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Der Band untersucht die Ursachen, Ausprägungen und Reaktionen auf die Entstehung bzw. Erstarkung populistischer Parteien und Bewegungen in Deutschland und Ostmitteleuropa.
Inhaltsverzeichnis:
Arthur Benz: Populismus als Herausforderung für Wissenschaft und Praxis - Einleitung
Dirk Jörke: Populismus – Ursachen und falsche Antworten
Michael Edinger: Mobilisierung gegen das Establishment. Zu einem Wesensmerkmal populistischer Strömungen
Claudia Landwehr und Nils D. Steiner: Populismus – eine Nachfrageperspektive
Joachim Klose: Ein Land, zwei Perspektiven? Zum Populismusin Ost- und Westdeutschland
Petra Guasti und Lenka Buštíková: Populismus in Ostmitteleuropa und der Verzicht auf Politik
Previous research on scalar implicature has primarily relied on metalinguistic judgment tasks and found varying rates of such inferences depending on the nature of the task and contextual manipulations. This paper introduces a novel interactive paradigm involving both a production and a comprehension component, thereby fixing a precise conversational context.
The main research question is what is reliably communicated by some in this communicative setting, when the quantifier occurs in unembedded positions as well as embedded positions. Our new paradigm involves an action-based task from which participants’ interpretation of utterances can be inferred. It incorporates a game–theoretic design, including a precise model to predict participants’ behaviour in the experimental context.
Our study shows that embedded and unembedded implicatures are reliably communicated by some. We propose two cognitive principles which describe what can be left unsaid. In our experimental context, a production strategy based on these principles is more efficient (with equal communicative success and shorter utterances) than a strategy based on literal descriptions.
In recent years, experimental research has demontrated great variability in the rates of scalar inferences across different triggering expressions (Doran et al. 2009, 2012, van Tiel et al. 2016). These studies have been taken as evidence against the so-called uniformity assumption, which posits that scalar implicature is triggered by a single mechanism and that the behaviour of one scale should generalize to the whole family of scales. In the following, we present an experimental study that tests negative strengthening for a variety of strong scalar terms, following up on van Tiel et al. (2016). For example, we tested whether the statement John is not brilliant is strengthened to mean that John is not intelligent (see especially Horn 1989). We show that endorsement rates of the scalar implicature (e.g., John is intelligent but not brilliant) are anti-correlated with endorsements of negative strengthening. Further, we demonstrate that a modified version of the uniformity hypothesis taking into account negative strengthening is consistent with van Tiel et al.’s data. Therefore, variation across scales may be more systematic than suggested by the van Tiel et al. study.
"Sozialwissenschaftlich aufschlussreich sind für mich nicht Zustände, sondern Verläufe – oder Zustände nur im Zusammenhang von Verläufen. Theorien, die Strukturen oder Ereignisse als freistehende Unikate in einem feststehenden Ereignis- und Möglichkeitsraum behandeln, können fundamental in die Irre führen. Alles Soziale spielt sich in der Zeit ab, entfaltet sich mit der Zeit und wird in und mit ihr sich selber ähnlicher. Was wir heute sehen, können wir nur verstehen, wenn wir wissen, wie es gestern ausgesehen hat und auf welchem Weg es sich befindet. Alles, was vorfindlich ist, ist immer auf einem Entwicklungspfad unterwegs. Auf diesen kommt es entscheidend an." ...
Background: The present study aims to elucidate the state of gender equality in high-quality research by analyzing the representation of female authorships in the last decade (from 2008 to 2016).
Methods: Based on the Gendermetrics platform, 293,557 research articles from 54 journals listed in the Nature Index were considered covering the categories Life Science, Multidisciplinary, Earth & Environmental and Chemistry. The core method was the combined analysis of the proportion of female authorships and the female-to-male odds ratio for first, co- and last authorships. The distribution of prestigious authorships was measured by the Prestige Index.
Results: 29.8% of all authorships and 33.1% of the first, 31.8% of the co- and 18.1% of the last authorships were held by women. The corresponding female-to-male odds ratio is 1.19 (CI: 1.18–1.20) for first, 1.35 (CI: 1.34–1.36) for co- and 0.47 (CI: 0.46–0.48) for last authorships. Women are underrepresented at prestigious authorships compared to men (Prestige Index = -0.42). The underrepresentation accentuates in highly competitive articles attracting the highest citation rates, namely, articles with many authors and articles that were published in highest-impact journals. More specifically, a large negative correlation between the 5-Year-Impact-Factor of a journal and the female representation at prestigious authorships was revealed (r(52) = -.63, P < .001). Women publish fewer articles compared to men (39.0% female authors are responsible for 29.8% of all authorships) and are underrepresented at productivity levels of more than 2 articles per author. Articles with female key authors are less frequently cited than articles with male key authors. The gender-specific differences in citation rates increase the more authors contribute to an article. Distinct differences at the journal, journal category, continent and country level were revealed. The prognosis for the next decades forecast a very slow harmonization of authorships odds between the two genders.
Objective: The present study aims to elucidate the state of gender equality in high-quality dermatological research by analysing the representation of female authorships from January 2008 to May 2017.
Design: Retrospective, descriptive study.
Setting: 113 189 male and female authorships from 23 373 research articles published in 23 dermatological Q1 journals were analysed with the aid of the Gendermetrics Platform.
Results: 43.0% of all authorships and 50.2% of the firstauthorships, 43.7% of the coauthorships and 33.1% of the last authorships are held by women. The corresponding female-to-male ORs are 1.41 (95% CI 1.37 to 1.45) for first authorships, 1.07 (95% CI 1.04 to 1.10) for coauthorships and 0.60 (95% CI 0.58 to 0.62) for last authorships. The annual growth rates are 1.74% overall and 1.45% for first authorships, 1.53% for coauthorships and 2.97% for last authorships. Women are slightly under-represented at prestigious authorships compared with men (Prestige Index=−0.11). The under-representation remains stable in highly competitive articles attracting the highest citation rates, namely, articles with many authors and articles that were published in highest-impact journals. Multiauthor articles with male key authors are only slightly more frequently cited than those with female key authors. Women publish slightly fewer papers compared with men (47.2% women hold 43.0% of the authorships). At the level of individual journals, there is a high degree of uniformity in gender-specific authorship odds. By contrast, distinct differences at country level were revealed. The prognosis for the next decades forecasts a consecutive harmonisation of authorship odds between the two genders.
Conclusions: In high-quality dermatological research, the integration of female scholars is advanced as compared with other medical disciplines. A gender gap consists mainly in the form of a career dichotomy, with many female early career researchers and few women in academic leadership positions. However, this gender gap has been narrowed in the last decade and will likely be further reduced in the future.
Subduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence for contributions of oxidising slab agents to melts trapped in the sub-arc mantle. Measurements of sulfur (S) valence state in sub-arc mantle peridotites identify sulfate, both as crystalline anhydrite (CaSO4) and dissolved SO42− in spinel-hosted glass (formerly melt) inclusions. Copper-rich sulfide precipitates in the inclusions and increased Fe3+/∑Fe in spinel record a S6+–Fe2+ redox coupling during melt percolation through the sub-arc mantle. Sulfate-rich glass inclusions exhibit high U/Th, Pb/Ce, Sr/Nd and δ34S (+ 7 to + 11‰), indicating the involvement of dehydration products of serpentinised slab rocks in their parental melt sources. These observations provide a link between liberated slab components and oxidised arc magmas.
Alternative Questions with "or not" (NAQ) convey a cornering effect, which is not found with they polar counterparts (PQ). This effect has been claimed to consist of two parts (Biezma 2009): NAQs (i) cannot be used discourse-initially and (ii) they do not license followup questions/subquestions.
In this paper, we ask the following: Are both parts of cornering linked to the same property of NAQs? Or do they reflect distinct linguistic phenomena? We explore the issue by comparing the behavior of NAQs to Complement Alternative Questions (CAQ), a type of question that, like NAQs, presents logically opposite alternatives but, unlike NAQs, fully spells out the second one. Results from two experiments suggest that both parts of cornering can instead be explained in terms of independent semantic and pragmatic principles, which operate beyond the domain of alternative questions.
Sentences containing subjective predicates - e.g., "The movie was awesome"” - are intuitively anchored to a particular perspective; this makes them different from sentences describing objective facts - e.g., "The movie was set in 1995".
While authors have long debated on whether this intuition tracks a lexical distinction between subjective and factual predicates, much remains to be explored on whether, and how, the difference between these two assertions is reflected at the illocutionary level. Relying on evidence from two experiments, we show that assertions containing subjective predicates display different discourse behavior from objective assertions. We take these findings to support the idea that SAs should be assigned a special illocutionary profile, unveiling a genuine empirical difference between subjective and factual speech.
This paper analyses whether the post-crisis regulatory reforms developed by global-standard-setting bodies have created appropriate incentives for different types of market participants to centrally clear Over-The-Counter (OTC) derivative contracts. Beyond documenting the observed facts, we analyze four main drivers for the decision to clear: 1) the liquidity and riskiness of the reference entity; 2) the credit risk of the counterparty; 3) the clearing member’s portfolio net exposure with the Central Counterparty Clearing House (CCP) and 4) post trade transparency. We use confidential European trade repository data on single-name Sovereign Credit Derivative Swap (CDS) transactions, and show that for all the transactions reported in 2016 on Italian, German and French Sovereign CDS 48% were centrally cleared, 42% were not cleared despite being eligible for central clearing, while 9% of the contracts were not clearable because they did not satisfy certain CCP clearing criteria. However, there is a large difference between CCP clearing members that clear about 53% of their transactions and non-clearing members, even those that are subject to counterparty risk capital requirements, that almost never clear their trades. Moreover, we find that diverse factors explain clearing members’ decision to clear different CDS contracts: for Italian CDS, counterparty credit risk exposures matter most for the decision to clear, while for French and German CDS, margin costs are the most important factor for the decision. Clearing members use clearing to reduce their exposures to the CCP and largely clear contracts when at least one of the traders has a high counterparty credit risk.
In December 1965, in a smoke-filled hotel room in Morocco, South African journalist Terry Bell accepted a challenge: to paddle a kayak from London to Tangier. At the time, Terry and his wife Barbara were living as political exiles in London. By August 1967, they agreed it was time to get back to Africa. But they decided to up the ante. Their plan: paddle 11 000 kilometres from England to Dar es Salaam in a 5-metre glass fibre kayak.
A rare flowering event in a stand of Acacia pendula (Weeping Myall) (family Fabaceae, Mimosoideae) from the Hunter Valley of New South Wales is documented. This species flowers poorly in the region and (with the exception of horticultural specimens) has not been observed to fruit and develop viable seed for over a decade. One stand of this threatened Hunter Valley population of Acacia pendula was monitored over a seven month period (January to July 2018) to investigate this poor reproductive output. Despite copious bud production in January and February, the extent and condition of these, and all subsequent flowers rapidly declined, and none progressed to fruit.
Primary reasons for reproductive failure were postulated to be a combination of mass desiccation of capitula following extended dry conditions, infestation by native flower- and phyllode-galling midges and thrips (Asphondylia sp., Dasineura glomerata, Kladothrips rugosus), fungal galls (Uromycladium sp.), caterpillars (Ochrogaster lunifer), and mistletoe (Amyema quandang). Collectively, these stressors appear to be eliminating seed production from the study
population; survival is maintained only by the copious root-suckering observed around most plants, particularly after the pressure from stock grazing (cattle, sheep) has been removed. The age of trees studied, based on measures of girth and comparison with growth rates reported for other semi-arid Acacia, was inferred to be between 50 and 150 years. The level of Amyema quandang (mistletoe) infestation on Acacia trees was independent of tree size, and there was no evidence to suggest that mistletoe density alone influenced flowering progress.
Consequences of these observations on future management of Acacia pendula in the Hunter Valley are briefly discussed.
In this article, we profile an empirically grounded, cognitive approach to immersion in digital fiction by combining text-driven stylistic analysis with insights from theories of cognition and reader-response research. We offer a new analytical method for immersive features in digital fiction by developing deictic shift theory for the affordances of digital media. We also provide empirically substantiated insights to show how immersion is experienced cognitively by using Andy Campbell and Judi Alston’s (2015) digital fiction piece WALLPAPER as a case study. We add ‘interactional deixis’ and ‘audible deixis’ to Stockwell’s (2002) model to account for the multimodal nature of immersion in digital fiction. We also show how extra-textual features can contribute to immersion and thus propose that they should be accounted for when analysing immersion across media. We conclude that the analytical framework and reader response protocol that we develop here can be adapted for application to texts across media.
Summary statement When echolocating under demanding conditions e.g. noisy, narrow space, or cluttered environments, frugivorous bats adapt their call pattern by increasing the call rate within biosonar groups.
Abstract For orientation, echolocating bats emit biosonar calls and use echoes arising from call reflections. They often pattern their calls into groups which increases the rate of sensory feedback over time. Insectivorous bats emit call groups at a higher rate when orienting in cluttered compared to uncluttered environments. Frugivorous bats increase the rate of call group emission when they echolocate in noisy environments. Here, calls emitted by conspecifics potentially interfere with the bat’s biosonar signals and complicate the echolocation behavior. To minimize the information loss followed by signal interference, bats may profit from a temporally increased sensory acquisition rate, as it is the case for the call groups. In frugivorous bats, it remains unclear if call group emission represents an exclusive adaptation to avoid interference by signals from other bats or if it represents an adaptation that allows to orient under demanding environmental conditions. Here, we compared the emission pattern of the frugivorous bat Carollia perspicillata when the bats were flying in noisy versus silent, narrow versus wide or cluttered versus non-cluttered corridors. According to our results, the bats emitted larger call groups and they increased the call rate within the call groups when navigating in narrow, cluttered, or noisy environments. Thus, call group emission represents an adaptive behavior when the bats orient in complex environments.
Strong convergence rates for numerical approximations of stochastic partial differential equations
(2018)
In this thesis and in the research articles which this thesis consists of, respectively, we focus on strong convergence rates for numerical approximations of stochastic partial differential equations (SPDEs). In Part I of this thesis, i.e., Chapter 2 and Chapter 3, we study higher order numerical schemes for SPDEs with multiplicative trace class noise based on suitable Taylor expansions of the Lipschitz continuous coefficients of the SPDEs under consideration. More precisely, Chapter 2 proves strong convergence rates for a linear implicit Euler-Milstein scheme for SPDEs and is based on an unpublished manuscript written by the author of this thesis. This chapter extends an earlier result1 by slightly lowering the assumptions posed on the diffusion coefficient and a different approximation of the semigroup. In Chapter 3 we introduce an exponential Wagner-Platen type numerical scheme for SPDEs and prove that this numerical approximation method converges in the strong sense with oder up to 3/2−. Moreover, we illustrate how the (mixed) iterated stochastic-deterministic integrals, that are part of our numerical scheme, can be simulated exactly under suitable assumptions.
The second part of this thesis, i.e. Chapter 4 and Chapter 5, is devoted to strong convergence rates for numerical approximations of SPDEs with superlinearly growing nonlinearities driven by additive space-time white noise. More specifically, in Chapter 4, we prove strong convergence with rate in the time variable for a class of nonlinearity-truncated numerical approximation schemes for SPDEs and provide examples that fit into our abstract setting like stochastic Allen-Cahn equations. Finally, in Chapter 5, we extend this result with spatial approximations and establish strong convergence rates for a class of full-discrete nonlinearity truncated numerical approximation schemes for SPDEs. Moreover, we apply our strong convergence result to stochastic Allen-Cahn equations and provide lower and upper bounds which show that our strong convergence result can, in general, not essentially be improved.
"... et quod hodie exemplis tuemur, inter exempla erit." Mit diesen Worten beendete der römische Historiograph Publius Cornelius Tacitus die von ihm konzipierte Version der Gallierrede aus dem Jahr 48 n. Chr., die er dem römischen Princeps Claudius in den Mund gelegt hatte. Tacitus griff hier mit den Exempla der Vorfahren ein wichtiges Argument der konservativen römischen Nobilität auf, durch das diese ihr Handeln häufig legitimierte, und ließ es seinen Claudius dafür nutzen, um die Aufnahme von gallischen Notabeln, also eine auf den ersten Blick noch nie dagewesene Neuerung, zu rechtfertigen. Dazu wählte er beispielhafte Episoden aus der römischen Geschichte, die verdeutlichten, dass die Vorfahren selbst ebenfalls Neuerungen zugelassen hatten, die sich im Nachhinein als sehr wichtig für die römischen Erfolge herausgestellt hatten. Damit widersprächen Neuerungen folglich nicht dem mos maiorum, dem für das römische Moralverständnis grundlegenden Wertekanon, sondern seien vielmehr integraler Bestandteil desselben. ...
UNDERSTANDING HOW HOUSEHOLDS REACT TO THE ARRIVAL OF PERMANENT AND TRANSITORY INCOME IS OF INTEREST FOR RESEARCHERS AND REGULATORS. PREVIOUS STUDIES HAD TO USE IMPRECISE SURVEY DATA TO MEASURE CONSUMPTION AND THUS CONCLUSIONS OFTEN DIVERGED. WE LEVERAGE GRANULAR PERSONAL FINANCE MANAGEMENT FINTECH DATA TO TEST FRIEDMAN'S PERMANENT INCOME HYPOTHESIS AND TO ASSESS HOUSEHOLD SPENDING ELASTICITY AND MARGINAL PROPENSITY TO CONSUME FOR VARIOUS SPENDING CATEGORIES IN RESPONSE TO DIFFERENT INCOME TYPES.
Cultural psychology assumes that the ecocultural conditions of a particular setting shape children’s pathways, resulting in multiple adaptive solutions to universal developmental tasks. While the adaptivity of attachment and children’s psychosocial development during the early years has been thoroughly investigated, attachment research during middle childhood continues to reflect Western ideals of family. Adhering to ideas of monotropy, most studies only focus on parental attachment figures. However, this restricted empirical perspective does not only result in a Eurocentric bias, it also neglects theoretical reflections on the growing complexity of attachment during middle childhood, thus only considering a limited selection of all individuals contributing to the children’s feeling of security, even in Western settings. To investigate the variability and adaptivity of attachment during middle childhood, this study assessed children’s attachment figures in two extreme settings of development, introducing an exhaustive network perspective on attachment during this developmental stage. Children of the Cameroonian Nseh (N = 11) and German children from Bad Nauheim (N = 11) identified and differentiated all individuals contributing to their attachment need in an exploratory and transdisciplinary approach. The socio-structural composition of children’s attachment networks follows the context-specific systems of care and concepts of interconnectedness and the ecological features of each setting, resulting in marked differences between both contexts. The functional composition, however, reflects children’s preoccupation with similar developmental challenges across settings. Same-aged peers contribute to the children’s feeling of safety in both settings, thereby deviating from previous reflections on their subordinate relevance during middle childhood. Overall, these results support the adaptiveness of children’s attachment patterns while also demonstrating universal trends across contexts. They highlight the collective nature of attachment during middle childhood that exceeds the impact of individual dyads. Thus, broad and context-sensitive research strategies become a necessary addition to attachment research in order to generate an exhaustive understanding for children’s development across cultural contexts.
Using photo elicitation to introduce a network perspective on attachment during middle childhood
(2018)
In this article, we develop a child-centered network approach to attachment during middle childhood. Following monotropic ideas, current attachment research focuses on parental attachment figures despite the expansion of the children’s social environment during middle childhood, failing to generate a comprehensive and structured overview of all individuals who ensure the children’s feeling of safety. Relying on quantitative methods, these studies are also dominated by an adult perspective, limiting the children’s contributions. While there have been theoretical drafts of attachment networks during childhood, this article constitutes the first practical implementation. Using photo elicitation interviews and participant observations, we developed an innovative assessment strategy that allows children to exhaustively identify and characterize all their attachment figures on sociostructural and functional dimensions, thus positioning the children at the center of their comprehensive attachment networks that collectively contribute to their feeling of security. We combine qualitative and quantitative data to assess the children’s own understanding of their feeling of security and to locate the individual attachment figure on context-specific social dimensions, thus making the research setting, a clan in Cameroon, an inherent part of the methodological development. The data are translated into multidimensional network diagrams to visualize the children’s perception of their attachment environment and the emerging patterns of their selection. We present an exemplary network, supplementing it with observational data to discuss the ecological validity of our approach.
Bindung bildet in der Erforschung langfristiger psychosozialer Entwicklung ein zentrales Konstrukt. In Bezug auf die Phase der mittleren Kindheit liegt dabei jedoch oft eine eingeschränkte Forschungsperspektive vor: dem Konzept der Monotropie folgend, wird trotz des wachsenden sozialen Umfelds allein Eltern eine besondere Aufmerksamkeit in ihrer Rolle als Bindungsfiguren zugeordnet. Zudem fehlen Studien jenseits westlich-europäischer Entwicklungsverläufe. Ziel der vorliegenden Arbeit ist die explorative Erforschung der transkulturellen Spannbreite und der kontextspezifischen Adaptivität in der Auswahl und Funktionalität von Bindungsfiguren der mittleren Kindheit. Dazu werden Daten in zwei ökokulturell gegensätzlichen Settings erhoben, um kontextspezifische und globale Trends betrachten zu können.
Zunächst erfolgt eine ethnologische Annäherung an die frühste Kindheit im kamerunischen Setting der Nseh entlang des Tragetuchs als zentralem Care-Objekt. Diese offenbart eine symbiotische Beziehungsgestaltung, aber auch strenge Regeln des Aufbaus und der Abgrenzung im geteilten Care-System.
Anschließend wird eine methodische Strategie zur Erforschung der mittleren Kindheit entwickelt, die eine Netzwerkperspektive beinhaltet und der kindlichen Wahrnehmung folgt. Dabei werden teilnehmende Beobachtungen mit Photo Elicitation Interviews verbunden, um das vollständige Kollektiv der Bindungsfiguren zu identifizieren und in ihren soziostrukturellen und funktionellen Eigenschaften zu charakterisieren. Indem das Setting zum inhärenten Teil der Datenerhebung wird, werden dabei adaptive Prozesse zugänglich.
In Umsetzungen dieser kontextualisierend explorativen Strategie bei den kamerunischen Nseh und im deutschen Bad Nauheim werden die Bindungsnetzwerke der mittleren Kindheit erfasst und in ihrer Adaptivität diskutiert. Der Kontrastvergleich offenbart, dass die Kinder der Nseh im Vergleich zu den Kindern aus Bad Nauheim in der Altersstruktur vielfältigere, räumlich enger begrenzte und zeitlich stabilere Netzwerke beschreiben. In beiden Settings identifizieren die Kinder eine Aufteilung der inhaltlich-funktionelle Verantwortlichkeiten, die bei den Nseh gemäß den Altersgruppen verläuft.
Insgesamt zeichnet sich für die mittlere Kindheit ein komplexes Bindungsumfeld ab. Dabei verbinden sich settingspezifische Kindheitsbedingungen mit globalen Entwicklungsthemen. Das mehrdimensionale kindliche Sicherheitsgefühl kann auf die Wirkung eines Kollektivs an Bindungsfiguren zurückgeführt werden, zu dem kontextunabhängig in einem bedeutsamen Ausmaß auch Peers gehören.
It is shown that the description of a relativistic fluid at local thermodynamic equilibrium depends on the particular quantum stress-energy tensor operator chosen, e.g., the canonical or symmetrized Belinfante stress-energy tensor. We argue that the Belinfante tensor is not appropriate to describe a relativistic fluid whose macroscopic polarization relaxes slowly to thermodynamic equilibrium and that a spin tensor, like the canonical spin tensor, is required. As a consequence, the description of a polarized relativistic fluid involves an extension of relativistic hydrodynamics including a new antisymmetric rank-two tensor as a dynamical field. We show that the canonical and Belinfante tensors lead to different predictions for measurable quantities such as spectrum and polarization of particles produced in relativistic heavy-ion collisions.
The aim of this study is to trace back the translator of "Reinhold Lubenau Seyahatnamesi [Osmanlı Ülkesinde, 1587-1589]" and focus on her translation approach through paratexts. The traveller portrays the Muslim 'other' whom he met in the Ottoman Empire where he spent his time between the years 1587-1589, when the Ottoman Empire had the power and Islam was being perceived as a threat to them versus his own culture which he belonged to as a Prussian Protestant. The translation of this itinerary is available to Turkish readers after approximately 400 years in 2012. What makes this translation interesting is the translation of a source text, in which the target culture was being portrayed from the perspective of the 'other', into a target language. How was this 'foreign' perspective constructed by the traveler translated and reflected in the paratext? What was the approach of the translator against the challenges he encountered during the translation process? Answers to these questions among many others were being searched through an examination of paratexts. In addition, it was also discussed whether the author moved to the reader or the reader moved to the author. Paratexts encourage reading and direct the reception (Genette 2016). In this study, book covers, names, titles, genre, graphics illustration and footnotes were examined. Translator footnotes, which were provided by the translator in order to make the text clear, were classified in order to underline the functions of these footnotes. Translator footnotes are the tools, which make translators visible and help them to raise their voices in the texts. In peritexts, translator can provide extra information to the readers, explain and justify his/her translation decisions.
This paper traces the military role of Tibnīn and its rulers in the Latin East against the Muslims until 1187/ 583. Tibnīn played a key role in overcoming the Muslims in Tyre and controlled it in 1124. It also played a vital role in the conflict between Damascus and the Kingdom of Jerusalem. Tibnīn participated in defending Antioch, Banyas, Hebron and Transjordan several times. Furthermore, its soldiers and Knights joined the army of the Kingdom of Jerusalem to capture Ascalon in 1153, and joined the campaigns of Amaury I, King of Jerusalem, against Egypt from 1164 to1169. The military situation of Tibnīn under the rule of the royal house until its fall to the Muslims in 1187/ 583 will be studied as well
Rolf Schneider gehörte zu jenen DDR-Schriftstellern, deren Romane um 1970 überwiegend in der Bundesrepublik herauskamen. Auch war er Teil der Gruppe von Autoren, die von 1978 bis 1981 langfristige Visa erhielten und zwischen Ost- und Westdeutschland hin- und herpendelten. Es ist anzunehmen, dass der Umstand, gleichsam zwischen den Stühlen zu sitzen, Schneiders Autorschaft in hohem Maß bedingte. Damit ist zugleich die Frage aufgeworfen, in welcher Weise dies der Fall war. Im Beitrag soll dem anhand der 1965 erschienenen Erzählung Metamorphosen nachgegangen werden. Sie bietet sich hier deshalb als Textgrundlage an, da sie eine intertextuelle Relation zu Die Verwandlung von Franz Kafka aufweist, dessen Werk von den Kulturfunktionären der DDR bis in die 70er Jahre hinein abgelehnt und aus dem offiziellen "Erbe"-Kanon ausgeschlossen wurde. Vor diesem Hintergrund ist davon auszugehen, dass die in Metamorphosen enthaltenen Anspielungen auf den Kafka-Text Schneider zur Inszenierung seiner regimekritischen Autorschaft dienten. Wie dies im Einzelnen aussah, ist Gegenstand der Untersuchung, die sich den intertextuellen Bezügen von verschiedenen Seiten annähern wird, um so die Aspekte zu beleuchten, die für die literarische Selbstdarstellung Schneiders maßgeblich sind.
Nach der Befreiung des Konzentrationslagers Theresienstadt am 9. Mai 1945 fand die dort seit Februar inhaftierte Journalistin Eva Noack-Mosse eine kleine Anzahl von Gedichten und Gedichtfragmenten auf "Fetzen armseligen Papiers [...] meist mit Bleistift gekritzelt, vielfach durchgestrichen und verbessert, oft verlöscht und schwer lesbar." Sie wurden der dort am 19. April 1945 verstorbenen Kunsthistorikerin und Dichterin Gertrud Kantorowicz zugeschrieben und gehörten zu der "unübersehbaren Flut" von Versen, die sich laut Hans Günther Adlers monumentaler Geschichte von Theresienstadt über das Lager ergoss. Er sah in den meisten nur "ein einsames Gesellschaftsspiel mit sich selbst," denn noch "ein klapperndes Versmaß verspricht mehr Schutz und Bestand als das Fristen eines zerhämmerten und gnadenlosen Daseins." Geht man aber von der persönlichen Bekanntschaft der jungen Gertrud Kantorowicz mit Stefan George und den hiermit verbundenen lange nachwirkenden Anregungen aus und wird ferner berücksichtigt, welche Rolle im George-Kreis die Antike-Rezeption gespielt hat, so ist es nicht mehr so verwunderlich, dass die meisten Theresienstadt-Gedichte Kantorowicz' in antikisierenden Versformen und im hohen Stil gehalten sind; das ist nicht nur eine unerhörte Verfremdung der herabziehenden und demütigenden Lagererfahrung, sondern auch ein Sich-Erheben über Schmutz, Gewalt und Ungeist, eine ganz persönlich geprägte poetische Selbstbehauptung und Widerstandshandlung. Diesen Zusammenhängen soll im Folgenden nachgegangen werden.
This paper presents a contrastive analysis of auto- and hetero-stereotypes of Bosnians and Germans. The analysis is based on data collected from respondents choosing from a list of 140 characteristics. The anonymous online questionnaire asked respondents to identify those characteristics that they considered to be connected with their own culture or with the other culture, and to give their reasons for their choice (in the case of the most important characteristics). The analysis based on this data reveals how Germans and Bosnians perceive themselves and each other. It also enables the compilation of a list of stereotypes based on the most frequently identified characteristics, which can be used as a basis for further analysis and interpretation. This first analysis is intended as a foundation for future analyses of ethnic stereotypes among Germans and ethnic groups in the western Balkans: Bosnians, Serbs and Croats.
Game Plan
(2018)
Atrial septostomy (AS) is recommended for pulmonary arterial hypertension (PAH)-associated right ventricular (RV) failure, recurrent syncope, or pulmonary hypertensive crisis (PHC). We aimed to evaluate the feasibility and efficacy of AS to manage PAH from infancy to adulthood. From June 2009 to December 2016, transcatheter atrial communications were created in 11 PAH patients (4 girls/women; median age = 4.3 years; range = 33 days–26 years; median body weight = 14 kg; range = 3–71 kg; NYHA-/Ross class IV; n = 11). PAH was classified as idiopathic (n = 6) or secondary (n = 5). History of syncope was dominant (n = 6); two with patent foramen ovale (PFO) admitted with recurrent PHC, three patients required resuscitation before AS. Three patients had PAH-associated low cardiac output. The average pulmonary arterial pressures (PAP systolic/diastolic) were 101/50 (±34/23); the corresponding systemic arterial pressures (SAP) were 99/54 (±23/11); and the mean ratio of PAPd / SAPd was 0.97 (±0.4). Percutaneous trans-septal puncture was uneventfully performed in nine patients; a PFO was dilated in two patients. There was no procedure-related mortality. The median balloon size was 10 mm (range = 6–14 mm); the mean catheter time was 174.6 ± 48 min; fluoroscopy time was 19.8 (±11) min. Syncope and PHC were successfully treated in all patients. The mean arterial oxygen saturation decreased from 97 ± 2 to 89 ± 11.7. One patient died awaiting lung transplantation, one continues to be listed; two patients received a reverse Potts-shunt, one patient died during follow-up; seven patients are stable with PAH-specific treatment. Percutaneous AS is an effective method palliating PAH-associated syncope, PHCs or right (bi-) ventricular heart failure.
Many cancers have the tumor suppressor p53 inactivated by mutation, making reactivation of mutant p53 with small molecules a promising strategy for the development of novel anticancer therapeutics. The oncogenic p53 mutation Y220C, which accounts for approximately 100,000 cancer cases per year, creates an extended surface crevice in the DNA-binding domain, which destabilizes p53 and causes denaturation and aggregation. Here, we describe the structure-guided design of a novel class of small-molecule Y220C stabilizers and the challenging synthetic routes developed in the process. The synthesized chemical probe MB710, an aminobenzothiazole derivative, binds tightly to the Y220C pocket and stabilizes p53-Y220C in vitro. MB725, an ethylamide analogue of MB710, induced selective viability reduction in several p53-Y220C cancer cell lines while being well tolerated in control cell lines. Reduction of viability correlated with increased and selective transcription of p53 target genes such as BTG2, p21, PUMA, FAS, TNF, and TNFRSF10B, which promote apoptosis and cell cycle arrest, suggesting compound-mediated transcriptional activation of the Y220C mutant. Our data provide a framework for the development of a class of potent, non-toxic compounds for reactivating the Y220C mutant in anticancer therapy.
During the Late Cretaceous and early Cenozoic the Earth experienced prolonged climatic cooling most likely caused by decreasing volcanic activity and atmospheric CO2 levels. However, the causes and mechanisms of subsequent major global warming culminating in the late Paleocene to Eocene greenhouse climate remain enigmatic. We present deep and intermediate water Nd-isotope records from the North and South Atlantic to decipher the control of the opening Atlantic Ocean on ocean circulation and its linkages to the evolution of global climate. The marked convergence of Nd-isotope signatures 59 million years ago indicates a major intensification of deep-water exchange between the North and South Atlantic, which coincided with the turning point of deep-water temperatures towards early Paleogene warming. We propose that this intensification of Atlantic overturning circulation in concert with increased atmospheric CO2 from continental rifting marked a climatic tipping point contributing to a more efficient distribution of heat over the planet.
Analyses of scope reconstruction typically fall into two competing approaches: 'semantic reconstruction', which derives non-surface scope using semantic mechanisms, and 'syntactic reconstruction', which derives it by positing additional syntactic representations at the level of Logical Form. Grosu and Krifka (2007) proposed a semantic-reconstruction analysis for relative clauses like the gifted mathematician that Dan claims he is, in which the relative head NP can be interpreted in the scope of a lower intensional quantifier. Their analysis relies on type-shifting the relative head into a predicate of functions. We develop an alternative analysis for such relative clauses that replaces type-shifting with syntactic reconstruction. The competing analyses diverge in their predictions regarding scope possibilities in head-external relative clauses. We use Hebrew resumptive pronouns, which disambiguate a relative clause in favor of the head-external structure, to show that the prediction of syntactic reconstruction is correct. This result suggests that certain type-shifting operations are not made available by Universal Grammar.
According to Ogihara (1995), the usage of the embedded present in a speech report such as John said that Mary is in the room is restricted by the cause of John’s belief (the state that made John think that Mary is in the room): the present tense can be used only if this cause still holds at the time that John said that Mary is in the room is uttered.
This paper presents experimental evidence demonstrating that this is only one of the factors that licenses a felicitous usage of the embedded present tense. In particular, we show that the cause of belief still holding is not a necessary condition, and identify two additional, sufficient (but not necessary) factors: in cases of false belief, who is aware of the falsity of the belief and duration of the reported state. While these factors are independent, they collectively support the idea that the present tense encodes ‘current relevance’, even in embedded contexts (e.g. Costa 1972; McGilvray 1974). This gives rise to the question of how we can derive ‘current relevance’ and, in particular, whether previous analyses of the embedded present tense are adequately equipped to do so.
Zielsetzung: Beteiligung von Medizinstudierenden im Rahmen der konzeptionellen Entwicklung eines zielgruppenspezifischen und attraktiven allgemeinmedizinischen Lehrangebots im ländlichen Raum.
Methodik: Es wurde ein Fragebogen entwickelt, der die Bewertung der Studierenden hinsichtlich des aktuellen Ablaufs ihres Studiums, den späteren Berufswunsch sowie die Anforderungen an ein zu entwickelndes allgemeinmedizinisches Schwerpunktprogramm im ländlichen Raum erfasst. Mittels einer Online-Befragung wurden im Sommer 2015 alle Medizinstudierende ab dem vierten vorklinischen Semester (n=2.150) der Goethe-Universität Frankfurt einmalig befragt. Die statistische Auswertung erfolgte primär deskriptiv. Die persönliche Einstellung hinsichtlich der Bereitschaft, als Hausarzt tätig zu werden, wurde auf statistische Signifikanz überprüft. Zudem wurde erhoben, ob ein messbarer Zusammenhang zwischen der eigenen Herkunft und dem späteren Wunscharbeitsort besteht.
Ergebnisse: Von insgesamt 2.150 kontaktierten Studierenden nahmen 617 an der Befragung teil (Rücklaufquote=28,7%). Die Ergebnisse repräsentieren eine große Bandbreite an Ideen und Anregungen, die sowohl die Meinung von Befürwortern als auch eher kritisch gegenüber der Lehre in der Allgemeinmedizin eingestellten Medizinstudierenden widerspiegeln. Von dem geplanten Schwerpunktprogramm erwarten die Studierenden einen starken Praxisbezug ebenso wie das Kennenlernen administrativer sowie wirtschaftlicher Hintergründe zum Führen einer Praxis.
Schlussfolgerungen: Durch die Einbeziehung der Zielgruppe am Entwicklungsprozess bestand die Möglichkeit, das zu entwickelnde Schwerpunktprogramm auf die späteren Teilnehmer passgenauer zuzuschneiden. Zudem ist zu erwarten, dass die Beteiligung der Studierenden zu einer höheren Akzeptanz des Programms führt. Die gewonnenen Ergebnisse zur Gestaltung eines Lehrangebots können als Orientierung für die mögliche Entwicklung ähnlicher Schwerpunktprogramme an anderen medizinischen Fakultäten dienen.
Aim: Participation of medical students in the conceptual development of targeted and attractive teaching content for rural areas.
Method: A questionnaire was developed to gather information on students' views of their current medical studies, career interests, and what requirements should be met by an optional rural health program in general practice. By means of an online survey in summer 2015, all medical students from the fourth preclinical semester onwards (n=2,150) at Goethe University Frankfurt were surveyed on one occasion. Statistical analysis was mainly descriptive. Personal attitudes towards a career as a family practitioner were examined for statistical significance. Further information was gathered on whether a measurable correlation exists between personal background and desired work location.
Results: Of the 2,150 students that were contacted, 617 participated in the survey (response rate=28.7%). The results covered a wide range of ideas and recommendations and were representative both of medical students with a positive attitude toward general practice, as well as those that were rather critical of teaching in general practice. The students expected the planned health program to be of strong practical relevance and to acquaint them with the administrative and economic aspects of running a practice.
Conclusions: By including the target group in the development process, it was possible to tailor the health program to meet the needs of future participants more precisely. Student participation can also be expected to result in greater acceptance of the program. The results on teaching content may also provide other medical faculties with orientation when developing comparable programs.
The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.
We present an abundance-based checklist of Pennsylvania planthoppers (Hemiptera: Auchenorrhyncha: Fulgoroidea) compiled from available literature and 13,718 specimens. A substantial portion of the latter were bycatch from Lindgren funnel and panel traps intended to intercept wood-boring beetle species, and a directed survey for the spotted lanternfly (Lycorma delicatula (White)). The known planthopper fauna of Pennsylvania consists of 10 families, 54 genera and 139 species including 34 new state species records (and 12 new genera). In an attempt to assess the level of completeness of this survey, we compiled an abundance-based checklist of planthopper species found in states adjacent to Pennsylvania and found similar numbers of planthopper species for each state (viz. Delaware 138 species, Maryland 147, New Jersey 145, New York 162 and Ohio 126), but the cumulative species list is comprised of 240 planthopper species, suggesting that the inventory for Pennsylvania and all adjacent states may be substantially incomplete.
Rhagoletis cerasi (Linnaeus) (Diptera: Tephritidae) is reported from Mississauga, Ontario, Canada, and Niagara County, New York, United States for the first time, new records. Specimens from Ontario were collected in 2016, and New York in 2017. This fly is subject to regulatory control and poses a risk to cherry and honeysuckle in North America.
The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable (MPN-U); of note, mastocytosis is no longer classified under the MPN category. In the current review, we focus on the diagnostic criteria for JAK2/CALR/MPL mutation-related MPNs: PV, ET, and PMF. In this regard, the 2016 changes were aimed at facilitating the distinction between masked PV and JAK2-mutated ET and between prefibrotic/early and overtly fibrotic PMF. In the current communication, we (i) provide practically useful resource tables and graphs on the new diagnostic criteria including outcome, (ii) elaborate on the rationale for the 2016 changes, (iii) discuss the complementary role of mutation screening, (iv) address ongoing controversies and propose solutions, (v) attend to the challenges of applying WHO criteria in routine clinical practice, and (vi) outline future directions from the perspectives of the clinical pathologist.
Auswirkung der Chemisorption von Organothiolaten auf den elektrischen Widerstand dünner Goldfilme
(2018)
Hochgeordnete Monolagen von Organothiolaten auf Goldoberflächen bilden sich bei Kontakt einer Goldoberfläche mit einer Lösung eines Thiols oder Thioacetats spontan aus. Die Adsorption auf dünnen Metallfilmen mit Schichtdicken im Bereich von 25 - 100 nm führt zu einer Änderung des elektrischen Widerstandes des Films, die an Goldfilmen mit Schichtdicken von 25 - 40 nm über eine einfache Zweipunktmessung verfolgt wurde. Die Proportionalität der Widerstandsänderung mit der Menge an adsorbiertem Material konnte für die in dieser Arbeit verwendeten Dünnschichtsensoren bestätigt werden. Zu diesem Zweck wurden gleichzeitig Widerstands- und Oberflächenplasmonenresonanzmessungen an 40 nm starken Goldfilmen durchgeführt. In diesen Experimenten zeigt sich die Widerstandsmessung zur Beobachtung der Adsorptionskinetik als die überlegene Technologie.
Die durch Mikrokontaktdrucken und Freiätzen der gedruckten Strukturen hergestellten Sensoren zeigen eine individuelle Signalintensität. Die Normierung auf die maximale, durch Belegung mit Hexadecanthiol (HDT) oder Dodecanthiol erreichte, Signalstärke ermöglichte den Vergleich der maximalen Signalstärke von Thiolatmonolagen, die durch Belegung mit n-Alkanthiolen (CH_3(CH_2)_(n-1)-SH mit n = 12, 16, 19, 22 und 33, Cn), 11-Mercaptoundecyl-hexaethylenglycol (HSC11EG6OH), Adamantan-1-thiol (AdaSH), Triptycenthiol (TrpSH), Anthracen-2-thiol (Ant-0SH), Anthracen-2-alkanthiolen (Ant-(CH_2)_n-SH mit n = 1 - 5 und 10, Ant-nSH), p-Terphenyl-4-thiol (TP0SH), p-Terphenyl-4-alkanthiolen (TP-(CH_2)_n-SH mit n = 1 - 4, TPnSH) und p-Terphenyl-4-ethanthioacetat (TP2SAc) erzeugt wurden. Die Größe der Widerstandsänderung zeigt eine deutliche Abhängigkeit vom organischen Rest des Oberflächenadsorbats. Für die Verstärkung des Signals wurde die folgende Reihenfolge gefunden: Trp > Ada > Ant-0 > Ant-1 > TP0 > TP1 > Ant-2 > TP2 > Cn (n = 12 - 33) = C11EG6OH = Ant-n (n = 3 - 11) = TPn (n = 3, 4). Bei bekannter Verstärkung des Signals durch ein Adsorbat kann unabhängig von der Oberflächenrauigkeit die Oberflächenbedeckung durch Chemisorbate in einer Güte bestimmt werden, die der durch STM- und TEM-Messungen erreichten vergleichbar ist. Die Methode wurde angewendet, um Schichten von TP2SH und TP2SAc, die bei 20 und 60 °C aus ethanolischer Lösung abgeschieden wurden, zu vergleichen. Die Unterschiede in der Oberflächendichte, die durch eine Erhöhung der Abscheidungstemperatur zu beobachten sind, können durch eine Beschleunigung der Reaktion nach Arrhenius erklärt werden. Auch die Temperaturabhängigkeit der Abscheidungsgeschwindigkeit von HDT aus ethanolischer Lösung an Goldoberflächen, die in einem Bereich von -10 °C bis +30 °C betrachtet wurde, ist mit dem Arrhenius'schen Ansatz konform. Die Aktivierungsenergie der Adsorption von HDT auf Gold wurde auf E_a = 23 +-6 kJ/mol bestimmt.
Die Konzentrationsabhängigkeit der Abscheidung aus ethanolischer Lösung an Goldoberflächen wurde für HDT, AdaSH, TP2SH und TP2SAc untersucht. Um eine Präadsorption der Thiole vor dem eigentlichen Start der Messung zu verhindern, wurde eine Apparatur mit einem Diaphragma aus Aluminium entwickelt, das beim Start der Messung mit dem Sensor durchstoßen wird. Mit Ausnahme von TP2SH zeigen alle Adsorptive ein Adsorptions-Desorptions-Gleichgewicht. Die Adsorptionsisothermen bei 20 °C lassen sich am besten durch die Freundlich-Isotherme beschreiben. Während die Reaktionsordnung im Adsorbat für die Adsorption der Thiole nahe an 1 liegt, hat sie für die Adsorption von TP2SAc einen Wert von ca. 1/4. Damit ergibt sich für die Geschwindigkeitskonstante der Adsorption k_a(HDT) = (2,3 +-0,2) 10^4 L/(mol s), k_a(AdaSH) = (6,1 +-0,2) 10^4 L/(mol s), k_a(TP2SH) = (7,3 +-0,4) 10^3 L/(mol s) und k_a(TP2SAc) = (8 +-3) 10^-2 L^(1/4)/(mol^(1/4) s). Die Adsorptionskurven der Thiole weisen bei Konzentrationen unterhalb von 5 10^-5 mol/L einen linearen Bereich auf, der einer zwischenzeitlichen Diffusionskontrolle zugeordnet wird.
An die aufgenommenen Adsorptionskurven der Thiole wurden literaturbekannte Modelle numerisch angepasst und teilweise weiterentwickelt. Die Anpassung konnte durch die Einführung einer vor der Oberfläche gelagerten Diffusionsgrenzschicht, in welcher der zeitabhängige Verlauf der Analytkonzentration in einem System von 10 Schichten berechnet wurde, deutlich verbessert werden. Von allen getesteten Modellen zeigt nur die Adsorption mit Ausschlussmuster keine Konzentrationsabhängigkeit der Geschwindigkeitskonstante der Desorption. Dieses Modell bezieht den Verlust von Adsorptionsplätzen mit ein, die einem besetzten Adsorptionsplatz benachbart sind und durch das adsorbierte Teilchen verdeckt werden. Der daraus resultierende Zusammenhang zwischen der Konzentration freier Adsorptionsplätze und dem Bedeckungsgrad der Oberfläche Theta_F(Theta) ist abhängig vom Verhältnis der Stoßfrequenz zwischen den Teilchen und der Oberfläche zur Platzwechselfrequenz der Teilchen auf der Oberfläche. Zur Bestimmung von Theta_F(Theta) für die numerische Anpassung der Adsorptionskurven von HDT und TP2SH wurde die Oberflächenbesetzung in einem Monte-Carlo-Verfahren für eine Konzentrationsreihe in Zehnerpotenzschritten simuliert.
We examine how a firms' investment behavior affects the investment of a neighboring firm. Economic theory yields ambiguous predictions regarding the direction of firm peer effects and consistent with earlier work, we find that firms display similar investment behavior within an area using OLS analysis. Exploiting time-variation in the rise of U.S. states' corporate income taxes and utilizing heterogeneity in firms' exposure to increases in corporate income tax rates, we identify the causal impact of local firms' investments. Using this as an instrumental variable in a 2SLS estimation, we find that an increases in local firms' investment reduces the investment of a local peer firm. This effect is more pronounced if local competition among firms is stronger and supports theories that firm investments are strategic substitutes due to competition.
Delayed-onset muscle soreness (DOMS) is a common symptom in people participating in exercise, sport, or recreational physical activities. Several remedies have been proposed to prevent and alleviate DOMS. In 2008 and 2015, two studies have been conducted to investigate the effects of acupuncture on symptoms and muscle function in eccentric exercise-induced DOMS of the biceps brachii muscle. In 2008 a prospective, randomized, controlled, observer and subject-blinded trial was undertaken with 22 healthy subjects (22–30 years; 12 females) being randomly assigned to three treatment groups: real acupuncture (deep needling at classic acupuncture points and tender points; n = 7), sham-acupuncture (superficial needling at non-acupuncture points; n = 8), and control (n = 7). In 2015, a five-arm randomized controlled study was conducted with 60 subjects (22 females, 23.6 ± 2.8 years). Participants were randomly allocated to needle, laser, sham needle, sham laser acupuncture, and no intervention.
In both cases treatment was applied immediately, 24 and 48 hours after DOMS induction.
The outcome measures included pain perception (visual analogue scale; VAS), mechanical pain threshold (MPT), maximum isometric voluntary force (MIVF) and pressure pain threshold (PPT).
Results: In 2008, following nonparametric testing, there were no significant differences between groups in outcome measures at baseline. After 72 hours, pain perception (VAS) was significantly lower in the acupuncture group compared to the sham acupuncture and control subjects. However, the mean MPT and MIVF scores were not significantly different between groups. This lead to the conclusion, that acupuncture seemed to have no effects on MPT and muscle function, but reduced perceived pain arising from exercise-induced DOMS.
The more recent results from 2015 indicated that neither verum nor sham interventions significantly improved outcomes within 72 hours when compared with the no treatment control (P > 0.05).
Cell–matrix adhesion and cell migration are physiologically important processes that also play a major role in cancer spreading. In cultured cells, matrix adhesion depends on integrin-containing contacts such as focal adhesions. Flotillin-1 and flotillin-2 are frequently overexpressed in cancers and are associated with poor survival. Our previous studies have revealed a role for flotillin-2 in cell–matrix adhesion and in the regulation of the actin cytoskeleton. We here show that flotillins are important for cell migration in a wound healing assay and influence the morphology and dynamics of focal adhesions. Furthermore, anchorage-independent growth in soft agar is enhanced by flotillins. In the absence of flotillins, especially flotillin-2, phosphorylation of focal adhesion kinase and extracellularly regulated kinase is diminished. Flotillins interact with α-actinin, a major regulator of focal adhesion dynamics. These findings are important for understanding the molecular mechanisms of how flotillin overexpression in cancers may affect cell migration and, especially, enhance metastasis formation.
Background: Definite diagnosis and therapeutic management of cholangiocarcinoma (CCA) remains a challenge. The aim of the current study was to investigate feasibility and potential impact on clinical management of targeted sequencing of intraductal biopsies.
Methods: Intraductal biopsies with suspicious findings from 16 patients with CCA in later clinical course were analyzed with targeted sequencing including tumor and control benign tissue (n = 55 samples). A CCA-specific sequencing panel containing 41 genes was designed and a dual strand targeted enrichment was applied.
Results: Sequencing was successfully performed for all samples. In total, 79 mutations were identified and a mean of 1.7 mutations per tumor sample (range 0–4) as well as 2.3 per biopsy (0–6) were detected and potentially therapeutically relevant genes were identified in 6/16 cases. In 14/18 (78%) biopsies with dysplasia or inconclusive findings at least one mutation was detected. The majority of mutations were found in both surgical specimen and biopsy (68%), while 28% were only present in biopsies in contrast to 4% being only present in the surgical tumor specimen.
Conclusion: Targeted sequencing from intraductal biopsies is feasible and potentially improves the diagnostic yield. A profound genetic heterogeneity in biliary dysplasia needs to be considered in clinical management and warrants further investigation.
Translational impact: The current study is the first to demonstrate the feasibility of sequencing of intraductal biopsies which holds the potential to impact diagnostic and therapeutical management of patients with biliary dysplasia and neoplasia.
Background: There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients and methods: Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10 mg/kg by intravenous infusion every 2 weeks or physician’s choice of chemotherapy (paclitaxel 80 mg/m2 on days 1, 8, and 15 or irinotecan 150 mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
Results: A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0 months; hazard ratio (HR)=1.1 [95% confidence interval (CI) 0.9–1.4]; P= 0.81} or the secondary end points of PFS [median, 1.4 versus 2.7 months; HR=1.73 (95% CI 1.4–2.2); P> 0.99] or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Conclusions: Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
Trial registration: ClinicalTrials.gov: NCT02625623.
The Luck Charm
(2018)
Tomasi Manda, an intelligent boy whose rational mind rejects belief in witchcraft, does something that causes his mother and elder brother to fear that he might be bewitched. They decide to put 'protective medicine' into his blood. But their problem is how to get Tomasi to accept the medicine, having once before failed to convince him to have such protection. However, when Tomasi passes his primary school examinations and is selected for a boarding secondary school away from home, the two approach him with the medicine disguised as a charm, something that would bring him good luck from the strangers among whom he will now be living. Tomasi initially rejects the o?er, but when, to his surprise, he sees that this causes his mother great pain, he lets her insert into his blood 'the totally useless powder.' Then certain things begin to happen to Tomasi which, unable to explain them otherwise, he can't help thinking are being caused by the potion his mother has put in his blood. Eventually he becomes convinced that he now has a potent luck charm in his body, and reaches the frightening conclusion that from now on his life will be run by this charm. What is he to do?
Sekani's Solution
(2018)
Andreya Soko manages to win the love of his college mate, Sekani Zuza, the most beautiful, most sought-after girl in college. After ?nishing college, Andreya works hard to save for Sekani's bride price from his meager salary as a primary school teacher. From the same slim salary he also struggles to ?nance the education of his younger brothers. When his parents get killed in an accident and the problems providing the bride price are further increased, Sekani steps in with an unusual solution...
The missionary work of the Seventh-day Adventist Church started in Southern Malawi in 1902, and histories of churches are usually told from that starting point. This book uses a different approach, it tells the story of Lunjika Mission (earlier called Mombera Mission) which begins in 1932, showing how the SDA Church met a new culture, that of the strongly patrilineal Ngoni and their neighbours to the North, and how it dealt with other churches that had started missionary work in that broad area up to two generations before.
Aim: To evaluate the ability of PillCamColon2 to visualize colonic segments missed by incomplete optical colonoscopy (OC) and to assess the diagnostic yield.
Methods: This prospective multicentre study included 81 patients from nine centres who underwent second-generation colon capsule endoscopy (CCE) following incomplete OC performed by an experienced gastroenterologist (> 1000 colonoscopies). Patients with stenosis were excluded. According to patient preferences, CCE was performed the following day (protocol A) after staying on clear liquids and 0.75 L Moviprep in the morning or within 30 d after new split-dose Moviprep (protocol B). Boosts consisted of 0.75 L and 0.25 L Moviprep, and phospho-soda was given as a rescue if the capsule was not excreted after seven hours.
Results: Seventy-four patients were analysed (51% of them in group A; 49% in group B). Bowel cleansing was adequate in 67% of cases, and CCE could visualize colonic segments missed by incomplete colonoscopy in 90% of patients under protocol A and 97% of patients under protocol B (P = 0.35, n.s.). Significant polyps including adenocarcinoma were detected in 24% of cases. Detection rates for all polyps and significant polyps per patient were similar in both protocols. Polyps were found predominantly in the right colon (86%) in segments that were not reached by OC. Extracolonic findings - such as reflux esophagitis, suspected Barrett esophagus, upper GI-bleeding, gastric polyps, gastric erosions and angiectasia - were detected in eight patients. PillCamColon2 capsule was retained in the ileum of one patient (1.4%) without symptoms and removed during an uneventful resection for unknown Crohn’s disease that was diagnosed as the cause of anemia, which was the indication for colonoscopy. CCE was well tolerated. One patient suffered from self-limiting vomiting after consuming the phospho-soda.
Conclusion: Second-generation CCE using a low-volume preparation is useful after incomplete OC, and it allows for the detection of additional relevant findings, but cleansing efficiency could be improved.
Background. The purpose of this systematic review was to accurately assess the procedural success of ridge preservation technique through the application of strict inclusion and exclusion criteria.
Data Sources. A methodical search of PubMed of the US National Library of Medicine and the Cochrane Central Register of Controlled Trials was conducted for applicable articles. Only randomized controlled trials comparing ridge preservation treatment with a nongrafting control, ten-subject minimum sample size, and three or more months of follow-up were included in our study.
Types of Studies Reviewed. In a screening between January 1980 and September 2017, articles meeting predetermined criteria were further examined in a qualitative data analysis. A thorough search of the databases provided 1876 articles. Of these records, 174 were assessed for eligibility through the systematic employment of inclusion and exclusion criteria.
Results. Two records were appropriate for further data analysis. One study used a mixture of a deproteinized cancellous bovine bone and porcine collagen fibers in a block form (DBB/CF), while the other study used leukocyte-platelet-rich fibrin (L-PRF). The use of DBB/CF reduced the magnitude of vertical bone resorption, yet the study showed high risk of bias. The use of L-PRF reduced the magnitude of both the horizontal and vertical crestal bone resorption; however, the low sample size created wide standard deviations between the test and control groups. Inherent weaknesses were present in both studies. Through methodical analysis of both records, the dissimilarities prevented the conduction of a meta-analysis.
Implications of Key Findings. Within the limitations of this systematic review, L-PRF reduced the magnitude of vertical and horizontal bone resorption, which places L-PRF as a potential material of choice for ridge preservation procedures. Conclusions. Within the limitations and weaknesses of both studies, the use of DBB/CF prevented the vertical crestal bone resorption while the L-PRF prevented both the horizontal and vertical crestal bone resorption. More randomized controlled clinical trials are needed to eliminate all the confounding factors, which bias the outcome of ridge preservation techniques.
Der im Alltag wie auch in medialen Darstellungen immer wieder anzutreffende Befund, dass Arbeit "irgendwie" mit der ganzen Gesellschaft zu tun habe, das heißt auch mit unserem gesamten privaten Leben, lässt sich aus einer doppelten Blickrichtung heraus sehr viel genauer beantworten als es bisher vielfach der Fall war: nämlich erstens vom Spektrum der für den komplexen Bereich der Arbeit relevanten Diskurse aus und zweitens von der medial und sprachlich erfolgenden Zusammenführung dieser Diskurse und des dabei vermittelten Wissens.
The leptonic decay of the charged pion in the presence of background magnetic fields is investigated using quenched Wilson fermions. It is demonstrated that the magnetic field opens up a new channel for this decay. The magnetic field-dependence of the decay constants for both the ordinary and the new channel is determined. Using these inputs from QCD, we calculate the total decay rate perturbatively.
Purpose: Stereotactic radiosurgery (SRS) is an established primary treatment for newly diagnosed brain metastases with high local control rates. However, data about local re-irradiation in case of local failure after SRS (re-SRS) are rare. We evaluated the feasibility, efficacy and patient selection characteristics in treating locally recurrent metastases with a second course of SRS.
Methods: We retrospectively evaluated patients with brain metastases treated with re-SRS for local tumor progression between 2011 and 2017. Patient and treatment characteristics as well as rates of tumor control, survival and toxicity were analyzed.
Results: Overall, 32 locally recurrent brain metastases in 31 patients were irradiated with re-SRS. Median age at re-SRS was 64.9 years. The primary histology was breast cancer and non-small-cellular lung cancer (NSCLC) in respectively 10 cases (31.3%), in 5 cases malignant melanoma (15.6%). In the first SRS-course 19 metastases (59.4%) and in the re-SRS-course 29 metastases (90.6%) were treated with CyberKnife® and the others with Gamma Knife. Median planning target volume (PTV) for re-SRS was 2.5 cm3 (range, 0.1–37.5 cm3) and median dose prescribed to the PTV was 19 Gy (range, 12–28 Gy) in 1–5 fractions to the median 69% isodose (range, 53–80%). The 1-year overall survival rate was 61.7% and the 1-year local control rate was 79.5%. The overall rate of radiological radio-necrosis was 16.1% and four patients (12.9%) experienced grade ≥ 3 toxicities.
Conclusions: A second course of SRS for locally recurrent brain metastases after prior local SRS appears to be feasible with acceptable toxicity and can be considered as salvage treatment option for selected patients with high performance status. Furthermore, this is the first study utilizing robotic radiosurgery for this indication, as an additional option for frameless fractionated treatment.
Gender in Fulani proverbs
(2018)
Presented paper deals with Fulani people of West Africa and with the influence of their way of life on their language. One part of the Fulani people lives nomadic pastoral live, meanwhile another part is sedentary, living in the towns. The authors of the paper pay their attention to the the gender of Fulani proverbs which reflects the way of life of Fulani people.
Myomas, also known as fibroids, are a specific characteristic of the human species. No other primates develop fibroids. At a cellular level, myomas are benign hyperplastic lesions of uterine smooth muscle cells. There are interesting theoretical concepts that link the development of myomas in humans with the highly specific process of childbirth from an upright position and the resulting need for greatly increased “expulsive” forces during labor. Myomas might be the price our species pays for our bipedal and highly intelligent existence. Myomas affect, with some variability, all ethnic groups and approximately 50% of all women during their lifetime. While some remain asymptomatic, myomas can cause significant and sometimes life-threatening uterine bleeding, pain, infertility, and, in extreme cases, ureteral obstruction and death. Traditionally, over 50% of all hysterectomies were performed for fibroids, leading to a significant healthcare burden. In this article, we review the developments of the past 20 years with regard to multiple new treatment strategies that have evolved during this time.
Ataxia telangiectasia (A-T) is a primary immunodeficiency with mutations in the gene encoding the A-T mutated (ATM) protein that interacts with immune, hematopoietic, and endocrine targets resulting in broad multi-systemic clinical manifestations with a devastating outcome. Apart from a progressive neurodegenerative disorder, A-T leads to significantly increased susceptibility to malignancies. It is a matter of discussion whether pre-emptive allogeneic hematopoietic stem cell transplantation (alloHSCT) using a reduced intensity conditioning regimen would be an option to restore immune-competence and prevent malignancy, as shown in animal models, because conventional treatment protocols of malignant diseases using radio- and/or chemotherapy have a high rate of therapy-related morbidity and mortality in these patients. We present the course of the disease, including immune reconstitution and neurological outcome following pre-emptive alloHSCT in a 4-year-old boy with A-T on a 6 year follow-up. Our manuscript provides a proof-of-concept of alloHSCT as an individual pre-emptive treatment strategy from which some A-T patients might benefit.
An ein philosophisches Fachpublikum richtete sich Blumenberg zuerst mit "Die sprachliche Wirklichkeit der Philosophie", geschrieben 1946 und veröffentlicht im Jahr darauf in der Hamburger Akademischen Rundschau. [...] Der Essay von nur vier Seiten zeugt von Blumenbergs Hadern mit allen Versuchen, die Philosophie von Grund auf neu zu errichten. Erstaunlich daran ist nun, dass Blumenberg dabei nicht als Vertreter der Phänomenologie und Anthropologie auftritt, als der er heute vor allem gelesen wird. Stattdessen erscheint er in diesem Anfangstext als Sprachtheoretiker.
Brachiopod shells are the most widely used geological archive for the reconstruction of the temperature and the oxygen isotope composition of Phanerozoic seawater. However, it is not conclusive whether brachiopods precipitate their shells in thermodynamic equilibrium. In this study, we investigated the potential impact of kinetic controls on the isotope composition of modern brachiopods by measuring the oxygen and clumped isotope compositions of their shells. Our results show that clumped and oxygen isotope compositions depart from thermodynamic equilibrium due to growth rate-induced kinetic effects. These departures are in line with incomplete hydration and hydroxylation of dissolved CO2. These findings imply that the determination of taxon-specific growth rates alongside clumped and bulk oxygen isotope analyses is essential to ensure accurate estimates of past ocean temperatures and seawater oxygen isotope compositions from brachiopods.
Mires or peat swamps have a restricted distribution in Australia and are limited to areas where hydrological inputs exceed evapotranspiration. In NSW, mires are restricted to the coast, adjacent ranges or tablelands, and along the Great Dividing Range; most are listed as threatened ecological communities under State or Commonwealth legislation. Due primarily to the relatively high rainfall and suitable geology, the Blue Mountains region includes a number of such threatened mire ecological communities. Most of these mire types are largely included within the Greater Blue Mountains World Heritage Area, although there are notable exceptions, such as the endangered Newnes Plateau Shrub Swamps.
This paper reports on a little-known group of diverse, relatively isolated and largely unprotected mires, in a relatively low rainfall area in the upper Cudgegong River catchment, east of Rylstone in the NSW Central Tablelands, and of their floristic, hydrogeomorphic and typological relationship with other mires of the Blue Mountains. They can be broadly divided into montane bogs, montane fens and hanging swamps. Particular attention is focussed on the largest and most diverse one, Rollen Creek swamp, which contains all three types. It is hoped that highlighting this hitherto unrecognised group of high conservation-value mires will contribute to their improved conservation and encourage further research into mires of eastern NSW.
In der zweiten Hälfte des 19. und am Anfang des 20. Jahrhunderts entwickelten sich in ganz Europa die sogenannten Völkerschauen, in denen populäre Unterhaltungsformen, Inszenierungspraktiken und wissenschaftliche Ansätze eng ineinandergriffen. In Deutschland spielte dabei der Hamburger Tierhändler Carl Hagenbeck eine wesentliche Rolle: Als sein Tierhandel am Anfang der 1870er Jahre in Schwierigkeiten geriet, begann er, Zurschaustellungen fremder, als "exotisch" betrachteter Menschen zu veranstalten, was ihm großen Erfolg einbrachte. Wie bereits mehrfach in der Forschung hervorgehoben, gingen die so entstandenen Völkerschauen mit bestimmten Inszenierungstechniken einher: Es ging darum, das "Exotische" – das heißt hier vor allem die am Ende des 19. Jahrhunderts ein breites Publikum faszinierende körperliche Fremdheit – anschaulich zu machen und sie zugleich in vertraute Darstellungs- und Wahrnehmungskonventionen einzubetten, um den Zuschauern das Fremde zu vermitteln. Hagenbecks Schaustellungen zeichneten sich insbesondere durch ihre genau durchdachten, auf dramatischen Strukturen und auf melodramatischen Motiven beruhenden Attraktionen aus – wie Überfall und Frauenentführung –, die es ermöglichen, Verbindungslinien zwischen Völkerschauen und Theaterkunst zu ziehen. Es lässt sich zeigen, dass die Art und Weise, wie diese "exotischen" Menschen inszeniert wurden, vom wissenschaftlichen Blick der Anthropologen sowie von der Kooperation zwischen Anthropologen und Schaustellern beeinflusst wurde. Es soll gefragt werden, inwiefern Spuren der Völkerschauen im europäischen Theater der Jahrhundertwende um 1900 aufzufinden sind: Inwieweit übten anthropologisierte Inszenierungen fremder Völker einen Einfluss auf den Retheatralisierungsprozess des Theaters aus? Inwiefern entstand das moderne Theaterverständnis aus einer Anthropologisierung des Theaters?
Challenges of FAIR phase 0
(2018)
After two-year's shutdown, the GSI accelerators plus the latest addition of storage ring CRYRING, will be back into operation in 2018 as the FAIR phase 0 with the goal to fulfill the needs of scientific community and the FAIR accelerators and detector development. Even though GSI has been well known for its operation of a variety of ion beams ranging from proton up to uranium for multi research areas such as nuclear physics, astrophysics, biophysics, material science, the upcoming beam time faces a number of challenges in re-commissioning its existing circular accelerators with brand new control system and upgrade of beam instrumentations, as well as in rising failures of dated components and systems. The cycling synchrotron SIS18 has been undergoing a set of upgrade measures for fulfilling future FAIR operation, among which many measures will also be commissioned during the upcoming beam time. This paper presents the highlights of the challenges such as re-establishing the high intensity heavy ion operation as well as parallel operation mode for serving multi users. The status of preparation including commissioning results will also be reported.
Bebilderte Multiple-Choice- (MC) Fragen sind ein integraler Bestandteil von schriftlichen Prüfungen in der Anatomie. In bebilderten MC-Fragen bezieht sich die schriftliche Frage auf verschiedene Typen von Abbildungen wie Röntgenaufnahmen, Mikrofotografien von histologischen Schnitten oder Zeichnungen von anatomischen Strukturen. Da das Hereinnehmen von Abbildungen in MC-Fragen das Abschneiden der Items beeinflussen kann, verglichen wir die Charakteristika von anatomischen Items getestet mit bebilderten und nicht bebilderten MC-Fragen in sieben Anatomieklausuren und in zwei schriftlichen Teilen des Ersten Abschnitts der Ärztlichen Prüfung (M1).
In dieser Studie verglichen wir 25 bebilderte und 163 nicht bebilderte MC-Fragen aus Anatomieklausuren und 27 bebilderte und 130 nicht bebilderte MC-Fragen aus dem schriftlichen Teil des M1 mit einem nicht parametrischen Test für ungepaarte Stichproben. Als Ergebnis waren keine signifikanten Unterschiede im Schwierigkeits- und Trennschärfeniveau zwischen bebilderten und nicht bebilderten MC-Fragen vorhanden, dasselbe ergab sich in einer nach MC-Frageformaten stratifizierten Analyse.
Wir schließen daraus, dass das bebilderte Itemformat für sich die Itemschwierigkeit nicht zu beeinflussen scheint. Die aktuellen Ergebnisse stimmen mit früheren retrospektiven Studien überein, die keine signifikanten Unterschiede zwischen Test- und Itemcharakteristika zwischen bebilderten und nicht bebilderten MC-Fragen zeigten.
Illustrated Multiple-choice questions (iMCQs) form an integral part of written tests in anatomy. In iMCQs, the written question refers to various types of figures, e. g. X-ray images, micrographs of histological sections, or drawings of anatomical structures. Since the inclusion of images in MCQs might affect item performance we compared characteristics of anatomical items tested with iMCQs and non-iMCQs in seven tests of anatomy courses and in two written parts of the first section of the German Medical Licensing Examination (M1).
In summary, we compared 25 iMCQs and 163 non-iMCQs from anatomy courses, and 27 iMCQs and 130 non-iMCQs from the written part of the M1 using a nonparametric test for unpaired samples. As a result, there were no significant differences in difficulty and discrimination levels between iMCQs and non-iMCQs, the same applied to an analysis stratified for MCQ formats.
We conclude that the illustrated item format by itself does not seem to affect item difficulty. The present results are consistent with previous retrospective studies which showed no significant differences of test or item characteristics between iMCQs and non-iMCQs.
Stem cell-based therapies require cells with a maximum regenerative capacity in order to support regeneration after tissue injury and organ failure. Optimization of this regenerative potential of mesenchymal stromal/stem cells (MSC) or their conditioned medium by in vitro preconditioning regimens are considered to be a promising strategy to improve the release of regenerative factors. In the present study, MSC were isolated from inguinal adipose tissue (mASC) from C57BL/6 mice, cultured, and characterized. Then, mASC were either preconditioned by incubation in a hypoxic environment (0.5% O2), or in normoxia in the presence of murine epidermal growth factor (EGF) or tumor necrosis factor α (TNFα) for 48 h. Protein expression was measured by a commercially available array. Selected factors were verified by PCR analysis. The expression of 83 out of 308 proteins (26.9%) assayed was found to be increased after preconditioning with TNFα, whereas the expression of 61 (19.8%) and 70 (22.7%) proteins was increased after incubation with EGF or in hypoxia, respectively. Furthermore, we showed the proliferation-promoting effects of the preconditioned culture supernatants on injured epithelial cells in vitro. Our findings indicate that each preconditioning regimen tested induced an individual expression profile with a wide variety of factors, including several growth factors and cytokines, and therefore may enhance the regenerative potential of mASC for cell-based therapies.
This paper presents three acceptability experiments investigating German verb-final clauses in order to explore possible sources of sentence complexity during human parsing. The point of departure was De Vries et al.'s (2011) generalization that sentences with three or more crossed or nested dependencies are too complex for being processed by the human parsing mechanism without difficulties. This generalization is partially based on findings from Bach et al. (1986) concerning the acceptability of complex verb clusters in German and Dutch. The first experiment tests this generalization by comparing two sentence types: (i) sentences with three nested dependencies within a single clause that contains three verbs in a complex verb cluster; (ii) sentences with four nested dependencies distributed across two embedded clauses, one center-embedded within the other, each containing a two-verb cluster. The results show that sentences with four nested dependencies are judged as acceptable as control sentences with only two nested dependencies, whereas sentences with three nested dependencies are judged as only marginally acceptable. This argues against De Vries et al.'s (2011) claim that the human parser can process no more than two nested dependencies. The results are used to refine the Verb-Cluster Complexity Hypothesis of Bader and Schmid (2009a). The second and the third experiment investigate sentences with four nested dependencies in more detail in order to explore alternative sources of sentence complexity: the number of predicted heads to be held in working memory (storage cost in terms of the Dependency Locality Theory [DLT], Gibson, 2000) and the length of the involved dependencies (integration cost in terms of the DLT). Experiment 2 investigates sentences for which storage cost and integration cost make conflicting predictions. The results show that storage cost outweighs integration cost. Experiment 3 shows that increasing integration cost in sentences with two degrees of center embedding leads to decreased acceptability. Taken together, the results argue in favor of a multifactorial account of the limitations on center embedding in natural languages.
HuR plays an important role in tumor cell survival mainly through posttranscriptional upregulation of prominent anti-apoptotic genes. In addition, HuR can inhibit the translation of pro-apoptotic factors as we could previously report for caspase-2. Here, we investigated the mechanisms of caspase-2 suppression by HuR and its contribution to chemotherapeutic drug resistance of colon carcinoma cells. In accordance with the significant drug-induced increase in cytoplasmic HuR abundance, doxorubicin and paclitaxel increased the interaction of cytoplasmic HuR with the 5ʹuntranslated region (5ʹUTR) of caspase-2 as shown by RNA pull down assay. Experiments with bicistronic reporter genes furthermore indicate the presence of an internal ribosome entry site (IRES) within the caspase-2-5ʹUTR. Luciferase activity was suppressed either by chemotherapeutic drugs or ectopic expression of HuR. IRES-driven luciferase activity was significantly increased upon siRNA-mediated knockdown of HuR implicating an inhibitory effect of HuR on caspase-2 translation which is further reinforced by chemotherapeutic drugs. Comparison of RNA-binding affinities of recombinant HuR to two fragments of the caspase-2-5ʹUTR by EMSA revealed a critical HuR-binding site residing between nucleotides 111 and 241 of caspase-2-5ʹUTR. Mapping of critical RNA binding domains within HuR revealed that a fusion of RNA recognition motif 2 (RRM2) plus the hinge region confers a full caspase-2-5ʹUTR-binding. Functionally, knockdown of HuR significantly increased the sensitivity of colon cancer cells to drug-induced apoptosis. Importantly, the apoptosis sensitizing effects by HuR knockdown were rescued after silencing of caspase-2. The negative caspase-2 regulation by HuR offers a novel therapeutic target for sensitizing colon carcinoma cells to drug-induced apoptosis.
Acetaminophen [paracetamol, N-acetyl-p-aminophenol (APAP)]-induced acute liver injury (ALI) not only remains a persistent clinical challenge but likewise stands out as well-characterized paradigmatic model of drug-induced liver damage. APAP intoxication associates with robust hepatic necroinflammation the role of which remains elusive with pathogenic but also pro-regenerative/-resolving functions being ascribed to leukocyte activation. Here, we shine a light on and put forward a unique role of the interleukin (IL)-1 family member IL-18 in experimental APAP-induced ALI. Indeed, amelioration of disease as previously observed in IL-18-deficient mice was further substantiated herein by application of the IL-18 opponent IL-18-binding protein (IL-18BPd:Fc) to wild-type mice. Data altogether emphasize crucial pathological action of this cytokine in APAP toxicity. Adding recombinant IL-22 to IL-18BPd:Fc further enhanced protection from liver injury. In contrast to IL-18, the role of prototypic pro-inflammatory IL-1 and tumor necrosis factor-α is controversially discussed with lack of effects or even protective action being repeatedly reported. A prominent detrimental function for IL-18 in APAP-induced ALI as proposed herein should relate to its pivotal role for hepatic expression of interferon-γ and Fas ligand, both of which aggravate APAP toxicity. As IL-18 serum levels increase in patients after APAP overdosing, targeting IL-18 may evolve as novel therapeutic option in those hard-to-treat patients where standard therapy with N-acetylcysteine is unsuccessful. Being a paradigmatic experimental model of ALI, current knowledge on ill-fated properties of IL-18 in APAP intoxication likewise emphasizes the potential of this cytokine to serve as therapeutic target in other entities of inflammatory liver diseases.
Gervais’ beaked whale Mesoplodon europaeus (Gervais, 1855) is restricted to the Atlantic Ocean. Although most records are from the North Atlantic, it is probably continuously distributed in deep warm waters around the equator (Mead 1989, Norman & Mead 2001). Its occurrence in West Africa is poorly known, as records are rare. It is classified as Data Deficient (Taylor et al. 2008).
Background: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
Methods: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
Results: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.
Conclusions: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.
Die hier zu besprechende Monographie "Mensch und Landschaft im südwestlichen Latium in der römischen Antike" stellt die leicht überarbeitete Fassung der Dissertation von Michael Teichmann (im Folgenden T.) dar, die er im Winter 2016/17 an der Christian-Albrechts-Universität zu Kiel am Institut für Geoarchäologie eingereicht hat. Der Phoibos Verlag strebt mit der Serie "Phoibos Humanities Series" eine Doppelstrategie an und vertreibt das Werk sowohl als gedrucktes Buch (89 €) wie auch als E-Book (59 €). Möglicherweise erklärt sich so der Verzicht auf einen Index, da das maschinenlesbare E-Book einen solchen theoretisch überflüssig macht. Da der Rezensent mit dem gedruckten Buch gearbeitet hat, fiel das Fehlen eines Indexes doch negativ ins Gewicht. ...
Was war und ist heute die Rolle der Griots im alten Afrika? Es besteht darin, über das Leben der Gemeinschaft durch die verschiedenen historischen Begebenheiten zu berichten. So begreift auch Sembene Ousmane seine Bestimmung als Filmemacher. Er soll ein "Griot der modernen Zeiten sein". Diese Rolle als Vertreter der eignen Gemeinschaft in den modernen Medien, wie z. B. dem Kino, entspricht auch Djibril Diop Mambetys Auffassung, jenes Filmemachers aus dem Senegal, der den Film als revolutionäres Vehikel begreift. Aber was wäre der afrikanische Film, fragt sich Signer, hätte man nicht Regisseure wie Idriss Ouadreogo oder die regionale Institution des FESPACO, die jährlich Preise für afrikanische Filmemacher vergibt. Dies bedeutet, dass der afrikanische Film seit der Unabhängigkeit präsenter geworden ist und versucht, selber als Vehikel realer oder fiktionaler Faktenin Afrika zu sein. So verspricht es auch der 1988 gedrehte Film Camp "Thiaroye" von Sembene Ousmane und Thierno Faty Sow, der kolonialgeschichtliche Geschehnisse in Afrika möglichst authentisch zu erzählen.
Brachyplatys subaeneus (Westwood) (Hemiptera: Plataspidae) es una especie de chinche originaria de Asia que fue reportada en 2016 por primera vez en Panamá y las Américas. Dicha especie es un organismo invasor considerado como una plaga potencial para los cultivos de guandú (Cajanus cajan (L.) Huth) y otras leguminosas. Debido a que no se había trabajado más en este chinche desde su reporte, este estudio busca generar información respecto a su distribución geográfica en el país, focalizada a lo largo de la costa Pacífica de Panamá, desde Tortí, Panamá Este, hasta la región de Chitré, provincia de Herrera. A pesar de presentar esta distribución consideramos que esta especie invasora puede tener ámbitos de distribución más amplios en Panamá, tomando en cuenta el hecho de que es una especie con una alta tasa de reproducción y colonización.
Ulrich Gerhardt : Nachruf
(2018)
Background: Bradykinin-mediated angioedema (Bk-AE) can be life-threatening and requires specific targeted therapies. Knowledge of its epidemiology may help optimize its management.
Methods: We systematically searched the medical literature to identify abstracts of interest indexed between 1948 and March, 2016. We used published national survey data on the proportion of the population treated with angiotensin-converting enzyme inhibitors (ACEI) to derive estimates of the population prevalence of ACEI-AE in the USA, Germany and France. For hereditary angioedema (C1-INH-HAE) and C1-inhibitor related acquired angioedema (C1-INH-AAE), publications had to contain original epidemiologic data collection within a defined geographical area. Hereditary angioedema with normal C1-INH was not included in the analysis due to lack of clearly defined criteria.
Results: We identified 4 relevant publications on the prevalence of ACEI-AE, 6 on the prevalence of C1-INH-HAE, and 1 on the prevalence of C1-INH-AAE. The 1st year cumulative incidence of ACEI-AE was estimated to vary between 0.12 (population-based analyses) and 0.30 (meta-analyses of clinical trials) per 100 patient-years. The population prevalence of ACEI-AE was modeled to vary between 7 and 26 in 100,000. The prevalence of C1-INH-HAE was estimated to vary between 1.1 and 1.6 per 100,000. The prevalence of C1-INH-AAE was estimated to be 0.15 per 100,000 in one epidemiological investigation of AAE in Denmark.
Conclusions: Epidemiological evidence on Bk-AE is limited to North America and Europe. ACEI-AE is more common than C1-INH-HAE (~ 10:1), which is more common than C1-INH-AAE (~ 10:1). More studies are needed to comprehensively assess the epidemiological burden of Bk-AE.
How does social class affect people’s goals in social interactions? A rank-based perspective suggests actors from higher social classes (compared to lower social classes) have more agentic and less communal goals when interacting with same class or unspecified others. Focusing on targets’ social class, an identity-based perspective suggests the reverse: Actors should more strongly endorse communal (agentic) goals toward illegitimately lower class (higher class) compared to illegitimately higher class (lower class) targets, regardless of actors’ own social class. Three preregistered experiments (N = 2,023) manipulated actor’s social class and the nature of the target (illegitimately higher/lower class, same class, unspecified) and measured participants’ goals in imagined interactions using the Circumplex Scales of Intergroup Goals. The identity-based perspective received strong support: Across studies, actors expressed stronger agentic (communal) goals toward higher class (lower class) targets. The rank-based perspective received limited support, with relatively low-class (vs. relatively high-class) actors expressing stronger communal goals toward same-class targets.
This research investigated variation in the pronunciations of three RP vowels phonemes /e/, /ɜ:/ and /ə/, among Ewe speakers of English in Ghana. It focused on variation at both individual and societal levels, investigating how social relations within these structures influenced the use of the three vowels among the speakers. In this study, social structures were seen as a system where individual members depended on one another and were linked through multiple ties. The distribution of the vowels was in respect with the social variables: age, gender and education, including dialect and social network. The study used a corpus of word-list recorded in a face-to-face interview from 96 participants selected through stratification and networking across two dialect regions: Aŋlɔ and Eveme. Using both aural and acoustic analyses, coupled with ANOVA and t-test, the study has shown that the three RP vowels exist in Ghana Eve English as independent phonemes. Each of them however has allophonic variants; /e/ has variants [e̠], [ɪ] and [ɜ:]; /ɜ:/ has [eː] and [ɜ:], while /ə/ has [ə], [ɪ], [o] and [ʌ] as its variants. The choice of the variants of /ɜ:/ and /e/ have been found to depend on speaker age, gender, and social network. But the geographical location of the speaker will largely determine how these vowels are spoken. Phonological contexts as well as speaker idiosyncrasy are also likely to condition the choice of some of these variants, however, their effects seem less important as determinant of the differences observed than those of the social factors. It is evident that age, gender and class differentiations that have been widely reported cannot be universal, they can vary from one society to another. Also though social structures as well as social relations in a speech community can play significant roles in the individual’s linguistic repertoire, the attitude of the speaker and the phonological contexts of a segment can have a huge impact on the use of that variable.
Der Beitrag beschäftigt sich mit der Quellenlage zur Organisation der Bronzemetallurgie in West-, Süd- und Nordwestböhmen. In allen Regionen kommen Belege für den Herstellungsprozess während der gesamten Bronzezeit kontinuierlich vor. In Nordwestböhmen stammt die Mehrheit der Quellen aus der Urnenfelderzeit. Hier zeigen sich der gute Zugang zu den Rohstoffvorkommen (Zinn, Kupfer) im Erzgebirge/Krušné hory und die Beziehung zu den Flüssen Elbe/Labe und Eger/Ohře. Westböhmen bildet in der Bronzezeit ein Randgebiet mit nur wenigen metallurgischen Belegen, aber mit sehr guten Bezügen zu Zinn und Kupfer (vor allem im nördlichen Teil). In Südböhmen, wo der Schwerpunkt in der Frühbronzezeit (fast keine Funde aus Ha B) liegt, lassen sich die Kommunikationswege und Verbreitung entlang der Moldau/Vltava beobachten. Die Mehrheit der Produktionsorte fügt sich in das Siedlungsnetz ein und nutzte lokale Lagerstätten. Es konnten einige potenzielle Zentralorte der Metallurgie identifiziert werden. Allgemein überwiegen die Funde aus den Flachsiedlungen gegenüber den Höhensiedlungen (vor allem in Nordwestböhmen). Es gibt folglich keine ausschließliche Beziehung der Bronzemetallurgie zu den Burgwällen, womit Vorstellungen, die Elite organisiere die Bronzemetallurgie, widerlegt werden. Die Organisation der bronzezeitlichen Metallurgie war sicher komplexer.
Although there are many dialect speakers in Bavaria, the dialect - mainly because of its non-standardized spelling - is usually not used in common print media or on nationwide television. Nevertheless, the Bavarian dialect appears on Bavarian television (BR) and in cinema films. However, the Bavarian used on television or in films is frequently not a genuine dialect; instead it is a synthetic language which resembles the German standard and merely refers to the dialect. This is mainly due to the needs of non-dialect speakers, who would definitely have comprehension problems with the genuine dialect. Furthermore, the Bavarian dialect is often used on online platforms, such as Facebook or YouTube. In these conversational situations, face-to-face communication is replaced by written texts. In the case of dialect speakers, these texts can appear as written dialect; due to the non-standardized spelling, the texts are strongly individualized.
α-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis
(2018)
Metastasis formation requires active energy production and is regulated at multiple levels by mitochondrial metabolism. The hyperactive metabolism of cancer cells supports their extreme adaptability and plasticity and facilitates resistance to common anticancer therapies. In spite the potential relevance of a metastasis metabolic control therapy, so far, limited experience is available in this direction. Here, we evaluated the effect of the recently described α-ketoglutarate dehydrogenase (KGDH) inhibitor, (S)-2-[(2,6-dichlorobenzoyl) amino] succinic acid (AA6), in an orthotopic mouse model of breast cancer 4T1 and in other human breast cancer cell lines. In all conditions, AA6 altered Krebs cycle causing intracellular α-ketoglutarate (α-KG) accumulation. Consequently, the activity of the α-KG-dependent epigenetic enzymes, including the DNA demethylation ten-eleven translocation translocation hydroxylases (TETs), was increased. In mice, AA6 injection reduced metastasis formation and increased 5hmC levels in primary tumours. Moreover, in vitro and in vivo treatment with AA6 determined an α-KG accumulation paralleled by an enhanced production of nitric oxide (NO). This epigenetically remodelled metabolic environment efficiently counteracted the initiating steps of tumour invasion inhibiting the epithelial-to-mesenchymal transition (EMT). Mechanistically, AA6 treatment could be linked to upregulation of the NO-sensitive anti-metastatic miRNA 200 family and down-modulation of EMT-associated transcription factor Zeb1 and its CtBP1 cofactor. This scenario led to a decrease of the matrix metalloproteinase 3 (MMP3) and to an impairment of 4T1 aggressiveness. Overall, our data suggest that AA6 determines an α-KG-dependent epigenetic regulation of the TET–miR200–Zeb1/CtBP1–MMP3 axis providing an anti-metastatic effect in a mouse model of breast cancer-associated metastasis.
Three Neotropical species are transferred to the genus Premnobius Eichhoff (Coleoptera: Curculionidae: Scolytinae: Ipini): Premnobius assiduus (Schedl, 1961, from Xyleborus), P. flechtmanni (Wood, 2007, from Acanthotomicus) and P. neoajunctus (Schedl, 1967, from Xyleborus). An illustrated key is presented for the native and introduced species of the genus known from the New World.
Two new species of marine Platyhelminthes, Microstomum laurae sp. nov. and Microstomum edmondi sp. nov. (Macrostomida: Microstomidae) are described from the west coast of Sweden. Microstomum laurae sp. nov. is distinguished by the following combination of characters: rounded anterior and posterior ends; presence of approximately 20 adhesive papillae on the posterior rim; paired lateral red eyespots located level with the brain; preoral gut extending anterior to brain and and very small sensory pits. Microstomum edmondi sp. nov. is a protandrous hermaphrodite with a single ovary, single testis and male copulatory organ with stylet. It is characterized by a conical pointed anterior end, a blunt posterior end with numerous adhesive papillae along the rim, and large ciliary pits. The stylet is shaped as a narrow funnel with a short, arched tip. In addition, the first records of fully mature specimens of Microstomum rubromaculatum von Graff, 1882 from Fiskebäckskil and a phylogenetic analysis of Microstomum Schmidt, 1848 based on the mitochondrial cytochrome oxidase I (COI) gene are presented.
Quasifree one-proton knockout reactions have been employed in inverse kinematics for a systematic study of the structure of stable and exotic oxygen isotopes at the R3B/LAND setup with incident beam energies in the range of 300–450 MeV/u. The oxygen isotopic chain offers a large variation of separation energies that allows for a quantitative understanding of single-particle strength with changing isospin asymmetry. Quasifree knockout reactions provide a complementary approach to intermediate-energy one-nucleon removal reactions. Inclusive cross sections for quasifree knockout reactions of the type AO(p,2p)A−1N have been determined and compared to calculations based on the eikonal reaction theory. The reduction factors for the single-particle strength with respect to the independent-particle model were obtained and compared to state-of-the-art ab initio predictions. The results do not show any significant dependence on proton-neutron asymmetry.
Wie kommen Objekte ins Museum? Wurden sie gekauft, gesammelt, geerbt oder sogar geraubt? Mit diesen grundlegenden Fragen beschäftigt sich die Provenienzforschung nicht erst seit dem aufsehenerregenden Bilderfund in München 2013, sondern sie dienen auch vier Frankfurter Museen als verbindendes Element ihres Kooperationsprojektes Gekauft. Gesammelt. Geraubt. Vom Weg der Dinge ins Museum. ...
"Eames-the architect and the painter" ist ein Dokumentarfilm über das Paar Ray und Charles Eames, der sowohl ihr Arbeits-, als auch ihr Privatleben vorstellt. Der Film erzählt über die sehr eindrucksvolle Schaffenskraft und Arbeitsweise des kreativen Paares, das in seiner Werkstatt, dem Design Office Eames, ab Mitte der 1940er Jahre vor allem eine neue, moderne Formensprachen für Möbel suchte. Ihr Hauptanliegen galt von Beginn an der seriellen Anfertigung von Stühlen und Möbeln, die den neuen Ansprüchen des nach Aufbruch strebenden Zeitgeistes gerecht werden sollten. Dementsprechend wichtig war es ihnen, einen Ort zu etablieren, in dem, fern jeglicher Dogmatik und gängiger Arbeitsweisen, experimentell und freigeistig gearbeitet werden konnte. ...
This paper presents a new account of the generalization that focused elements cannot be elided, framed within Unalternative Semantics, a framework that does away with syntactic F-marking. We propose the mirror image of the generalization: what is elided cannot introduce alternatives. We implement this as a focus restriction in UAS and then go on to show how to account for MAXELIDE effects using the same technique, without making reference to any transderivational constraints.
Von Passivität, Abneigung, gar einem "tief verwurzelte[n] Mißtrauen" gegenüber dem Interview, wie es Volkmar Hansen als typisch für Schriftstellerinnen und Schriftsteller diagnostiziert, kann im Falle Peter Kurzecks keine Rede sein. Der Autor zeigt sich in journalistischen Gesprächen deutlich engagiert, er gibt bemerkenswert ausführlich Auskunft: über den Inhalt seiner Romane, den Prozess des Schreibens und dessen Motivation; über die Erinnerung an die eigene Kindheit im hessischen Staufenberg und die Flucht aus Westböhmen dorthin; über bereits geschriebene oder noch zu schreibende Bücher, über Möglichkeiten und Grenzen der eigenen autobiographisch grundierten Erinnerungsarbeit. Wo andere mit Abneigung reagieren und ausweichen, legt Kurzeck sein Schreiben bereitwillig offen, um dabei eben nicht nur zu erläutern, worum es in den Texten seiner "Serie" inhaltlich, motivisch oder konzeptionell geht oder gehen wird, sondern auch, um dezidiert Einblicke in die eigene Dichterwerkstatt zu ermöglichen.
Wenn es die Aufgabe einer Ikonologie der Architektur ist, das Verstehen "des Bauwerks als Sinnträger" zu befördern, unter anderem also die Frage zu beantworten, was "den Menschen [...] diese oder jene Form bedeutet" hat, dann kann versuchsweise 'Monumentalität' ein Suchbegriff sein, der geeignet ist, der ikonologischen Bedeutung von Bauten näher auf die Spur zu kommen. Denn hier geht es um symbolische Aufladung, die etwas entstehen lässt, das Martin Warnke einmal "Bedeutungsarchitektur" nannte. Doch der Begriff ist belastet. Historisch galt Monumentalität in der Architektur schon nach dem Ersten Weltkrieg und den Exzessen des Historismus als obsolet; die Klassische Moderne zentrierte sich um ganz andere Begriffe wie den der Funktion. Monumentalität als Phänomen schien verschwunden, und der Funktionalismus brauchte keine Ikonologie. Nur so exotische Projekte wie das Neu-Delhi von Edwin Lutyens und später die unsäglichen Monumentalbauten der europäischen Diktaturen waren noch monumental. Doch plötzlich wurde an unerwarteter Stelle, nämlich aus dem Zentrum der modernen Bewegung selbst, deren Protagonisten im Lauf der 1930er Jahre aus politischen Gründen vielfach in die USA emigriert waren, und zudem zu einem auf den ersten Blick irritierenden Zeitpunkt die Diskussion neu eröffnet. Niemand Geringeres nämlich als Sigfried Giedion, der Chefideologe der Moderne, startete einen entsprechenden Vorstoß. Zusammen mit José Luis Sert und Fernand Léger verfasste er 1943 seine 'Nine Points on Monumentality'.
The Gleason grading system remains the most powerful prognostic predictor for patients with prostate cancer since the 1960s. Its application requires highly-trained pathologists, is tedious and yet suffers from limited inter-pathologist reproducibility, especially for the intermediate Gleason score 7. Automated annotation procedures constitute a viable solution to remedy these limitations. In this study, we present a deep learning approach for automated Gleason grading of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining. Our system was trained using detailed Gleason annotations on a discovery cohort of 641 patients and was then evaluated on an independent test cohort of 245 patients annotated by two pathologists. On the test cohort, the inter-annotator agreements between the model and each pathologist, quantified via Cohen’s quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the inter-pathologist agreement (kappa = 0.71). Furthermore, the model’s Gleason score assignments achieved pathology expert-level stratification of patients into prognostically distinct groups, on the basis of disease-specific survival data available for the test cohort. Overall, our study shows promising results regarding the applicability of deep learning-based solutions towards more objective and reproducible prostate cancer grading, especially for cases with heterogeneous Gleason patterns.
Das Ziel der vorliegenden Arbeit war es, MALDI-Massenspektrometrie als robuste Analysenmethode für die quantitative Analyse niedermolekularer Verbindungen aus komplexen biologischen Matrizes zu etablieren. Zu Beginn der Arbeit wurden drei typische Fragestellungen im Bereich der Lebensmittelanalytik, der medizinischen Forschung und der klinischen Chemie ausgewählt, um die Methodik anhand dieser Modellsysteme zielgerichtet zu entwickeln und zu bewerten. Für jede dieser Fragestellungen wird routinemäßig ein hoher Probendurchsatz verlangt und damit werden hohe Anforderungen an die Probenvorbereitung gestellt, da diese einfach, schnell, reproduzierbar, Matrix-tolerant und automatisierbar sein muss um die Weiterentwicklung zur Hochdurchsatzanalytik zu erlauben.
Der quantitative Nachweis von Melamin und seinen Derivaten wurde aufgrund des Aufkommens von Milchprodukten, die mit diesen Verbindungen kontaminiert waren, ein wichtiger Bestandteil der Analytik dieser Lebensmittel. Insbesondere an diesem Beispiel zeigte sich der Vorteil des Einsatzes von MALDI-Massenspektrometrie zur Analyse kleiner Moleküle. Aufgrund der höheren Toleranz gegenüber Puffern und Salzen konnte die Probenvorbereitungszeit der für die FDA entwickelten Methode zur Quantifizierung von Melamin in Milchpulver mittels LC-ESI von ca. 140 min auf 90 min reduziert werden, da auf die zeitaufwendige Flüssigchromatographie verzichtet werden konnte. So wurde Melamin mit einem LLOQ von 0,5 ppm quantifiziert, was unterhalb der Vorgaben der WHO (2,5 ppm in Milichpulver und 1 ppm in Babynahrung) lag. Cyanursäure, ein Derivat von Melamin welches für die Bildung schwerlöslicher Komplexe in der Niere mitverantwortlich gemacht wird, konnte ebenfalls mit der entwickelten MALDI-MS Methode quantifiziert werden. Allerdings war die ermittelte Bestimmungsgrenze mit 15 ppm um den Faktor 30 schlechter als bei Melamin. Die Nachweisgrenze bei MALDI-MS ist stark von der MALDI-Matrix abhängig und die Verwendung von Sinapinsäure war eine gute Kompromisslösung, um die Analyten in einem Spot im positiven und negativen Reflektormodus zu analysieren. Allerdings wurde diese Matrix zur Analyse von Analyten im positiven Reflektormodus entwickelt. Bislang wurden nur wenige Matrizes für MALDI-MS im negativen Reflektormodus beschrieben, um z.B. Säuren besser nachweisen zu können. Forschung in diesem Bereich wird neue Möglichkeiten zur Detektion negativ geladener kleiner Moleküle ergeben.
Des Weiteren wurden im Rahmen dieser Arbeit auch Lösungen für klinische Fragestellungen wie etwa den Nachweis von Methylphenidat im Plasma und Gehirn von Ratten oder der Dried Blood Spot Analytik entwickelt. Bei beiden Methoden wurde jeweils nur eine einfache Flüssig-Flüssig-Extraktion zur Probenvorbereitung angewendet und sie ließen sich sehr gut auf Realproben übertragen.
Methylphenidat konnte im Plasma im Konzentrationsbereich von 0,1-40 ng/mL und im Hirnhomogenat im Konzentrationsbereich von 0,4-40 ng/mL quantifiziert werden, was gut im Konzentrationsbereich der Realproben von mit Methylphenidat gefütterten Ratten lag. Dazu standen das Plasma und die Gehirne von fünf Ratten zur Verfügung. Es wurde eine lineare Korrelation zwischen der MPH-Konzentration im Gehirnhomogenat und im Plasma gefunden, was basierend auf den bis dato bekannten Literaturergebnissen ein zu erwartendes Ergebnis war, aber zukünftig mit einer größeren Anzahl von Versuchstieren verifiziert werden sollte. Während der Methodenentwicklung war auch bei diesem Projekt die Auswahl der MALDI-Matrix ausschlaggebend für den Erfolg der Messungen. Im MALDI-Massenspektrum interferierte das Signal des Natriumaddukts von CHCA mit dem Signal von MPH. Für dieses Problem kamen zwei mögliche Lösungen in Betracht. Erstens die Quantifizierung mit ClCCA als MALDI-Matrix, da hier keine Interferenzen auftraten. In ersten Vorversuchen konnte MPH so in einem Konzentrationsbereich von 1-48 ng/mL mit einer exzellenten Linearität von R2=0,9992 quantifiziert werden. Eine zweite mögliche Problemlösung war die Verwendung von Tandem-Massenspektrometrie. Hierzu wurden Fragmentionen-Massenspektren der überlagerten Signale aufgenommen. MPH und der verwendete interne Standard MPH-d9 zeigten dabei spezifische Fragmentionensignale, über die quantifiziert wurde. Da die Sensitivität um den Faktor 100 im Vergleich zu MS-Spektren von CHCA und ClCCA gesteigert werden konnte, wurde die weitere Methodenentwicklung basierend auf der Tandem-Massenspektrometrie mit der MALDI-Matrix CHCA durchgeführt. Überdies sind MS/MS-Versuche unter Verwendung von ClCCA als MALDI-Matrix für kleine Moleküle sehr erfolgsversprechend und sollten in weiteren Forschungsarbeiten durchgeführt werden.
Die Dried Blood Spot Technik als alternative Probenvorbereitung bietet eine Reihe von Vorteilen, wie etwa den einer einfacheren Lagerung und eines einfacheren Transports einer großen Menge von Proben. Darüber hinaus werden nur wenige Mikroliter Blut verwendet, was vorteilhaft ist bei z B. klinischen Studien oder dem Therapeutic Drug Monitoring. Diese Art der Probennahme ist somit eine perfekte Ergänzung für weitere quantitative Analysen von Methylphenidat in Rattenblut. Den Ratten würden nur wenige Mikroliter Blut entnommen werden, was ihr Überleben sichert und der Transport der Proben auf dem Postweg wäre wesentlich einfacher. Um eine allgemein verwendbare DBS-MALDI-MS-Methode zu entwickeln, wurden neben Methylphenidat auch bekannte Analyten aus dem Bereich des Dopings sowie Lamotrigin, Coffein und Theophyllin als Beispiele für das Therapeutic Drug Monitoring verwendet. Es wurden verschiedene Lösungsmittel zur Extraktion eingesetzt, wobei sich eine Kombination aus Methyl-tert-Butylether und Ethanol, sowie Aceton als am besten geeignet erwies. Einige Analyten wie Coffein, Theophyllin und Lamotrigin wurden bis zu einer Konzentration von 0,5 μg/mL quantifiziert. Diese Bestimmungsgrenze ist bei Analyten aus dem Bereich des Dopings wie z.B. Salbutamol, Methylphenidat oder Clenbuterol, deren therapeutisch wirksame Plasmakonzentration im Bereich von wenigen Nanogramm pro Milliliter Blut liegt, um den Faktor 15-500 zu hoch. Diese Analyten waren bis zu einer Konzentration von 5 μg/mL im Blut mittels MALDI-MS problemlos nachweisbar. Um die Sensitivität zu erhöhen, ist es allerdings sinnvoll, die Extraktion zukünftig für die einzelnen Analyten zu optimieren, sie mittels Festphasenextraktion oder LC anzureichern und MS/MS-Spektren aufzunehmen. Für die Analyten Coffein, Theophyllin und Lamotrigin, deren therapeutisch wirksame Plasmakonzentration im ein- bis zweistelligen Mikrogramm-pro-Milliliter Bereich liegt, eignete sich die entwickelte Methode sehr gut. Es wurde eine Methodenvalidierung durchgeführt, wobei die validierten Parameter den Vorgaben der FDA entsprachen.
Da die Auswahl der MALDI-Matrix bei den verschiedenen Methodenentwicklungen jeweils ein kritischer Faktor war, wurden abschließend eine Auswahl von Analyten mit einer Molekülmasse bis ca. 600 Da mit verschiedenen MALDI-Matrizes präpariert. Ein Großteil der Analyten wurde am sensitivsten mit ClCCA nachgewiesen. Im Rahmen dieser Versuche wurde auch erstmals ein Strukturanalogon von ClCCA, und zwar ClCCA-Tetrazol, als alternative MALDI-Matrix eingesetzt, bei welchem die Carboxylgruppe durch einen Tetrazolring ausgetauscht wurde. Diese zeigte eine sehr homogene Kristallisation und für einige Analyten eine bis zu Faktor 3 höhere Signalintensität im Vergleich zu ClCCA. Außerdem war auffällig, dass einige Analyten unter bestimmten Präparationsbedingungen wie z B. der Graphite Supported Preparation sensitiver mittels MALDI-MS nachweisbar waren. Bei anderen Analyten verschlechterten sich die Analysenergebnisse. Graphit verändert stark die Kristallisation der MALDI-Matrix und es wird vermutet, dass sich dies auf den Einbau der Analyten in die Matrixkristalle auswirkt. Es konnte bislang aber noch nicht abschließend geklärt werden, wie genau die Präparation der Proben Einfluss auf den Einbau der Analyten in die Matrix nimmt. Eine Untersuchung dieser Phänomene sollte daher Gegenstand weiterer Forschungsprojekte sein.
Zusammenfassend stellt die MALDI-Massenspektrometrie eine schnelle und robuste Methode zur Quantifizierung einer Vielzahl kleiner Moleküle in komplexen biologischen Matrizes dar.
Dialektik
(2018)
Was 'Dialektik' nun genau sei, darüber gibt es immer noch sehr verschiedene und auch einander ausschließende Auffassungen. Vor allem auch darüber, ob es eine Dialektik gebe oder geben könne, die sich noch besonders durch das Attribut 'materialistisch' empfehlen würde. Je näher wir hinsehen, desto mehr entschwindet uns der Begriff, der einmal so viele Gewissheiten trug. Vielleicht liegt das auch schon daran, dass sich im Begriff der Dialektik viele Bedeutungsdimensionen gleichsam sedimentiert haben; er trägt schwer an seiner Geschichte und kann sich gerade deshalb immer wieder von einseitigen Fixierungen zurückziehen.
The Trichoptera of Panama V. Descriptions of new species, new country records, and a synonymy
(2018)
The Río Chiriqui basin is one of 52 major watershed areas, or cuencas, in the Republic of Panama. It occurs in western Panama, discharges into the Pacific Ocean, and includes portions of Volcán Barú on its northern extent. The Río Caldera occupies the northernmost subbasin of this basin. Two of its tributaries, Quebrada Grande and Quebrada Jaramillo, occur in close proximity and on opposite sides, and have different recent geologic histories and current land use patterns. During the course of investigating the caddisfly fauna of these two drainages, three new species of the microcaddisfly genus Neotrichia Morton (Trichoptera: Hydroptilidae) were identified: N. collierorum and N. anzuelo from Quebrada Jaramillo and N. tatianae from Quebrada Grande. These are described and figured herein. We also add one new genus (Rhyacopsyche Mueller) and five new country records (Hydroptila paschia Mosely, Metrichia ancora Bueno-Soria and Holzenthal, Ochrotrichia jolandae BuenoSoria and Holzenthal, Rhyacopsyche obliqua Flint, and Chimarra (Curgia) maritza Flint) for Panama. Finally, we designate Ochrotrichia abrelata Harris and Armitage, 2015 as a junior synonym of Ochrotrichia jolandae Bueno-Soria and Holzenthal, 2008. This synonymy and the newly recorded species and country records increase Panama’s known trichopteran fauna to 350 species, distributed among 15 families and 52 genera.