with a Stat5 specific peptide ligand. This ligand is a Stat5 specific peptide aptamer construct which comprises a 12mer peptide integrated into a modified thioredoxin scaffold, S5-DBD-PA. The peptide sequence specifically recognizes the DNA binding domain (DBD) of Stat5. Complex formation of S5-DBD-PA with Stat5 causes a strong reduction of P-Stat5 in the nuclear fraction of Bcr-Abl-transformed K562 cells and a suppression of Stat5 target genes. Distinct Stat5 mediated survival mechanisms were detected in K562 and Jak2(V617F)-transformed HEL cells. Stat5 is activated in the nuclear and cytosolic compartments of K562 cells and the S5-DBD-PA inhibitor most likely affects the viability of Bcr-Abl+ K562 cells through the inhibition of canonical Stat5 induced target gene transcription. In HEL cells, Stat5 is predominantly present in the cytoplasm and the survival of the Jak2(V617F)+ HEL cells is impeded through the inhibition of the cytoplasmic functions of Stat5.
"Jedes einzelne Bild nur ein Mosaikstück"? : zur Funktion des Erzählens in Eva Menasses Werken
(2015)
Eva Menasses erzählerisches Werk hat seit dem Erscheinen ihres ersten Romans Vienna (2005) sowohl bei Kritikern als auch beim lesenden Publikum einige Aufmerksamkeit auf sich gezogen. In den vielen, überwiegend positiven Besprechungen ihrer Bücher werden immer wieder deren dichte Atmosphäre, die kunstvolle Komposition, vor allem aber der darin zu findende "scharfe Witz" hervorgehoben, und ihre literarische Qualität wird nur selten in Zweifel gezogen. Angesichts dessen ist es nur wenig verwunderlich, dass auch die Literaturwissenschaft sich bereits für ihre Werke zu interessieren begonnen hat, wenn auch vorwiegend für die spezifischen Identitätsprobleme, die Menasse in Vienna unter den Nachfahren der jüdischen Überlebenden des Holocaust ausmacht. An dieser Schwerpunktsetzung lässt sich insofern auch kaum etwas aussetzen, als Menasse selbst großen Wert auf diese Frage gelegt und nachdrücklich betont hat: "Das einzige für mich wirklich wichtige Thema [in Vienna] ist die Geschichte des 20. Jahrhunderts und die Frage der Identität. Das allein ist der Antrieb gewesen, diesen Roman zu schreiben." Dennoch ist durch die Konzentration auf diese Fragestellung die ästhetische Seite ihrer Bücher bislang weitgehend unbeleuchtet geblieben, obwohl sich dazu in den Texten mehr als genug Reflexionen finden, gerade was die Frage nach der möglichen Leistung, aber auch nach den Grenzen des Erzählens anbelangt. Dies ist umso bedauerlicher, als genau darin der Kern der bislang erschienen Werke zu bestehen scheint, insofern diese Reflexionen nicht nur das Thema der Identität entscheidend zu erhellen vermögen, sondern überhaupt erst sichtbar werden lassen, dass auch die Bücher nach Vienna, trotz ihrer sonst sehr unterschiedlichen Thematik und ästhetischen Anlage, allesamt auf die im ersten Buch bereits aufgeworfenen Probleme bezogen bleiben. Im Folgenden soll deshalb versucht werden, diese Probleme und die Verbindungen zwischen den einzelnen Werken klarer herauszuarbeiten, um so zu einer möglichst deutlichen Anschauung und einer ersten Einordnung von Menasses bisherigem Schaffen zu gelangen.
Background: Second hand smoke (ETS)-associated particulate matter (PM) contributes considerably to indoor air contamination and constitutes a health risk for passive smokers. Easy to measure, PM is a useful parameter to estimate the dosage of ETS that passive smokers are exposed to. Apart from its suitability as a surrogate parameter for ETS-exposure, PM itself affects human morbidity and mortality in a dose-dependent manner. We think that ETS-associated PM should be considered an independent hazard factor, separately from the many other known harmful compounds of ETS. We believe that brand-specific and tobacco-product-specific differences in the release of PM matter and that these differences are of public interest. Methods: To generate ETS of cigarettes and cigarillos as standardized and reproducible as possible, an automatic second hand smoke emitter (AETSE) was developed and placed in a glass chamber. L&M cigarettes ("without additives", "red label", "blue label"), L&M filtered cigarillos ("red") and 3R4F standard research cigarettes (as reference) were smoked automatically according to a self-developed, standardized protocol until the tobacco product was smoked down to 8 mm distance from the tipping paper of the filter. Results: Mean concentration (Cmean) and area under the curve (AUC) in a plot of PM2.5 against time were measured, and compared. CmeanPM2.5 were found to be 518 μg/m3 for 3R4F cigarettes, 576 μg/m3 for L&M "without additives" ("red"), 448 μg/m3 for L&M "blue label", 547 μg/m3 for L&M "red label", and 755 μg/m3 for L&M filtered cigarillos ("red"). AUCPM2.5-values were 208,214 μg/m3·s for 3R4F reference cigarettes, 204,629 μg/m3·s for L&M "without additives" ("red"), 152,718 μg/m3·s for L&M "blue label", 238,098 μg/m3·s for L&M "red label" and 796,909 μg/m3·s for L&M filtered cigarillos ("red"). Conclusion: Considering the large and significant differences in particulate matter emissions between cigarettes and cigarillos, we think that a favorable taxation of cigarillos is not justifiable.
The bug Gyaclavator kohlsi Wappler, Guilbert, Wedmann et Labandeira, gen. et sp. nov., represents a new extinct genus of lace bugs (Insecta: Heteroptera: Tingidae) occurring in latest early Eocene deposits of the Green River Formation, from the southern Piceance Basin of Northwestern Colorado, in North America. Gyaclavator can be placed within the Tingidae with certainty, perhaps it is sistergroup to Cantacaderinae. If it belongs to Cantacaderinae, it is the first fossil record of this group for North America. Gyaclavator has unique, conspicuous antennae bearing a specialized, highly dilated distiflagellomere, likely important for intra- or intersex reproductive competition and attraction. This character parallels similar antennae in leaf-footed bugs (Coreidae), and probably is associated with a behavioral convergence as well.
Der eingetopfte Held : kulturökologische Relektüre des Romans "Ein ungeratener Sohn" von Renate Rasp
(2015)
In dem heute fast vergessenen Roman von Renate Rasp, Ein ungeratener Sohn, wird in der Form einer bitterbösen Satire gezeigt, was Erziehung anrichten kann. Eine bürgerliche Kleinfamilie beschließt, dass aus dem Sohn Kuno ein Baum werden soll. Der Transformationsprozess zur vegetabilen Lebensform durchläuft verschiedene Stadien vom Abhacken der Hände und Verschließen der Sinne bis zum Eintopfen, muss jedoch am Ende scheitern. Die traditionelle Lesart dechiffriert den Text als radikale Kritik am Zusammenhang von Bildung, Erziehung und Herrschaft. Unter kulturökologischer Prämisse gelesen, tritt im Beitrag klar hervor, wie sich der Mensch-Natur-Herrschaftsdiskurs in diesem Roman entfaltet.
Low-level-laser therapy (LLLT) is an effective complementary treatment, especially for anti-inflammation and wound healing in which dermis or mucus mast cells (MCs) are involved. In periphery, MCs crosstalk with neurons via purinergic signals and participate in various physiological and pathophysiological processes. Whether extracellular ATP, an important purine in purinergic signaling, of MCs and neurons could be modulated by irradiation remains unknown. In this study, effects of red-laser irradiation on extracellular ATP content of MCs and dorsal root ganglia (DRG) neurons were investigated and underlying mechanisms were explored in vitro. Our results show that irradiation led to elevation of extracellular ATP level in the human mast cell line HMC-1 in a dose-dependent manner, which was accompanied by elevation of intracellular ATP content, an indicator for ATP synthesis, together with [Ca2+]i elevation, a trigger signal for exocytotic ATP release. In contrast to MCs, irradiation attenuated the extracellular ATP content of neurons, which could be abolished by ARL 67156, a nonspecific ecto-ATPases inhibitor. Our results suggest that irradiation potentiates extracellular ATP of MCs by promoting ATP synthesis and release and attenuates extracellular ATP of neurons by upregulating ecto-ATPase activity. The opposite responses of these two cell types indicate complex mechanisms underlying LLLT.
Inverted perceptual judgment of nociceptive stimuli at threshold level following inconsistent cues
(2015)
Objective: The perception of pain is susceptible to modulation by psychological and contextual factors. It has been shown that subjects judge noxious stimuli as more painful in a respective suggestive context, which disappears when the modifying context is resolved. However, a context in which subjects judge the painfulness of a nociceptive stimulus in exactly the opposite direction to that of the cues has never been shown so far.
Methods: Nociceptive stimuli (300 ms intranasal gaseous CO2) at the individual pain threshold level were applied after a visual cue announcing the stimulus as either "no pain", merely a "stimulus", or "pain". Among the stimuli at threshold level, other CO2 stimuli that were clearly below or above pain threshold were randomly interspersed. These were announced beforehand in 12 subjects randomly with correct or incorrect cues, i.e., clearly painful or clearly non-painful stimuli were announced equally often as not painful or painful. By contrast, in a subsequent group of another 12 subjects, the stimuli were always announced correctly with respect to the evoked pain.
Results: The random and often incorrect announcement of stimuli clearly below or above pain threshold caused the subjects to rate the stimuli at pain-threshold level in the opposite direction of the cue, i.e., when the stimuli were announced as "pain" significantly more often than as non-painful and vice versa (p < 10-4). By contrast, in the absence of incongruence between announcement and perception of the far-from-threshold stimuli, stimuli at pain threshold were rated in the cued direction.
Conclusions: The present study revealed the induction of associations incongruent with a given message in the perception of pain. We created a context of unreliable cues whereby subjects perceived the stimulus opposite to that suggested by a prior cue, i.e., potentially nociceptive stimuli at pain threshold level that were announced as painful were judged as non-painful and vice versa. These findings are consistent with reported data on the effects of distrust on non-painful cognitive responses.
Die Glühbirne hat ausgedient. Auch Energiesparlampen sind nur eine Übergangslösung. Große Hoffnungen richten sich auf organische Leuchtdioden, zumal man daraus auch großflächige und biegsame Displays und Flachbildschirme herstellen kann. Für eines der größten Probleme, das Ausbleichen der blauen Leuchtstoffe, findet man immer bessere Lösungen. Anwendungen, die heute noch wie Science-Fiction klingen, rücken damit in erreichbare Nähe.
Pflanzen, aber auch einige Bakterien und Archäen verfügen über hocheffiziente Mechanismen, Licht in Energie umzuwandeln. Photovoltaik-Zellen reichen an die Perfektion dieser natürlichen Systeme noch lange nicht heran. Deshalb versuchen Forscher, mit ultraschnellen spektroskopischen Methoden der Natur in die Karten zu schauen und von ihr zu lernen.
Synaptic vesicles (SVs) undergo a cycle of biogenesis and membrane fusion to release transmitter, followed by recycling. How exocytosis and endocytosis are coupled is intensively investigated. We describe an all-optical method for identification of neurotransmission genes that can directly distinguish SV recycling factors in C. elegans, by motoneuron photostimulation and muscular RCaMP Ca2+ imaging. We verified our approach on mutants affecting synaptic transmission. Mutation of genes affecting SV recycling (unc-26 synaptojanin, unc-41 stonin, unc-57 endophilin, itsn-1 intersectin, snt-1 synaptotagmin) showed a distinct ‘signature’ of muscle Ca2+ dynamics, induced by cholinergic motoneuron photostimulation, i.e. faster rise, and earlier decrease of the signal, reflecting increased synaptic fatigue during ongoing photostimulation. To facilitate high throughput, we measured (3–5 times) ~1000 nematodes for each gene. We explored if this method enables RNAi screening for SV recycling genes. Previous screens for synaptic function genes, based on behavioral or pharmacological assays, allowed no distinction of the stage of the SV cycle in which a protein might act. We generated a strain enabling RNAi specifically only in cholinergic neurons, thus resulting in healthier animals and avoiding lethal phenotypes resulting from knockdown elsewhere. RNAi of control genes resulted in Ca2+ measurements that were consistent with results obtained in the respective genomic mutants, albeit to a weaker extent in most cases, and could further be confirmed by opto-electrophysiological measurements for mutants of some of the genes, including synaptojanin. We screened 95 genes that were previously implicated in cholinergic transmission, and several controls. We identified genes that clustered together with known SV recycling genes, exhibiting a similar signature of their Ca2+ dynamics. Five of these genes (C27B7.7, erp-1, inx-8, inx-10, spp-10) were further assessed in respective genomic mutants; however, while all showed electrophysiological phenotypes indicative of reduced cholinergic transmission, no obvious SV recycling phenotypes could be uncovered for these genes.
We compiled an NMR data set consisting of exact nuclear Overhauser enhancement (eNOE) distance limits, residual dipolar couplings (RDCs) and scalar (J) couplings for GB3, which forms one of the largest and most diverse data set for structural characterization of a protein to date. All data have small experimental errors, which are carefully estimated. We use the data in the research article Vogeli et al., 2015, Complementarity and congruence between exact NOEs and traditional NMR probes for spatial decoding of protein dynamics, J. Struct. Biol., 191, 3, 306–317, doi:10.1016/j.jsb.2015.07.008 [1] for cross-validation in multiple-state structural ensemble calculation. We advocate this set to be an ideal test case for molecular dynamics simulations and structure calculations.
Na temelju terenskoga istraživanja u radu se donosi sinkronijski prikaz naglasnih paradigma imenica e-vrste i i-vrste u slivanjskim govorima Slivna Ravnoga, Mihalja, Blaca i Podgradine. Riječ je o govorima koji pripadaju istočnohercegovačkomu dijalektu, slivanjsko-zažapskomu govornom tipu. Utvrdit će se postoje li kolebanja u pojedinoj paradigmi i među paradigmama te čuvanje kračine u d./l./i.
Der 'brave Soldat' Schwejk - antiheroischer Protagonist in Jaroslavs Hašeks berühmtem Roman - beobachtet auf dem Weg zur Front einen vorbeifahrenden Militärzug mit offenen Waggons: Ein Korporal der Deutschmeister 'mit herausfordernd aufgezwirbeltem Schnurrbart' stützt sich wie in einem 'lebendem Bild' quer auf seine sitzende Mannschaft, schmettert voller Inbrunst das Prinz-Eugen-Lied, lehnt sich übermütig hinaus - und fliegt aus der offenen Waggontür, wobei er 'mit aller Kraft im Flug mit dem Bauch auf den Weichenhebel [schlug], auf dem er aufgespießt hängenblieb'. 'Mit Kennermiene' betrachtet Schwejk neugierig den Leichnam: "Der hats schon hinter sich […] hat sich akkurat aufgespießt […], hat die Därme in den Hosen." Das groteske Ende des Offiziers der Deutschmeister, jenes Ritterordens aus dem 12. Jahrhundert, symbolisiert den Untergang des aristokratischen Kriegerstandes - des Inbegriffs menschlicher Souveränität, die in Gestalt verführerischer Husaren noch Romane und Operetten des 19. Jahrhunderts bevölkerte - in den Höllenfeuern des Maschinenkrieges, zu dem Schwejk und seine Kameraden gerade unterwegs sind. Auch sein geliebter Herr, Oberleutnant Lukasch, ein notorischer Verführer, repräsentiert noch jene aristokratische Souveränität, Glanzstück des feudalen Ständestaates: Hoch zu Roß reitet er nicht nur dem Feind entgegen, sondern zugleich seinem Untergang, der sich in den Materialschlachten des großindustriellen Krieges vollzieht.
Was Schwejk fasziniert beobachtet, ist das finale Stadium des Zusammenbruchs der ständischen Ordnung, der patriarchalischen Autorität, der feudalen Tugenden, der symbolischen Repräsentation, der Hierarchie der Gemeinschaften im Versachlichungs- und Entzauberungsprozess der Moderne. Dabei bewegte Literatur und Philosophie des 19. Jahrhunderts vor allem eine Frage: Was geschieht eigentlich, wenn 'der Knecht' (aus Hegels Phänomenologie des Geistes) - das "durch die Arbeit" erwirkte Selbstbewusstsein mit seinem Primat von Selbsterhaltung und instrumenteller Rationalität - zum Herrn wird, mit den souveränen Eigenschaften des untergegangenen Herrn?
CD44v6, a member of the CD44 family of transmembrane glycoproteins is a co-receptor for two receptor tyrosine kinases (RTKs), Met and VEGFR-2 (vascular endothelial growth factor receptor 2). CD44v6 is not only required for the activation of these RTKs but also for signalling. In order to understand the role of CD44v6 in Met and VEGFR-2 activation and signalling we tested whether CD44v6 binds to their ligands, HGF (hepatocyte growth factor) and VEGF (vascular endothelial growth factor), respectively. FACS analysis and cellular ELISA showed binding of HGF and VEGF only to cells expressing CD44v6. Direct binding of CD44v6 to HGF and VEGF was demonstrated in pull-down assays and the binding affinities were determined using MicroScale Thermophoresis, fluorescence correlation spectroscopy and fluorescence anisotropy. The binding affinity of CD44v6 to HGF is in the micromolar range in contrast with the high-affinity binding measured in the case of VEGF and CD44v6, which is in the nanomolar range. These data reveal a heparan sulfate-independent direct binding of CD44v6 to the ligands of Met and VEGFR-2 and suggest different roles of CD44v6 for these RTKs.
Liberal political philosophy has two alternative options in principle: It can either stick to its original theorems such as the harm principle or the separation of law and morals and from here try to prove large parts of present social and political reality as wrong, illegitimate, dangerous etc. The other option is trying to adjust the original theorems to the apparent needs of modern societies, which is what I would prefer in the long run.
Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP
(2015)
Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1(+/-) mice, which are animal correlates of human PRG-1(+/mut) carriers, showed an altered cortical network function and stress-related behavioral changes indicating altered resilience against psychiatric disorders. These could be reversed by modulation of phospholipid signaling via pharmacological inhibition of the LPA-synthesizing molecule autotaxin. In line, EEG recordings in a human population-based cohort revealed an E/I balance shift in monoallelic mutPRG-1 carriers and an impaired sensory gating, which is regarded as an endophenotype of stress-related mental disorders. Intervention into bioactive lipid signaling is thus a promising strategy to interfere with glutamate-dependent symptoms in psychiatric diseases.
Introduction: By producing H2O2, the NADPH oxidase Nox4 is involved in differentiation of mesenchymal cells. Exercise alters the composition of slow and fast twitch fibres in skeletal. Here we hypothesized that Nox4 contributes to exercise-induced adaptation such as changes in muscle metabolism or muscle fibre specification and studied this in wildtype and Nox4-/- mice.
Results: Exercise, as induced by voluntary running in a running wheel or forced running on a treadmill induced a switch from fast twitch to intermediate fibres. However the induced muscle fibre switch was similar between Nox4-/- and wildtype mice. The same held true for exercise-induced expression of PGC1α or AMPK activation. Both are increased in response to exercise, but with no difference was observed between wildtype and Nox4-/- mice.
Conclusion: Thus, exercise-induced muscle fibre switch is Nox4-independent.
The caddisfly subfamily Drusinae BANKS comprises roughly 100 species inhabiting mountain ranges in Europe, Asia Minor and the Caucasus. A 3-gene phylogeny of the subfamily previously identified three major clades that were corroborated by larval morphology and feeding ecologies: scraping grazers, omnivorous shredders and filtering carnivores. Larvae of filtering carnivores exhibit unique head capsule complexities, unknown from other caddisfly larvae. Here we assess the species-level relationships within filtering carnivores, hypothesizing that head capsule complexity is derived from simple shapes observed in the other feeding groups. We summarize the current systematics and taxonomy of the group, clarify the systematic position of Cryptothrix nebulicola, and present a larval key to filtering carnivorous Drusinae. We infer relationships of all known filtering carnivorous Drusinae and 34 additional Drusinae species using Bayesian species tree analysis and concatenated Bayesian phylogenetic analysis of 3805bp of sequence data from six gene regions (mtCOI5-P, mtCOI3-P, 16S mrDNA, CADH, WG, 28S nrDNA), morphological cladistics from 308 characters, and a total evidence analysis. All analyses support monophyly of the three feeding ecology groups but fail to fully resolve internal relationships. Within filtering carnivores, variation in head setation and frontoclypeus structure may be associated with progressive niche adaptation, with less complex species recovered at a basal position. We propose that diversification of complex setation and frontoclypeus shape represents a recent evolutionary development, hypothetically enforcing speciation and niche specificity within filtering carnivorous Drusinae.
Modelling short-term variability in carbon and water exchange in a temperate Scots pine forest
(2015)
The vegetation–atmosphere carbon and water exchange at one particular site can strongly vary from year to year, and understanding this interannual variability in carbon and water exchange (IAVcw) is a critical factor in projecting future ecosystem changes. However, the mechanisms driving this IAVcw are not well understood. We used data on carbon and water fluxes from a multi-year eddy covariance study (1997–2009) in a Dutch Scots pine forest and forced a process-based ecosystem model (Lund–Potsdam–Jena General Ecosystem Simulator; LPJ-GUESS) with local data to, firstly, test whether the model can explain IAVcw and seasonal carbon and water exchange from direct environmental factors only. Initial model runs showed low correlations with estimated annual gross primary productivity (GPP) and annual actual evapotranspiration (AET), while monthly and daily fluxes showed high correlations. The model underestimated GPP and AET during winter and drought events. Secondly, we adapted the temperature inhibition function of photosynthesis to account for the observation that at this particular site, trees continue to assimilate at very low atmospheric temperatures (up to daily averages of −10 °C), resulting in a net carbon sink in winter. While we were able to improve daily and monthly simulations during winter by lowering the modelled minimum temperature threshold for photosynthesis, this did not increase explained IAVcw at the site. Thirdly, we implemented three alternative hypotheses concerning water uptake by plants in order to test which one best corresponds with the data. In particular, we analyse the effects during the 2003 heatwave. These simulations revealed a strong sensitivity of the modelled fluxes during dry and warm conditions, but no single formulation was consistently superior in reproducing the data for all timescales and the overall model–data match for IAVcw could not be improved. Most probably access to deep soil water leads to higher AET and GPP simulated during the heatwave of 2003. We conclude that photosynthesis at lower temperatures than assumed in most models can be important for winter carbon and water fluxes in pine forests. Furthermore, details of the model representations of water uptake, which are often overlooked, need further attention, and deep water access should be treated explicitly.
Modelling short-term variability in carbon and water exchange in a temperate Scots pine forest
(2015)
The vegetation–atmosphere carbon and water exchange at one particular site can strongly vary from year to year, and understanding this interannual variability in carbon and water exchange (IAVcw) is a critical factor in projecting future ecosystem changes. However, the mechanisms driving this IAVcw are not well understood. We used data on carbon and water fluxes from a multi-year eddy covariance study (1997–2009) in a Dutch Scots pine forest and forced a process-based ecosystem model (Lund–Potsdam–Jena General Ecosystem Simulator; LPJ-GUESS) with local data to, firstly, test whether the model can explain IAVcw and seasonal carbon and water exchange from direct environmental factors only. Initial model runs showed low correlations with estimated annual gross primary productivity (GPP) and annual actual evapotranspiration (AET), while monthly and daily fluxes showed high correlations. The model underestimated GPP and AET during winter and drought events. Secondly, we adapted the temperature inhibition function of photosynthesis to account for the observation that at this particular site, trees continue to assimilate at very low atmospheric temperatures (up to daily averages of −10 °C), resulting in a net carbon sink in winter. While we were able to improve daily and monthly simulations during winter by lowering the modelled minimum temperature threshold for photosynthesis, this did not increase explained IAVcw at the site. Thirdly, we implemented three alternative hypotheses concerning water uptake by plants in order to test which one best corresponds with the data. In particular, we analyse the effects during the 2003 heatwave. These simulations revealed a strong sensitivity of the modelled fluxes during dry and warm conditions, but no single formulation was consistently superior in reproducing the data for all timescales and the overall model–data match for IAVcw could not be improved. Most probably access to deep soil water leads to higher AET and GPP simulated during the heatwave of 2003. We conclude that photosynthesis at lower temperatures than assumed in most models can be important for winter carbon and water fluxes in pine forests. Furthermore, details of the model representations of water uptake, which are often overlooked, need further attention, and deep water access should be treated explicitly.
In recent years, there have been prominent calls for a new social contract that accords a more central role to citizens in health research. Typically, this has been understood as citizens and patients having a greater voice and role within the standard research enterprise. Beyond this, however, it is important that the renegotiated contract specifically addresses the oversight of a new, path-breaking approach to health research: participant-led research. In light of the momentum behind participant-led research and its potential to advance health knowledge by challenging and complementing traditional research, it is vital for all stakeholders to work together in securing the conditions that will enable it to flourish.
Combination chemotherapy with gemcitabine and cisplatin in patients with metastatic urothelial cancer of the bladder frequently results in the development of acquired drug resistance. Availability of cell culture models with acquired resistance could help to identify candidate treatments for an efficient second-line therapy. Six cisplatin- and six gemcitabine-resistant cell lines were established. Cell viability assays were performed to evaluate the sensitivity to 16 different chemotherapeutic substances. The activity of the drug transporter ATP-binding cassette transporter, subfamily B, member 1 (ABCB1, a critical mediator of multidrug resistance in cancer) was evaluated using fluorescent ABCB1 substrates. For functional assessment, cells overexpressing ABCB1 were generated by transduction with a lentiviral vector encoding for ABCB1, while zosuquidar was used for selective inhibition. In this study, 8 of 12 gemcitabine- or cisplatin-resistant cell lines were cross-resistant to carboplatin, 5 to pemetrexed, 4 to methotrexate, 3 to oxaliplatin, 5-fluorouracil, and paclitaxel, and 2 to cabazitaxel, larotaxel, docetaxel, topotecan, doxorubicin, and mitomycin c, and 1 of 12 cell lines was cross-resistant to vinflunine and vinblastine. In one cell line with acquired resistance to gemcitabine (TCC-SUPrGEMCI20), cross-resistance seemed to be mediated by ABCB1 expression. Our model identified the vinca alkaloids vinblastine and vinflunine, in Europe an already approved second-line therapeutic for metastatic bladder cancer, as the most effective compounds in urothelial cancer cells with acquired resistance to gemcitabine or cisplatin. These results demonstrate that this in vitro model can reproduce clinically relevant results and may be suitable to identify novel substances for the treatment of metastatic bladder cancer.
Injury of the sciatic nerve results in regulations of pro- and anti-oxidative enzymes at sites of nociceptive signaling including the injured nerve, dorsal root ganglia (DRGs), dorsal horn of the spinal cord, thalamus and somatosensory cortex (Valek et al., 2015) [1]. The present DiB paper shows immunohistochemistry of redoxins including peroxiredoxins (Prdx1–6), glutaredoxins (Glrx1, 2, 3, 5), thioredoxins (Txn1, 2) and thioredoxin reductases (Txnrd1, 2) in the DRGs, spinal cord and sciatic nerve and thalamus in naïve mice and 7 days after Spared sciatic Nerve Injury (SNI) in control mice (Hif1α-flfl) and in mice with a specific deletion of hypoxia inducible factor 1 alpha (SNS-HIF1α−/−) in DRG neurons. The sciatic nerves were immunostained for the respective redoxins and counterstained with hematoxylin. The redoxin immunoreactivity was quantified with ImageJ. For the DRGs and spinal cord the data show the quantitative assessment of the intensity of redoxin immunoreactivity transformed to rainbow pseudocolors. In addition, some redoxin examples of the ipsi and contralateral dorsal and ventral horns of the lumbar spinal cord and some redoxin examples of the thalamus are presented.
This article focuses primarily on three areas: First the article deals with Alfred Döblin's concept of the novel and the function of the montage technique from his perspective. Secondly, the article draws attention to the fact that Alfred Döblin, a neurologist by profession, who later dedicated himself exclusively to his writing, used the montage technique intensively in his great city novel Berlin Alexanderplatz. The technique, which operates at different levels of language, narrative technique and plot, is demonstrated by selected examples from the novel. In each case the intention of the novelist is discussed. The article considers whether individual accumulating elements accord with the wholeness of the novel, and if so, how this interesting synthesis occurs. The final focus is on his efforts to use the montage technique to portray the big city. In the case of Berlin Alexanderplatz, this effort ultimately ends with a big city epic. In this study, we consider how Döblin used the montage technique in Berlin Alexanderplatz, which was central, and new for German literature at that time. Additionally, narrative styles and techniques as parables, paraboles, sound associations, word and rhyme repetition and relevant passages are supported by quotations from the novel.
This study attempts to determine what methodological approach is suitable for studying speeches about Germanness that were written in Germany in the 1980s. The corpus of the speeches was chosen to cover multiple areas and disciplines. It includes literary, political and historiographical speeches authored by G. Grass ('Geschenkte Freiheit'), M. Walser ('Über Deutschland reden'), R. von Weizsäcker ('Der 8. Mai 1945'), E. Nolte ('Vergangenheit, die nicht vergehen will') and H. Lübbe ('Der Nationalsozialismus im Bewußtsein der deutschen Gegenwart'). The study illustrates the limitations of the ideological and purely disciplinary methodological approach. Instead it seeks a starting point for an analysis which proceeds in an intertextual and interdisciplinary manner.
The tragedy 'König Ottokars Glück und Ende' by the Austrian poet Franz Grillparzer is often viewed as an exclusively male drama. Nevertheless, it does contain female characters, including the two wives of the Přemyslid King Otakar I – Margaret of Austria and Kunigunda of Galicia. The first of these in particular is a somewhat ambiguous character, whose interpretation raises a number of questions. The aim of this study is to outline the problems associated with interpreting the character of Margaret and to find a character in Czech historical literature who is similar to Grillparzer's Margaret.
Bohemian and Moravian archives and libraries represent a rich resource of medieval texts on the plague. Advice, recommendations and recipes for avoiding the plague (prophylaxis), as well as instructions on how to treat it (therapy), can be found in many manuscripts from the 14th–16th centuries. An example of a varied approach to this topic can be found in the plague tractates contained in the Křivoklát manuscript I. b. 25 and the Olomouc manuscript M. I. 650. This article describes the origin and presentation of the information in the manuscripts, as well as the graphic arrangement of the text.
Biomedical data obtained during cell experiments, laboratory animal research, or human studies often display a complex distribution. Statistical identification of subgroups in research data poses an analytical challenge. Here were introduce an interactive R-based bioinformatics tool, called “AdaptGauss”. It enables a valid identification of a biologically-meaningful multimodal structure in the data by fitting a Gaussian mixture model (GMM) to the data. The interface allows a supervised selection of the number of subgroups. This enables the expectation maximization (EM) algorithm to adapt more complex GMM than usually observed with a noninteractive approach. Interactively fitting a GMM to heat pain threshold data acquired from human volunteers revealed a distribution pattern with four Gaussian modes located at temperatures of 32.3, 37.2, 41.4, and 45.4 °C. Noninteractive fitting was unable to identify a meaningful data structure. Obtained results are compatible with known activity temperatures of different TRP ion channels suggesting the mechanistic contribution of different heat sensors to the perception of thermal pain. Thus, sophisticated analysis of the modal structure of biomedical data provides a basis for the mechanistic interpretation of the observations. As it may reflect the involvement of different TRP thermosensory ion channels, the analysis provides a starting point for hypothesis-driven laboratory experiments.
Computed ABC analysis for rational selection of most informative variables in multivariate data
(2015)
Objective: Multivariate data sets often differ in several factors or derived statistical parameters, which have to be selected for a valid interpretation. Basing this selection on traditional statistical limits leads occasionally to the perception of losing information from a data set. This paper proposes a novel method for calculating precise limits for the selection of parameter sets.
Methods: The algorithm is based on an ABC analysis and calculates these limits on the basis of the mathematical properties of the distribution of the analyzed items. The limits implement the aim of any ABC analysis, i.e., comparing the increase in yield to the required additional effort. In particular, the limit for set A, the "important few", is optimized in a way that both, the effort and the yield for the other sets (B and C), are minimized and the additional gain is optimized.
Results: As a typical example from biomedical research, the feasibility of the ABC analysis as an objective replacement for classical subjective limits to select highly relevant variance components of pain thresholds is presented. The proposed method improved the biological interpretation of the results and increased the fraction of valid information that was obtained from the experimental data.
Conclusions: The method is applicable to many further biomedical problems including the creation of diagnostic complex biomarkers or short screening tests from comprehensive test batteries. Thus, the ABC analysis can be proposed as a mathematically valid replacement for traditional limits to maximize the information obtained from multivariate research data.
In der Lenau-Forschung gibt es verschiedene Deutungsansätze des Epos "Die Albigenser". Dabei wurde die Rolle der einzelnen Figuren sowie deren Verhältnis zum epischen Erzähler insofern vernachlässigt, als man kein Versuch unternommen hat, diese in einer klassischen Figurenkonstellation verschiedenen, deutlich voneinander abgegrenzten religiös-weltanschaulichen und poetologischen Positionen zuzuordnen. Ausgehend von einer die bisher formulierten Ansätze modifizierenden Interpretation des epischen Erzählers und unter Rückgriff auf Konstellationen im "Faust "und im "Savonarola" soll in der Folge das äußerst heterogene Figurenarsenal der "Albigenser" in die Gesamtdeutung des Versepos mit einbezogen werden. Dabei stellt sich die Frage nach dem spezifischen Verhältnis der beiden Lager in Fragen der Religion, Moral und Kunst: Einer katholischen Position, die eine Religion der Liebe vertritt, die Menschen belehren und bekehren will und der Kunst dabei eine wichtige Rolle zuerkennt, steht - so die erste These der folgenden Untersuchung - eine Position der Ketzer gegenüber, die im Kampf gegen die etablierte Kirche aggressiv, intolerant und eher kunstfeindlich auftritt. In unbestimmtem Verhältnis zu diesen beiden Konfliktparteien stehen die Troubadours, die sich durch einen weitgehenden religiösen Indifferentismus, eine liberale Grundhaltung und ein Kunstverständnis auszeichnen, das jegliche Funktionalisierung zugunsten rein ästhetischer Positionen ablehnt. Jeder dieser drei Positionen - so die zweite These dieses Beitrags - werden im Rahmen der "Albigenser" Stärken und Schwächen zugesprochen, und auf Basis einer kalkulierten Vielstimmigkeit soll offen bleiben, welchem Konzept von Dichtung der Vorrang gebührt.
Background: Plant hormones are well known regulators which balance plant responses to abiotic and biotic stresses. We investigated the role of abscisic acid (ABA) in resistance of barley (Hordeum vulgare L.) against the plant pathogenic fungus Magnaporthe oryzae.
Results: Exogenous application of ABA prior to inoculation with M. oryzae led to more disease symptoms on barley leaves. This result contrasted the finding that ABA application enhances resistance of barley against the powdery mildew fungus. Microscopic analysis identified diminished penetration resistance as cause for enhanced susceptibility. Consistently, the barley mutant Az34, impaired in ABA biosynthesis, was less susceptible to infection by M. oryzae and displayed elevated penetration resistance as compared to the isogenic wild type cultivar Steptoe. Chemical complementation of Az34 mutant plants by exogenous application of ABA re-established disease severity to the wild type level. The role of ABA in susceptibility of barley against M. oryzae was corroborated by showing that ABA application led to increased disease severity in all barley cultivars under investigation except for the most susceptible cultivar Pallas. Interestingly, endogenous ABA concentrations did not significantly change after infection of barley with M. oryzae.
Conclusion: Our results revealed that elevated ABA levels led to a higher disease severity on barley leaves to M. oryzae. This supports earlier reports on the role of ABA in enhancing susceptibility of rice to the same pathogen and thereby demonstrates a host plant-independent function of this phytohormone in pathogenicity of monocotyledonous plants against M. oryzae.
Cognitive stability and flexibility are core functions in the successful pursuit of behavioral goals. While there is evidence for a common frontoparietal network underlying both functions and for a key role of dopamine in the modulation of flexible versus stable behavior, the exact neurocomputational mechanisms underlying those executive functions and their adaptation to environmental demands are still unclear. In this work we study the neurocomputational mechanisms underlying cue based task switching (flexibility) and distractor inhibition (stability) in a paradigm specifically designed to probe both functions. We develop a physiologically plausible, explicit model of neural networks that maintain the currently active task rule in working memory and implement the decision process. We simplify the four-choice decision network to a nonlinear drift-diffusion process that we canonically derive from a generic winner-take-all network model. By fitting our model to the behavioral data of individual subjects, we can reproduce their full behavior in terms of decisions and reaction time distributions in baseline as well as distractor inhibition and switch conditions. Furthermore, we predict the individual hemodynamic response timecourse of the rule-representing network and localize it to a frontoparietal network including the inferior frontal junction area and the intraparietal sulcus, using functional magnetic resonance imaging. This refines the understanding of task-switch-related frontoparietal brain activity as reflecting attractor-like working memory representations of task rules. Finally, we estimate the subject-specific stability of the rule-representing attractor states in terms of the minimal action associated with a transition between different rule states in the phase-space of the fitted models. This stability measure correlates with switching-specific thalamocorticostriatal activation, i.e., with a system associated with flexible working memory updating and dopaminergic modulation of cognitive flexibility. These results show that stochastic dynamical systems can implement the basic computations underlying cognitive stability and flexibility and explain neurobiological bases of individual differences.
Introduction: ameloblastoma is a slow growing, painless odontogenic swelling which can attain sizes that result in severe deformities of the craniofacial complex. It is the most commonly encountered odontogenic tumor in Nigeria. Surgical intervention is currently the method of treatment; however identification of altered molecular pathways may inform chemotherapeutic potential. The Protein Patched homolog 1 (PTCH-1) is overexpressed in ameloblastoma. Also, mutation in the MDM2 gene can reduce the tumor suppressor function of p53 and promote ameloblastoma growth. No study however has characterized the molecular profile of African cases of ameloblastoma with a view to developing chemotherapeutic alternatives. The objective was to characterize the PTCH-1 genetic profile of Ameloblastoma in Nigerian patients as a first step in investigating its potential for chemotherapeutic intervention.
Methods: twenty-eight FFPE blocks of ameloblastoma cases from Nigerian patients were prepared for antibody processing to PTCH-1 (Polyclonal Anti-PTCH antibody ab39266) and MDM2 (Monoclonal Anti-MDM2 antibody (2A10) ab16895). Cytoplasmic brown staining was considered as positive for PTCH while nuclear staining was positive for MDM2.
Results: moderate and strong expressions for PTCH in ameloblast and stellate reticulum were 78.6% and 60.7% respectively. Only 3 (10.7%) cases expressed MDM2.
Conclusion: the importance of our study is that it supports, in theory, anti-PTCH/SHH chemotherapeutics for Nigerian ameloblastoma cases and also infers the possible additional use of anti-p53 agents.
Steppes used to cover large areas of Hungary, but most of this vegetation has since been destroyed. In Central Hungary, some patches have survived on ridges in wet meadows. These habitat complexes face profound land use changes and their optimal management regime is uncertain. We identified seven annually mown steppe and wet meadow types according to their grazing regime and history and aimed to answer the following questions: (1) Does grazing have beneficial effects on mown steppes and wet meadows? (2) Should the presently homogeneous management of neighbouring steppes and wet meadows be maintained? (3) Is annual mowing sufficient in assisting the recovery of steppes and wet meadows on former croplands?
We selected three localities for each of the seven vegetation types and sampled them with 50 quadrats (50 × 50 cm) in each locality, making a total of 1,050 quadrats. Vascular plant diversity relations were evaluated using the total number of species per habitat type (species richness) and the average number of species per quadrat (microsite diversity). The effect of grazing and history on microsite diversity was tested with linear mixed-effect models. We used Redundancy Analysis to disentangle the role of grazing intensity and management history on species composition. Plant species were then sorted into functional groups, and the proportions of these groups were used to evaluate community structure.
Our results indicate that mowing alone cannot maintain as high a diversity as the combination of the two land use types, thus grazing should be introduced to non-grazed areas. Steppes, however, were found more sensitive to the intensity of grazing than wet meadows. Under heavy grazing, no increased microsite diversity was detected in the steppes and the proportion of disturbance indicators tended to increase. In contrast, the same grazing intensity resulted in only positive effects in wet meadows. Thus, uniform land use on adjacent steppes and wet meadows is not recommended but intensive grazing should be stopped on steppes. Secondary steppes were less diverse than primary ones and their community structure was also poorer, whereas wet meadows had a better regeneration potential. Thus, mowing alone is an incomplete tool to restore the plant diversity of secondary steppes; they should also be grazed and/or should be supported by other active interventions.
Tagungsbericht "Medium - Medialität - Intermedialität." Tagung der Franz Werfel-StipendiatInnen in der Nachbetreuung in Wien, 27. - 28. März 2015
Am 27. und 28. März 2015 veranstaltete die Wiener Germanistik in Zusammenarbeit mit der Österreichischen Austauschdienst-Gesellschaft in Wien die Tagung der Franz Werfel-StipendiatInnen in der Nachbetreuung zum Thema 'Medium - Medialität - Intermedialität. Beiträge zur österreichischen Kulturgeschichte'.
In der vorliegenden Studie wird die Textsorte ‚didaktisch angelegter fachsprachlicher Text‘ einer korpusbasierten Analyse unterzogen, wobei die Perspektive 'Autor - Text' und Prozesse der Informationsübertragung im Vordergrund stehen. Die theoretische Grundlage bilden zwei Ansätze der Pragmasyntax: (1) Der Ansatz 'Attention-Information-Flow' (vgl. SCHULZE 2004: 549f.) beruht auf dem Gedanken, dass der Textproduzent die Informationen versprachlicht, die seine Aufmerksamkeit anziehen. (2) Das Konzept 'Grammatik der Szenen und Szenarien' (vgl. SCHULZE 1998: 435ff.) bezieht sich auf die Strategien der Versprachlichung, dank derer der Autor für wichtig gehaltene Informationen vermitteln kann. Die Ergebnisse der Korpusanalyse bilden ein Tableau mit Eigenschaften der zu erforschenden Textsorte und die Beschreibung ihrer Auswirkung auf Textgestaltungsprozesse unter dem Aspekt einer effizienten Informationsvermittlung.
Background: Measurement of prostate-specific antigen (PSA) advanced the diagnostic and prognostic potential for prostate cancer (PCa). However, due to PSA’s lack of specificity, novel biomarkers are needed to improve risk assessment and ensure optimal personalized therapy. A set of protein molecules as potential biomarkers was therefore evaluated in serum of PCa patients.
Methods: Serum samples from patients undergoing radical prostatectomy (RPE) for biopsy-proven PCa without neoadjuvant treatment were compared to serum samples from healthy subjects. Preliminary screening of 119 proteins in 10 PCa patients and 10 controls was carried out by the Proteome Profiler Antibody Array. Those markers showing distinct differences between patients and controls were then further evaluated by ELISA in the serum of 165 PCa patients and 19 controls. Uni- and multivariate as well as correlation analysis were performed to test the capability of these molecules to detect disease and predict pathological outcome.
Results: Screening showed that soluble (s)E-cadherin, E-selectin, MMP2, MMP9, TIMP1, TIMP2, Galectin and Clusterin warranted further evaluation. sE-Cadherin, TIMP1, Galectin and Clusterin were significantly over- and MMP9 under-expressed in PCa compared to controls. The concentration of sE-cadherin, MMP2 and Clusterin correlated negatively and that of MMP9 and TIMP1 positively with the Gleason Sum at prostatectomy. Only sE-cadherin significantly correlated with the highest Gleason pattern. Compared to serum PSA, sE-cadherin provided an independent and better matching predictive ability for discriminating PCas with an upgrade at RPE and aggressive tumors with a Gleason Sum ≥7.
Conclusions: sE-cadherin performed most favorably from a large panel of serum proteins in terms of diagnostic and predictive potential in curatively treatable PCa. sE-cadherin merits further investigation as a biomarker for PCa.
A new scorpion species, Euscorpius drenskii sp. nov., is described from the Western Rhodope Mts. in southern Bulgaria. It is characterized by an oligotrichous trichobothrial pattern, which shows a conspicuous loss of one trichobothrium in the external median patellar series (em = 3), also observed in E. carpathicus (Linnaeus, 1767) and the subgenus Alpiscorpius Gantenbein, Fet, Largiadèr & Scholl, 1999. Phylogenetic analysis of 16S rDNA marker sequences does not show any close relationship between these three groups, suggesting that the observed loss of a trichobothrium is an independent event.
Background: From 2008–2013, the European indication for panitumumab required that patients' tumor KRAS exon 2 mutation status was known prior to starting treatment. To evaluate physician awareness of panitumumab prescribing information and how physicians prescribe panitumumab in patients with metastatic colorectal cancer (mCRC), two European multi-country, cross-sectional, observational studies were initiated in 2012: a physician survey and a medical records review. The first two out of three planned rounds for each study are reported.
Methods: The primary objective in the physician survey was to estimate the prevalence of KRAS testing, and in the medical records review, it was to evaluate the effect of test results on patterns of panitumumab use. The medical records review study also included a pathologists' survey.
Results: In the physician survey, nearly all oncologists (299/301) were aware of the correct panitumumab indication and the need to test patients' tumor KRAS status before treatment with panitumumab. Nearly all oncologists (283/301) had in the past 6 months of clinical practice administered panitumumab correctly to mCRC patients with wild-type KRAS status. In the medical records review, 97.5% of participating oncologists (77/79) conducted a KRAS test for all of their patients prior to prescribing panitumumab. Four patients (1.3%) did not have tumor KRAS mutation status tested prior to starting panitumumab treatment. Approximately one-quarter of patients (85/306) were treated with panitumumab and concurrent oxaliplatin-containing chemotherapy; of these, 83/85 had confirmed wild-type KRAS status prior to starting panitumumab treatment. All 56 referred laboratories that participated used a Conformité Européenne-marked or otherwise validated KRAS detection method, and nearly all (55/56) participated in a quality assurance scheme.
Conclusions: There was a high level of knowledge amongst oncologists around panitumumab prescribing information and the need to test and confirm patients' tumors as being wild-type KRAS prior to treatment with panitumumab, with or without concurrent oxaliplatin-containing therapy.
In New South Wales, the Threatened Species Conservation Act 1995 makes provision for the listing of Threatened Ecological Communities (assemblages of species occupying a particular area) as a means to conserving the variety of ecosystems present in the State. Hunter Valley Weeping Myall Woodland is listed as an Endangered Ecological Community under the New South Wales Threatened Species Conservation (TSC) Act 1995 and as a Critically Endangered Ecological Community under the Commonwealth Environment Protection and Biodiversity Conservation (EPBC) Act 1999.
The provenance of populations of Weeping Myall (Acacia pendula, family Fabaceae) in the Hunter Valley has recently been questioned. In this paper we consider the implications of its hypothesized European introduction for listing Hunter Valley Weeping Myall Woodland under the TSC and EPBS Acts. The recognition of any community is contingent on the identification of both a particular assemblage of species and the critical environmental factors that determine their co-occurrence (the area the community occupies in environmental space). Acacia pendula is one of a range of semiarid species which are primarily distributed west of the Great Dividing Range but also occur on Permian sediments in areas receiving the lowest rainfall of the Hunter Valley floor. On this basis we argue there is sufficient evidence to support the listing of Hunter Valley Weeping Myall Woodland under both Acts.
Hemidactylus frenatus is an Asian gecko species that has invaded many tropical regions to become one of the most widespread lizards worldwide. This species has dispersed across the Pacific Ocean to reach Hawaii and subsequently Mexico and other Central American countries. More recently, it has been reported from northwestern South America. Using 12S and cytb mitochondrial DNA sequences I found that South American and Galápagos haplotypes are identical to those from Hawaii and Papua New Guinea, suggesting a common Melanesian origin for both Hawaii and South America. Literature records suggest that H. frenatus arrived in Colombia around the mid-‘90s, dispersed south into Ecuador in less than five years, and arrived in the Galápagos about one decade later.
Understanding factors that structure regional biodiversity is important for linking ecological and biogeographic processes. Our objective was to explore regional patterns in riverine benthic invertebrate assemblages in relation to their broad positioning along the river network and examine differences in composition, biodiversity (alpha and beta diversity), and environmental drivers. We up-scaled methods used to examine patterns in metacommunity structure (Elements of Metacommunity Structure framework) to examine faunal distribution patterns at the regional extent for 168 low-mountain stream invertebrate assemblages in central Germany. We then identified the most influential environmental factors using boosted regression trees. Faunal composition patterns were compartmentalised (Clementsian or quasi-Clementsian), with little difference from headwaters to large rivers, potentially reflecting the regional scale of the study, by crossing major catchment boundaries and incorporating different species pools. While idealised structures did not vary, environmental drivers of composition varied considerably between river sections and with alpha diversity. Prediction was substantially weaker, and the importance of space was greater, in large rivers compared to other sections suggesting a weakening in species sorting downstream. Further, there was a stronger transition in composition than for alpha diversity downstream. The stronger links with regional faunal composition than with richness further emphasises the importance of considering the alternative ways in which anthropogenic stressors are operating to affect biodiversity patterns. Our approach allowed bridging the gap between local (or metacommunity) and regional scales, providing key insights into drivers of regional biodiversity patterns.
Little work has been done on large-scale patterns of stream insect richness in China. We explored the influence of climatic and catchment-scale factors on stream insect (Ephemeroptera, Plecoptera, Trichoptera; EPT) richness across mid-latitude China. We assessed the predictive ability of climatic, catchment land cover and physical structure variables on genus richness of EPT, both individually and combined, in 80 mid-latitude Chinese streams, spanning a 3899-m altitudinal gradient. We performed analyses using boosted regression trees and explored the nature of their influence on richness patterns. The relative importance of climate, land cover, and physical factors on stream insect richness varied considerably between the three orders, and while important for Ephemeroptera and Plecoptera, latitude did not improve model fit for any of the groups. EPT richness was linked with areas comprising high forest cover, elevation and slope, large catchments and low temperatures. Ephemeroptera favoured areas with high forest cover, medium-to-large catchment sizes, high temperature seasonality, and low potential evapotranspiration. Plecoptera richness was linked with low temperature seasonality and annual mean, and high slope, elevation and warm-season rainfall. Finally, Trichoptera favoured high elevation areas, with high forest cover, and low mean annual temperature, seasonality and aridity. Our findings highlight the variable role that catchment land cover, physical properties and climatic influences have on stream insect richness. This is one of the first studies of its kind in Chinese streams, thus we set the scene for more in-depth assessments of stream insect richness across broader spatial scales in China, but stress the importance of improving data availability and consistency through time.
We discuss the behavior of dynamically-generated charmed baryonic resonances in matter within a unitarized coupled-channel model consistent with heavy-quark spin symmetry. We analyze the implications for the formation of D-meson bound states in nuclei and the propagation of D mesons in heavy-ion collisions from RHIC to FAIR energies.
Pitfall trapping in the National Park Thy, north-western Jutland, Denmark, in 2011 and 2013 revealed 3654 specimens of the harvestman Nelima gothica. In most European countries, including Denmark, this species has been considered rare and little information is available on its biology. The species was found predominantly in the yellow dune habitat close to the North Sea coast. Here it could be either very abundant or completely absent at localities only a few kilometres apart. It also occurred in lower numbers in the grey dunes and the dune heathland, and was rare in managed grassland; it disappeared from habitats further inland. In the yellow dunes high numbers were recorded especially in rather dense Ammophila arenaria vegetation not disturbed by sand shifting. The phenology follows the typical pattern of North-European Phalangiidae and Leiobuninae: an annual life-cycle with juveniles developing through late spring and summer months, reproduction in autumn and hibernation in the egg stage. The findings suggest that N. gothica may be found all along the coastal dunes of western Denmark and possibly the Wadden Sea area, though it may only locally reach high abundances. Earlier records also included the coasts of eastern Denmark.
Songs in passerine birds are important for territory defense and mating. Speciation rates in oscine passerines are so high, due to cultural evolution, that this bird lineage makes up half of the extant bird species. Leaf warblers are a speciose Old-World passerine family of limited morphological differentiation, so that songs are even more important for species delimitation. We took 16 sonographic traits from song recordings of 80 leaf warbler taxa and correlated them with 15 potentially explanatory variables, pairwise, and in linear models. Based on a well-resolved molecular phylogeny of the same taxa, all pairwise correlations were corrected for relatedness with phylogenetically independent contrasts and phylogenetic generalized linear models were used. We found a phylogenetic signal for most song traits, but a strong one only for the duration of the longest and of the shortest element, which are presumably inherited instead of learned. Body size of a leaf warbler species is a constraint on song frequencies independent of phylogeny. At least in this study, habitat density had only marginal impact on song features, which even disappeared through phylogenetic correction. Maybe most leaf warblers avoid the deterioration through sound propagation in dense vegetation by singing from exposed perches. Latitudinal (and longitudinal) extension of the breeding ranges was correlated with most song features, especially verse duration (longer polewards and westwards) and complexity (lower polewards). Climate niche or expansion history might explain these correlations. The number of different element types per verse decreases with elevation, possibly due to fewer resources and congeneric species at higher elevations.
The Muskoka Initiative – or the Maternal, Newborn and Child Health (MNCH) Initiative has been a flagship foreign policy strategy of the Harper Conservatives since it was introduced in 2010. However, the maternal health initiative has been met with a number of key criticisms in relation to its failure to address the sexual and reproductive health needs of women in the Global South2. In this article, I examine these criticisms and expose the prevalent and problematic discourse employed in Canadian policy papers and official government speeches pertaining to the MNCH Initiative. I examine the embodiment of the MNCH and how these references to women’s bodies as “walking wombs” facilitate: the objectification and ‘othering’ of women as mothers and childbearers; a discourse of ‘saving mothers’ in a paternalistic and essentialist language; and the purposeful omission of gender equality. Feminist International Relations (IR) and post-colonial literature, as well as critical/feminist Canadian foreign policy scholarship are employed in this paper to frame these critiques.
The Sonic Hedgehog (SHH) pathway plays a central role in the developing mammalian CNS. In our study, we aimed to investigate the spatiotemporal SHH pathway expression pattern in human fetal brains. We analyzed 22 normal fetal brains for Shh, Patched, Smoothened, and Gli1-3 expression by immunohistochemistry. In the telencephalon, strongest expression of Shh, Smoothened, and Gli2 was found in the cortical plate (CP) and ventricular zone. Patched was strongly upregulated in the ventricular zone and Gli1 in the CP. In the cerebellum, SHH pathway members were strongly expressed in the external granular layer (EGL). SHH pathway members significantly decreased over time in the ventricular and subventricular zone and in the cerebellar EGL, while increasing levels were found in more superficial telencephalic layers. Our findings show that SHH pathway members are strongly expressed in areas important for proliferation and differentiation and indicate a temporal expression gradient in telencephalic and cerebellar layers probably due to decreased proliferation of progenitor cells and increased differentiation. Our data about the spatiotemporal expression of SHH pathway members in the developing human brain serves as a base for the understanding of both normal and pathological CNS development.
The article discusses recent history developments in Central and Eastern Europe more than a quarter century after the political change of 1989 on the development of programs at former traditional departments of German studies, the training of teachers for German as a foreign language and the growing importance of German for specific purposes.
Numerous studies reported a strong link between working memory capacity (WMC) and fluid intelligence (Gf), although views differ in respect to how close these two constructs are related to each other. In the present study, we used a WMC task with five levels of task demands to assess the relationship between WMC and Gf by means of a new methodological approach referred to as fixed-links modeling. Fixed-links models belong to the family of confirmatory factor analysis (CFA) and are of particular interest for experimental, repeated-measures designs. With this technique, processes systematically varying across task conditions can be disentangled from processes unaffected by the experimental manipulation. Proceeding from the assumption that experimental manipulation in a WMC task leads to increasing demands on WMC, the processes systematically varying across task conditions can be assumed to be WMC-specific. Processes not varying across task conditions, on the other hand, are probably independent of WMC. Fixed-links models allow for representing these two kinds of processes by two independent latent variables. In contrast to traditional CFA where a common latent variable is derived from the different task conditions, fixed-links models facilitate a more precise or purified representation of the WMC-related processes of interest. By using fixed-links modeling to analyze data of 200 participants, we identified a non-experimental latent variable, representing processes that remained constant irrespective of the WMC task conditions, and an experimental latent variable which reflected processes that varied as a function of experimental manipulation. This latter variable represents the increasing demands on WMC and, hence, was considered a purified measure of WMC controlled for the constant processes. Fixed-links modeling showed that both the purified measure of WMC (β = .48) as well as the constant processes involved in the task (β = .45) were related to Gf. Taken together, these two latent variables explained the same portion of variance of Gf as a single latent variable obtained by traditional CFA (β = .65) indicating that traditional CFA causes an overestimation of the effective relationship between WMC and Gf. Thus, fixed-links modeling provides a feasible method for a more valid investigation of the functional relationship between specific constructs.
Background: Hypoxia is a key driver for infiltrative growth in experimental gliomas. It has remained elusive whether tumor hypoxia in glioblastoma patients contributes to distant or diffuse recurrences. We therefore investigated the influence of perioperative cerebral ischemia on patterns of progression in glioblastoma patients.
Methods: We retrospectively screened MRI scans of 245 patients with newly diagnosed glioblastoma undergoing resection for perioperative ischemia near the resection cavity. 46 showed relevant ischemia nearby the resection cavity. A control cohort without perioperative ischemia was generated by a 1:1 matching using an algorithm based on gender, age and adjuvant treatment. Both cohorts were analyzed for patterns of progression by a blinded neuroradiologist.
Results: The percentage of diffuse or distant recurrences at first relapse was significantly higher in the cohort with perioperative ischemia (61.1%) compared to the control cohort (19.4%). The results of the control cohort matched well with historical data. The change in patterns of progression was not associated with a difference in survival.
Conclusions: This study reveals an unrecognized association of perioperative cerebral ischemia with distant or diffuse recurrence in glioblastoma. It is the first clinical study supporting the concept that hypoxia is a key driver of infiltrative tumor growth in glioblastoma patients.
Background: Detailed injury data are not available for international tournaments in field hockey. We investigated the epidemiology of field hockey injuries during major International Hockey Federation (Fédération Internationale de Hockey, FIH) tournaments in 2013.
Materials: and methods FIH injury reports were used for data collection. All major FIH tournaments for women (n=5) and men (n=11) in 2013 were included. The main focus of this study was to assess the pattern, time, site on the pitch, body site and mechanism of each of the injuries. We calculated the average number of injuries per match and the number of injuries per 1000 player match hours.
Results: The average number of injuries was 0.7 (95% CI 0.5 to 1.0) per match in women's tournaments and 1.2 (95% CI 0.8 to 1.7) per match in men's tournaments. The number of injuries per 1000 player match hours ranged from 23.4 to 44.2 (average 29.1; 95% CI 18.6 to 39.7) in women and 20.8 to 90.9 (average 48.3; 95% CI 30.9 to 65.8) in men. Most injuries occurred in the circle (n=25, 50%, in women, n=95, 51%, in men). The rate of injuries increased after the first quarter. Injuries to the head and face (n=20, 40%) were most common in women. The head/face (n=51, 27%) and the thigh/knee (n=52, 28%) were equally affected in men. The ball caused the most injuries, followed by the stick, collisions and tripping/falling. There were no deaths or injuries that required hospital treatment in the entire cohort.
Summary: Field hockey has a low incidence of acute injuries during competition.
BACKGROUND: Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, has shown superior efficacy to etanercept with similar safety in moderate to severe plaque psoriasis (FIXTURE study).
OBJECTIVE: We sought to directly compare efficacy and safety of secukinumab versus ustekinumab.
METHODS: In this 52-week, double-blind study (NCT02074982), 676 subjects were randomized 1:1 to subcutaneous injection of secukinumab 300 mg or ustekinumab per label. Primary end point was 90% or more improvement from baseline Psoriasis Area and Severity Index (PASI) score (PASI 90) at week 16.
RESULTS: Secukinumab (79.0%) was superior to ustekinumab (57.6%) as assessed by PASI 90 response at week 16 (P < .0001). The 100% improvement from baseline PASI score at week 16 was also significantly greater with secukinumab (44.3%) than ustekinumab (28.4%) (P < .0001). The 75% or more improvement from baseline PASI score at week 4 was superior for secukinumab (50.0%) versus ustekinumab (20.6%) (P < .0001). Percentage of subjects with the Dermatology Life Quality Index score 0/1 (week 16) was significantly higher with secukinumab (71.9%) than ustekinumab (57.4%) (P < .0001). The safety profile of secukinumab was comparable with ustekinumab and consistent with pivotal phase III secukinumab studies.
LIMITATIONS: The study was not placebo-controlled and of short-term duration.
CONCLUSIONS: Secukinumab is superior to ustekinumab in clearing skin of subjects with moderate to severe psoriasis and improving health-related quality of life with a comparable safety profile over 16 weeks.
Traditional chinese medicine and herbal hepatotoxicity: a tabular compilation of reported cases
(2015)
Traditional Chinese Medicine (TCM) with its focus on herbal use became popular worldwide. Treatment was perceived as safe, with neglect of rare adverse reactions including liver injury. To compile worldwide cases of liver injury by herbal TCM, we undertook a selective literature search in the PubMed database and searched for the items Traditional Chinese Medicine, TCM, Traditional Asian Medicine, and Traditional Oriental Medicine, also combined with the terms herbal hepatotoxicity or herb induced liver injury. The search focused primarily on English-language case reports, case series, and clinical reviews. We identified reported hepatotoxicity cases in 77 relevant publications with 57 different herbs and herbal mixtures of TCM, which were further analyzed for causality by the Council for International Organizations of Medical Sciences (CIOMS) scale, positive reexposure test results, or both. Causality was established for 28/57 different herbs or herbal mixtures, Bai Xian Pi, Bo He, Ci Wu Jia, Chuan Lian Zi, Da Huang, Gan Cao, Ge Gen, Ho Shou Wu, Huang Qin, Hwang Geun Cho, Ji Gu Cao, Ji Xue Cao, Jin Bu Huan, Jue Ming Zi, Jiguja, Kudzu, Ling Yang Qing Fei Keli, Lu Cha, Rhen Shen, Ma Huang, Shou Wu Pian, Shan Chi, Shen Min, Syo Saiko To, Xiao Chai Hu Tang, Yin Chen Hao, Zexie, and Zhen Chu Cao. In conclusion, this compilation of liver injury cases establishes causality for 28/57 different TCM herbs and herbal mixtures, aiding diagnosis for physicians who care for patients with liver disease possibly related to herbal TCM.