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Brit Schwerin nimmt sich in ihrem Artikel "die bisher jedermann unbekannt gewesen [ist/war/sei/wäre] -Zum Rückgang des ersparten Finitums in Nebensätzen des frühen Neuhochdeutsch" des Phänomens der afiniten Nebensätze an, die in der Frühen Neuzeit im deutschen Sprachraum weit verbreitet waren. Ihre Analyse von Nebensätzen mit und ohne finites Verb in Texten aus dem 17. und 18. Jh. ergibt, dass der Rückgang der afiniten Konstruktionen in Verbindung mit dem Bedürfnis nach eindeutiger Markierung grammatischer Kategorien wie Tempus und Modus steht. Die diachronen Studien decken somit Sprachwandel auf verschiedenen Ebenen ab.
Wie sich Konzessivkonnektoren im 18. und 19. Jh. entwickelt haben, untersuchen Lisa Bürgerhoff, Jana Giesenschlag, Linda Kunow und Alexandra Kern für ihren Beitrag "Von ob ich schon wanderte zu obschon ich wanderte?! - Eine Korpusuntersuchung zur Konzessivität von 1700-1900". Ihre Untersuchungen im Deutschen Textarchiv zeigen unter anderem einen Zusammenhang zwischen der Zusammenschreibung der Konnektoren und einer eindeutig konzessiven Lesart, der für obschon, obgleich, obwohl und obzwar allerdings unterschiedlich stark ist. Auch die Faktizität der Teilsätze und das Auftreten verstärkender Partikeln sind für die Entwicklung der ob-Gruppe von Bedeutung. Als eindeutigste und frequenteste Konzessivkonnektoren stellen sich insgesamt obwohl und vor allem obzwar heraus.
Mit der mittelhochdeutschen Nebensilbenabschwächung beschäftigt sich Tanja Stevanovićs Beitrag "Wo sind die vollen Vokale geblieben? Eine Untersuchung möglicher Einflussfaktoren auf die Nebensilbenabschwächung". Dafür hat sie in einer Korpusuntersuchung im Referenzkorpus Mittelhochdeutsch schwache Verben analysiert, die trotz der fortschreitenden Nebensilbenabschwächung noch im Mittelhochdeutschen Vollvokale in Endsilben aufweisen.
Lena Schnee analysiert in ihrem Beitrag "Eingenordet - Morphologische Assimilation mittelniederdeutscher Lehnwörter im Altnordischen" die Liste mittelniederdeutscher Entlehnungen im Altnordischen Etymologischen Wörterbuch und zeigt, wie die mittelniederdeutschen Wörter, die in der Hansezeit in die skandinavischen Sprachen entlehnt wurden, an das Altnordische angepasst wurden. Dabei wendet sie ein Transderivationsmodell an, um die morphologische Assimilation nicht nur von ganzen Lexemen, sondern auch von Affixen und Wortstämmen nachzuvollziehen. Schnees Untersuchung ergibt, dass bei der Entlehnung in das Altnordische hauptsächlich die Affixe adaptiert wurden. Die mittelniederdeutschen Affixe wurden überwiegend durch native oder entlehnte altnordische ersetzt, was darauf hinweist, dass die Morphemgrenzen und Wortbildungselemente bei der Entlehnung als solche erkannt wurden. Als Erklärung hierfür führt Schnee die typologische Ähnlichkeit der beiden Sprachen an.
Die hier abgedruckten Beiträge sind in einem Lehrprojekt zum Thema "Wie verändern wir Sprache?" entstanden. Das im Rahmen des Universitätskollegs 2.0 aus Mitteln des BMBF geförderte Projekt fand vom Sommersemester 2017 bis zum Wintersemester 2017/18 an der Universität Hamburg statt. Insgesamt 17 Studierende beschäftigten sich über ein Jahr hinweg mit aktuellen und historischen Sprachwandelphänomenen und führten eigene empirische Forschungsprojekte durch, die sie auf der studentischen Tagung am 1.-3. Februar 2018 präsentierten. Die Beiträge beschäftigen sich aus diachroner sowie synchroner Perspektive mit Sprachvariation und -wandel.
Diyalog 2018/1
(2018)
Im Fachbereich der Deutschen Literatur äußert sich der erste Artikel zur Autorinszenierung in Rolf Schneiders Erzählung "Metamorphosen". Eine Deutung orientalischer Spuren in Hofmannsthals lyrischem Drama "Die Hochzeit der Sobeide" bildet den Schwerpunkt des zweiten Artikels dieser Rubrik. Im dritten Beitrag dieses Fachbereichs geht es um das Leben und Schreiben von Wolfgang Hilbig und die Schwierigkeiten ein Mann zu sein. Der vierte Beitrag stellt "Leutnant Gustl" als eine repräsentative Figur für die Identitätdefizite in der Gesellschaft in den Mittelpunkt. Erich Maria Remarques Roman "Im Westen nichts Neues" bildet den Ausgangspunkt für die Analyse von 'Kriegstrauma' als eine der bedeutendsten Herausforderungen in der Antikriegsliteratur, was im fünften Beitrag der Rubrik Deutsche Literatur nachgelesen werden kann. Dem Fachbereich Komparatistik sind zwei Artikel zuzuordnen. Der erste stellt anhand eines episch dekadenten Dialogs einen dekadenten Vergleich des Todes in den Werken von Tezer Kıral und Hugo von Hofmannsthal in den Mittelpunkt. Im zweiten Beitrag erfolgt eine Analyse des Romans 'Yaban' von Yakup Kadri im Sinne der Dekadenz. Sieben Beiträge bearbeiten Themen aus der Erziehungswissenschaft bzw. aus dem DaF-Bereich. Überlegungen hinsichtlich der Vermittlung von Speicherstrategien beim Lernen mit der Wortliste des Goethe-Zertifikats B1 bilden den Fokus des ersten Beitrags dieser Rubrik. Der zweite Beitrag präsentiert Ergebnisse einer Studie zur fehleranalytischen Kompetenz der Studenten/innen in der Deutschlehrerausbildung. Der dritte Artikel analysiert und bewertet Sprachlernspiele in dem Lehrwerk 'MOMENT MAL 1' und 'MOMENT MAL 2'. Der vierte Beitrag dieses Fachbereichs ist in Türkisch verfasst und stellt Überlegungen zur Entwicklung von digitalen Spielen und zu gamifizierten Anwendungen in dem Fremdsprachenunterricht in den Mittelpunkt. Ebenfalls in Türkisch verfasst ist der fünfte Aufsatz, der bei der Lehre von Türkisch als Zweitsprache Nutzen aus den Modellen und Erfahrungen thematisiert, die bei der Vermittlung von Deutsch als zweite Sprache mit in Deutschland lebendenden Migranten gemacht worden sind. Thema des sechsten Artikels ist die Erforschung von Stereotypen in DaF- und TRaF-Lehrwerken und ihr Potenzial als Störfaktor oder Impulsgeber. Der letzte Beitrag des Bereichs Erziehungswissenschaft bzw. DaF fokussiert eine korpusbasierte Studie am Beispiel der Germanistikstudenten der Ege Universität, in der die pragmatisch-diskursive Fähigkeit in den mündlichen Prüfungsgesprächen analysiert wird. Dem Bereich Translationswissenschaft sind vier Aufsätze zugehörig. In dem ersten Beitrag wird eine empirische Studie präsentiert, die die Rolle sprachlicher und kultureller Kompetenz in der "Funktionalen Übersetzung" zum Thema hat. In Türkisch verfasst ist der zweite Artikel dieser Rubrik, der Maßstäbe der Textwahl im Übersetzungsunterricht behandelt. Informationen zur Konzeption des Türkischen Übersetzerlexikons werden im dritten Aufsatz gegeben. Der in Türkisch verfasste vierte Beitrag dieses Fachbereichs gibt einen allgemeinen Überblick über ins Türkische übersetzte deutsche Literatur. Der Forum-Teil ist dem in Türkisch verfassten Beitrag vorbehalten, der mit Edmund Husserl in Bezug auf das Museum des 11. Septembers als Erinnerungszeichen die Suche nach Sinn fokussiert. In der Rubrik Berichte werden im Rückblick Informationen zu zwei Konferenzen mitgeteilt. In dem ersten Tagungsbericht wird die Stärke und Rolle der deutschen Sprache in Mitteleuropa betont, so, wie sie in einer linguistischen Konferenz vermittelt worden ist. In dem zweiten Tagungsbericht werden Erfahrungen und Informationen zum XI. Internationalen Kongress der Germanisten Rumäniens wiedergegeben. Neben den Aufsätzen und Berichten gibt es in dieser Ausgabe auch eine in Türkisch geschriebene Rezension zum Werk "Lernabenteuer Deutsch - Das Geheimnis der Himmelsscheibe".
Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, p < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG (p < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group (p < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.
A key function of reversible protein phosphorylation is to regulate protein–protein interactions, many of which involve short linear motifs (3–12 amino acids). Motif‐based interactions are difficult to capture because of their often low‐to‐moderate affinities. Here, we describe phosphomimetic proteomic peptide‐phage display, a powerful method for simultaneously finding motif‐based interaction and pinpointing phosphorylation switches. We computationally designed an oligonucleotide library encoding human C‐terminal peptides containing known or predicted Ser/Thr phosphosites and phosphomimetic variants thereof. We incorporated these oligonucleotides into a phage library and screened the PDZ (PSD‐95/Dlg/ZO‐1) domains of Scribble and DLG1 for interactions potentially enabled or disabled by ligand phosphorylation. We identified known and novel binders and characterized selected interactions through microscale thermophoresis, isothermal titration calorimetry, and NMR. We uncover site‐specific phospho‐regulation of PDZ domain interactions, provide a structural framework for how PDZ domains accomplish phosphopeptide binding, and discuss ligand phosphorylation as a switching mechanism of PDZ domain interactions. The approach is readily scalable and can be used to explore the potential phospho‐regulation of motif‐based interactions on a large scale.
Background: Ever since it was discovered that zoophilic vectors can transmit malaria, zooprophylaxis has been used to prevent the disease. However, zoopotentiation has also been observed. Thus, the presence of livestock has been widely accepted as an important variable for the prevalence and risk of malaria, but the effectiveness of zooprophylaxis remained subject to debate. This study aims to critically analyse the effects of the presence of livestock on malaria prevalence using a large dataset from Indonesia.
Methods: This study is based on data from the Indonesia Basic Health Research ("Riskesdas") cross-sectional survey of 2007 organized by the National Institute of Health Research and Development of Indonesia’s Ministry of Health. The subset of data used in the present study included 259,885 research participants who reside in the rural areas of 176 regencies throughout the 15 provinces of Indonesia where the prevalence of malaria is higher than the national average. The variable "existence of livestock" and other independent demographic, social and behavioural variables were tested as potential determinants for malaria prevalence by multivariate logistic regressions.
Results: Raising medium-sized animals in the house was a significant predictor of malaria prevalence (OR = 2.980; 95% CI 2.348–3.782, P < 0.001) when compared to keeping such animals outside of the house (OR = 1.713; 95% CI 1.515–1.937, P < 0.001). After adjusting for gender, age, access to community health facility, sewage canal condition, use of mosquito nets and insecticide-treated bed nets, the participants who raised medium-sized animals inside their homes were 2.8 times more likely to contract malaria than respondents who did not (adjusted odds ratio = 2.809; 95% CI 2.207–3.575; P < 0.001).
Conclusions: The results of this study highlight the importance of livestock for malaria transmission, suggesting that keeping livestock in the house contributes to malaria risk rather than prophylaxis in Indonesia. Livestock-based interventions should therefore play a significant role in the implementation of malaria control programmes, and focus on households with a high proportion of medium-sized animals in rural areas. The implementation of a "One Health" strategy to eliminate malaria in Indonesia by 2030 is strongly recommended.
Background: The focus of this case report is on the role of inflammation as a contributor to pain in plantar fasciitis and its cure by the injection of local anesthetics.
Case presentation: This is a case report on a 24-year-old white man, a middle-distance runner, with chronic unilateral plantar fasciitis and perceived heel pain for almost 1.5 years. He was treated with neural therapy (that is, injection of < 1 ml procaine 1% which is a local anesthetic with strong anti-inflammatory properties) of the surgical scar and along the surgical puncture channel. The follow-up period from the time of first presentation until publication was 2.5 years. At admission, pain intensity (visual analog scale) in the affected leg was severe (10 cm, visual analog scale; range 0–10 cm) when walking and moderate (5 cm, visual analog scale) when standing. After the first session of injections he could stand pain-free and pain when walking was markedly reduced (− 90%). After the third session, he reported no pain in the affected leg and could return to sports at his former level (no difference in training load compared to non-injured state). There was no recurrence of inflammatory signs or heel pain despite intense athletics training up to the date of publication.
Conclusions: In prolonged cases of plantar fasciitis, inflammation is an important component in the development of persistent pain. The results of our case describe the effects of three neural therapy sessions that abolished inflammation and associated heel pain. Neural therapy might be an effective and time-efficient approach in the treatment of plantar fasciitis, enabling an early return to sports.
Objective: Amyloid β (Aβ) depositions in plaques and cerebral amyloid angiopathy (CAA) represent common features of Alzheimer's disease (AD). Sequential deposition of post‐translationally modified Aβ in plaques characterizes distinct biochemical stages of Aβ maturation. However, the molecular composition of vascular Aβ deposits in CAA and its relation to plaques remain enigmatic.
Methods: Vascular and parenchymal deposits were immunohistochemically analyzed for pyroglutaminated and phosphorylated Aβ in the medial temporal and occipital lobe of 24 controls, 27 pathologically‐defined preclinical AD, and 20 symptomatic AD cases.
Results: Sequential deposition of Aβ in CAA resembled Aβ maturation in plaques and enabled the distinction of three biochemical stages of CAA. B‐CAA stage 1 was characterized by deposition of Aβ in the absence of pyroglutaminated AβN3pE and phosphorylated AβpS8. B‐CAA stage 2 showed additional AβN3pE and B‐CAA stage 3 additional AβpS8. Based on the Aβ maturation staging in CAA and plaques, three case groups for Aβ pathology could be distinguished: group 1 with advanced Aβ maturation in CAA; group 2 with equal Aβ maturation in CAA and plaques; group 3 with advanced Aβ maturation in plaques. All symptomatic AD cases presented with end‐stage plaque maturation, whereas CAA could exhibit immature Aβ deposits. Notably, Aβ pathology group 1 was associated with arterial hypertension, and group 2 with the development of dementia.
Interpretation: Balance of Aβ maturation in CAA and plaques defines distinct pathological subgroups of β‐amyloidosis. The association of CAA‐related Aβ maturation with cognitive decline, the individual contribution of CAA and plaque pathology to the development of dementia within the defined Aβ pathology subgroups, and the subgroup‐related association with arterial hypertension should be considered for differential diagnosis and therapeutic intervention.
Neuronal calcium signals propagating by simple diffusion and reaction with mobile and stationary buffers are limited to cellular microdomains. The distance intracellular calcium signals can travel may be significantly increased by means of calcium-induced calcium release from internal calcium stores, notably the endoplasmic reticulum. The organelle, which can be thought of as a cell-within-a-cell, is able to sequester large amounts of cytosolic calcium ions via SERCA pumps and selectively release them into the cytosol through ryanodine receptor channels leading to the formation of calcium waves. In this study, we set out to investigate the basic properties of such dendritic calcium waves and how they depend on the three parameters dendrite radius, ER radius and ryanodine receptor density in the endoplasmic membrane. We demonstrate that there are stable and abortive regimes for calcium waves, depending on the above morphological and physiological parameters. In stable regimes, calcium waves can travel across long dendritic distances, similar to electrical action potentials. We further observe that abortive regimes exist, which could be relevant for spike-timing dependent plasticity, as travel distances and wave velocities vary with changing intracellular architecture. For some of these regimes, analytic functions could be derived that fit the simulation data. In parameter spaces, that are non-trivially influenced by the three-dimensional calcium concentration profile, we were not able to derive such a functional description, demonstrating the mathematical requirement to model and simulate biochemical signaling in three-dimensional space.
Background: Chrysomya megacephala is a blow fly species of medical and forensic importance worldwide. Understanding its bionomics is essential for both designing effective fly control programs and its use in forensic investigations.
Methods: The daily flight activity, seasonal abundance related to abiotic factors (temperature, relative humidity and rainfall) and reproductive potential of this species was investigated. Adult flies were sampled twice a month for one year from July 2013 to June 2014 in three different ecotypes (forest area, longan orchard and palm plantation) of Chiang Mai Province, northern Thailand, using semi-automatic funnel traps. One-day tainted beef offal was used as bait.
Results: A total of 88,273 flies were sampled, of which 82,800 flies (93.8%) were caught during the day (from 06:00 to 18:00 h); while 5473 flies (6.2%) were caught at night (from 18:00 to 06:00 h). Concurrently, the abundance of C. megacephala was higher in the forest area (n = 31,873; 36.1%) and palm plantation (n = 31,347; 35.5%), compared to the longan orchard (n = 25,053; 28.4%). The number of females was significantly higher than that of males, exhibiting a female to male sex ratio of 2.36:1. Seasonal fluctuation revealed the highest abundance of C. megacephala in summer, but low numbers in the rainy season and winter. Fly density was significantly positively correlated with temperature, but negatively correlated with relative humidity. No correlation between numbers of C. megacephala with rainfall was found. Activity occurred throughout the daytime with high numbers from 06:00 to 18:00 h in summer and 12:00 to 18:00 h in the rainy season and winter. As for the nocturnal flight activity, a small number of flies were collected in summer and the rainy season, while none were collected in the winter. Dissection of the females indicated that fecundity was highest during the rainy season, followed by winter and summer.
Conclusions: Since the assessment of daily, seasonal activity and the reproductive potential of C. megacephala remains a crucial point to be elucidated, this extensive study offers insights into bionomics, which may be considered for integrated fly control strategies and forensic entomology issues.
Background: Sputum induction is an important noninvasive method for analyzing bronchial inflammation in patients with asthma and other respiratory diseases. Most frequently, ultrasonic nebulizers are used for sputum induction, but breath-controlled nebulizers may target the small airways more efficiently. This treatment may produce a cell distribution similar to bronchoalveolar lavage (less neutrophils and more macrophages) and provide deeper insights into the underlying lung pathology. The goal of the study was to compare both types of nebulizer devices and their efficacy in inducing sputum to measure bronchial inflammation, i.e., cell composition and cytokines, in patients with mild allergic asthma and healthy controls.
Methods: The population of this study consisted of 20 healthy control subjects with a median age of 17 years, range: 8–25 years, and 20 patients with a median age of 12 years, range: 8–24 years, presenting with mild, controlled allergic asthma who were not administered an inhaled steroid treatment. We induced sputum in every individual using both devices on two separate days. The sputum weight, the cell composition and cytokine levels were analyzed using a cytometric bead assay (CBA) and by real-time quantitative PCR (qRT-PCR).
Results: We did not observe significant differences in the weight, cell distribution or cytokine levels in the sputum samples induced by both devices. In addition, the Bland-Altman correlation revealed good concordance of the cell distribution. As expected, eosinophils and IL-5 levels were significantly elevated in patients with asthma.
Conclusions: The hypothesis that sputum induction with a breath-controlled "smart" nebulizer is more efficient and different from an ultrasonic nebulizer was not confirmed. The Bland-Altman correlations showed good concordance when comparing the two devices.
Trial registration: NCT01543516 Retrospective registration date: March 5, 2012.
Background: In intensive care units (ICU) octogenarians become a routine patients group with aggravated therapeutic and diagnostic decision-making. Due to increased mortality and a reduced quality of life in this high-risk population, medical decision-making a fortiori requires an optimum of risk stratification. Recently, the VIP-1 trial prospectively observed that the clinical frailty scale (CFS) performed well in ICU patients in overall-survival and short-term outcome prediction. However, it is known that healthcare systems differ in the 21 countries contributing to the VIP-1 trial. Hence, our main focus was to investigate whether the CFS is usable for risk stratification in octogenarians admitted to diversified and high tech German ICUs.
Methods: This multicentre prospective cohort study analyses very old patients admitted to 20 German ICUs as a sub-analysis of the VIP-1 trial. Three hundred and eight patients of 80 years of age or older admitted consecutively to participating ICUs. CFS, cause of admission, APACHE II, SAPS II and SOFA scores, use of ICU resources and ICU- and 30-day mortality were recorded. Multivariate logistic regression analysis was used to identify factors associated with 30-day mortality.
Results: Patients had a median age of 84 [IQR 82–87] years and a mean CFS of 4.75 (± 1.6 standard-deviation) points. More than half of the patients (53.6%) were classified as frail (CFS ≥ 5). ICU-mortality was 17.3% and 30-day mortality was 31.2%. The cause of admission (planned vs. unplanned), (OR 5.74) and the CFS (OR 1.44 per point increase) were independent predictors of 30-day survival.
Conclusions: The CFS is an easy determinable valuable tool for prediction of 30-day ICU survival in octogenarians, thus, it may facilitate decision-making for intensive care givers in Germany.
Trial registration: The VIP-1 study was retrospectively registered on ClinicalTrials.gov (ID: NCT03134807) on May 1, 2017.
This study explores anomalies in stock returns found in their seasonal patterns. These are verified through multiple trading strategies based on past-performance returns that require information up to 20 years in the past. Some of the presented strategies deliver relatively high performance, especially for those strategies based on returns in the same calendar month from past years. In order to minimize any possible bias due to omitted delisting returns, those are incorporated into the monthly returns. Furthermore, to find an explanation for this seasonal effect, behavioral theories are discussed and the returns are controlled for risk and mispricing factors. However, empirical evidence indicates no evidence of explanation based on these factors for the seasonal patterns. Furthermore, possible reasons why the returns persist are discussed.
A growing body of literature shows the importance of financial literacy in households' financial decisions. However, fewer studies focus on understanding the determinants of financial literacy. Our paper fills this gap by analyzing a specific determinant, the educational system, to explain the heterogeneity in financial literacy scores across Germany. We suggest that the lower financial literacy observed in East Germany is partially caused by a different institutional framework experienced during the Cold War, more specifically, by the socialist educational system of the GDR which affected specific cohorts of individuals. By exploiting the unique set-up of the German reunification, we identify education as a channel through which institutions and financial literacy are related in the German context.
Authoritarian regimes and religious institutions in the Muslim majority world see eye-to-eye on the topic of atheism. United by their fear of losing control over their populations and their desire for conformity, consecutive governments have pushed for unfair restrictions on their subjects’ beliefs since their inception. But even in society, non-belief remains a taboo. Should atheists in Muslim majority world become more vocal?
With the rise of big data, internet-of-things, machine learning, targeted advertising, face recognition algorithms, virtual assistants, cyberbullying, cyberstalking, and cyberwarfare, we find more and more people and policy makers around the world debating whether technological advances are helping us or hurting us. Such debates often focus on trying to figure out a way to balance the need to preserve human values with the desire to not interfere with technological progress. The central problem that arises then is what to do when values and progress come into direct conflict with each other. Should we err on the side of caution and rein in companies like Google, Twitter, and Facebook so they do not interfere with personal privacy and national democracy? Or should we take a more pioneering perspective and view the occasional rights violation as a necessary risk that can be outweighed by the rewards for medicine, manufacturing, and media? Or should we try to find a middle path and have tech companies and policy makers work together to develop guidelines for “responsible research and innovation”?
Large-scale digitisation has brought cultural heritage objects and materials from the remotest places of the world to our computer screens. At first sight, this innovation seems to make cultural heritage accessible to everyone like never before. However, technological advances have not eliminated social inequalities between powerful and marginalized communities and ethical issues in communicating cultural heritage. These issues became much more vivid and obvious when the spread of cultural heritage reached the global scale.
Bridge International is a for-profit chain of private (pre-)primary schools employing technology to allegedly provide “high-quality, affordable education” in the Global South. Like many other actors, Bridge (cl)aims to bridge the global digital divide and to use information and communication technologies to realize development (“ICT4D”), in particular in sub-Saharan Africa. But are such projects really allowing the region to “catch up” with the rest of the world and strengthen its weak global standing? Not necessarily. Many projects’ implementation mirrors existing global power inequalities and may even reinforce them.1 Moreover, the technologies employed themselves augment these imbalances. The present contribution illustrates this, using Bridge as a case study.
Das Internet ist ein gigantisches Netzwerk von Maschinen. Während sich dessen konkrete Nutzung permanent weiterentwickelt, bleibt dessen Funktion im Kern doch immer der Austausch von Informationen. Die vielfältigen Institutionen der Internet Governance lassen sich als Versuch verstehen, diesen Austausch zu ermöglichen. Eine zentrale Rolle kommt dabei der Internet Corporation for Assigned Names and Numbers (ICANN) zu. Sie verwaltet das globale Adressbuch des Internets und legt so fest, wie weit das Netz des Internets reicht. Die technische Notwendigkeit einer solchen zentralen Instanz wird im Prinzip kaum bestritten. Zunehmend jedoch verschärfen sich die Konflikte darüber, wie weit deren Kompetenzen reichen und wer sie kontrollieren sollte. Letztlich, so möchte ich zeigen, geht es um die Frage, wieviel internationale Autorität in diesem Bereich der Internet Governance notwendig und legitim ist.
Europe’s new digital borders
(2018)
The European Union’s (EU) external border framework is not only increasingly reliant on digital databases, but these databases are now set to become interoperable. By 2020, the European Commission (EC) aims to have a fully interconnected new architecture for identity management at the border in place. Based on biometric enrolment of all third-country citizens, Europe’s new digital borders raise a number of concerns, including suspicion, large-scale surveillance, and internal policing that spread well beyond the border site.
Border management today is embedded into a complex network of data collection and data analysis that provides authorities with knowledge about who (or what) attempts to cross the border. While still serving as physical chokepoints for the examination and extraction of dangerous, suspicious, or illegitimate elements from global flows of mobility, border operations therefore increasingly rely on a number of databases...
The discussion about the interplay between digital technologies and the process of globalization is often focused around the following question: who has access to global information networks and who benefits from digital communication technologies? These are essential questions and it can hardly be denied that they confront us with a series of political and ethical questions. However, we also need to recognize the ongoing digitalization of the globe, a process where more and more people are put on various kinds of maps...
Almost a decade ago, the internet was celebrated as one of history’s greatest liberation tools. People have unparalleled access to information and a greater deal of freedom to express themselves without fear of censorship or reprisal. This enthusiasm was short-lived, however. Today’s internet is heaving with hate speech, censorship, fake news, misinformation, and all forms of extremism. Governments have tightened their grip on digital spaces, and tech companies have grown into nontransparent empires with immense influence on the world’s politics, economies, and societies. These changes have brought forward new terrains of conflict and have redefined the relationship between the citizen and the state.
Hypofunction of the N-methyl-D-aspartate receptor (NMDAR) has been implicated as a possible mechanism underlying cognitive deficits and aberrant neuronal dynamics in schizophrenia. To test this hypothesis, we first administered a sub-anaesthetic dose of S-ketamine (0.006 mg/kg/min) or saline in a single-blind crossover design in 14 participants while magnetoencephalographic data were recorded during a visual task. In addition, magnetoencephalographic data were obtained in a sample of unmedicated first-episode psychosis patients (n = 10) and in patients with chronic schizophrenia (n = 16) to allow for comparisons of neuronal dynamics in clinical populations versus NMDAR hypofunctioning. Magnetoencephalographic data were analysed at source-level in the 1–90 Hz frequency range in occipital and thalamic regions of interest. In addition, directed functional connectivity analysis was performed using Granger causality and feedback and feedforward activity was investigated using a directed asymmetry index. Psychopathology was assessed with the Positive and Negative Syndrome Scale. Acute ketamine administration in healthy volunteers led to similar effects on cognition and psychopathology as observed in first-episode and chronic schizophrenia patients. However, the effects of ketamine on high-frequency oscillations and their connectivity profile were not consistent with these observations. Ketamine increased amplitude and frequency of gamma-power (63–80 Hz) in occipital regions and upregulated low frequency (5–28 Hz) activity. Moreover, ketamine disrupted feedforward and feedback signalling at high and low frequencies leading to hypo- and hyper-connectivity in thalamo-cortical networks. In contrast, first-episode and chronic schizophrenia patients showed a different pattern of magnetoencephalographic activity, characterized by decreased task-induced high-gamma band oscillations and predominantly increased feedforward/feedback-mediated Granger causality connectivity. Accordingly, the current data have implications for theories of cognitive dysfunctions and circuit impairments in the disorder, suggesting that acute NMDAR hypofunction does not recreate alterations in neural oscillations during visual processing observed in schizophrenia.
The large number of species still to be discovered in fungi, together with an exponentially growing number of environmental sequences that cannot be linked to known taxa, has fuelled the idea that it might be necessary to formally name fungi on the basis of sequence data only. Here we object to this idea due to several shortcomings of the approach, ranging from concerns regarding reproducibility and the violation of general scientific principles to ethical issues. We come to the conclusion that sequence-based nomenclature is potentially harmful for mycology as a discipline. Additionally, a classification based on sequences as types is not within reach anytime soon, because there is a lack of consensus regarding common standards due to the fast pace at which sequencing technologies develop.
With the change to one scientific name for pleomorphic fungi, generic names typified by sexual and asexual morphs have been evaluated to recommend which name to use when two names represent the same genus and thus compete for use. In this paper, generic names in Pucciniomycotina and Ustilaginomycotina are evaluated based on their type species to determine which names are synonyms. Twenty-one sets of sexually and asexually typified names in Pucciniomycotina and eight sets in Ustilaginomycotina were determined to be congeneric and compete for use. Recommendations are made as to which generic name to use. In most cases the principle of priority is followed. However, eight generic names in the Pucciniomycotina, and none in Ustilaginomycotina, are recommended for protection: Classicula over Naiadella, Gymnosporangium over Roestelia, Helicobasidium over Thanatophytum and Tuberculina, Melampsorella over Peridermium, Milesina over Milesia, Phragmidium over Aregma, Sporobolomyces over Blastoderma and Rhodomyces, and Uromyces over Uredo. In addition, eight new combinations are made: Blastospora juruensis, B. subneurophyla, Cronartium bethelii, C. kurilense, C. sahoanum, C. yamabense, Milesina polypodii, and Prospodium crusculum combs. nov.
Soluble Triggering Receptor Expressed on Myeloid Cells 1 (sTREM-1) can be found in the sera of patients with infectious, autoimmune and malignant diseases. The primary objective of this study was to investigate the prognostic significance of sTREM-1 in lung cancer patients. We analyzed the sera of 164 patients with lung cancer of all histologies and all stages at the time of diagnosis. We employed an ELISA using the anti-TREM-1 clone 6B1.1G12 mAb and recombinant human TREM-1. Patient data was collected retrospectively by chart review. In ROC-analysis, a sTREM-1 serum level of 163.1 pg/ml showed the highest Youden-Index. At this cut-off value sTREM-1 was a marker of short survival in patients with NSCLC (median survival 8.5 vs. 13.3 months, p = 0.04). A Cox regression model showed stage (p < 0.001) and sTREM-1 (p = 0.011) to indicate short survival. There were no differences in sTREM-1 serum values among patients with or without infection, pleural effusion or COPD. sTREM-1 was not associated with metastasis at the time of diagnosis and was not a predictor of subsequent metastasis. In SCLC patients sTREM-1 levels were lower than in NSCLC patients (p = 0.001) and did not predict survival. sTREM-1 did not correlate with CRP or the number of neutrophils. In non-small cell lung cancer patients, sTREM-1 in serum has prognostic significance.
Growing evidence suggests that distributed spatial attention may invoke theta (3–9 Hz) rhythmic sampling processes. The neuronal basis of such attentional sampling is, however, not fully understood. Here we show using array recordings in visual cortical area V4 of two awake macaques that presenting separate visual stimuli to the excitatory center and suppressive surround of neuronal receptive fields (RFs) elicits rhythmic multi-unit activity (MUA) at 3–6 Hz. This neuronal rhythm did not depend on small fixational eye movements. In the context of a distributed spatial attention task, during which the monkeys detected a spatially and temporally uncertain target, reaction times (RTs) exhibited similar rhythmic fluctuations. RTs were fast or slow depending on the target occurrence during high or low MUA, resulting in rhythmic MUA-RT cross-correlations at theta frequencies. These findings show that theta rhythmic neuronal activity can arise from competitive RF interactions and that this rhythm may result in rhythmic RTs potentially subserving attentional sampling.
Dinge, die warten
(2018)
Das Wort 'warten' gehört zu den Verben, die wir ohne Probleme allem anhängen können. Die Menschen können nicht nur den Menschen, sondern auch den Dingen jederzeit ein Warten unterschieben und allem, was dazwischen ist, sowieso. Die Raubtiere warten darauf, gefüttert zu werden; die berühmte Zecke wartet, bis etwas vorbeikommt; die Pflanzen warten auf den Regen. Vor dem Gewitter scheint die Natur auf etwas zu warten. All das sagt sich so: Diese Worte warten darauf, ausgesprochen zu werden. Hier geht es nicht bloß um die Banalität, dass wir den Dingen mit unseren Worten unablässig Tätigkeiten anhängen, die ihnen im wörtlichen Sinne nicht zukommen. Der Versuch, eine Grenze zu ziehen zwischen einer eigentlichen und einer uneigentlichen - also metaphorischen - Verwendung des Wortes warten, würde das Problem lediglich zudecken.
Es ist oft gesagt worden: Das Komische ist das Eigene des Menschen, nur der Mensch - und kein anderes Wesen - lacht. Begründet wurde dies häufig durch die Kennzeichnung des Menschen als Doppelwesen, das sich selbst widersprechen kann. Der Mensch gilt als Wesen, das gleichermaßen über einen Körper und einen Geist verfügt, als Wesen, das vom Zufall heimgesucht wird, aber auch zum Erhabenen fähig ist, oder als Wesen, das durch eine "individuelle[ ]" und eine "soziale[ ] Existenz" ausgezeichnet ist und deshalb "mit irgendeiner Norm" in Konflikt geraten kann. Jeweils ist es die Kollision der beiden Seiten, die nach den verschiedenen theoretischen Ansätzen zur Hervorbringung des komischen Phänomens führt und so - als Reaktion auf die Wahrnehmung des komischen Phänomens - das Lachen verursacht.
Stumme Diener, menschliche wie nichtmenschliche, sind entgegen ihrer Bezeichnung "things that talk", Stumme Diener können gar nicht anders, als doch zu reden. Ihre abgewandten, verstellten Stimmen, ihr Flüstern und Murmeln bei halbgeöffnetem Mund gilt es zu vernehmen. Nicht nur der Subalterne spricht, auch die Dinge. Sie können gar nicht anders als im Modus des Stummgeschaltet-Seins dennoch mitzureden mit Hilfe der um sie herumgelagerten Geschichten. Stumme Diener sind Medien, die Sprechen machen.
Die Akteur-Netzwerk-Theorie (ANT) zählt nicht nur humane Akteure - im Fall der Literatur: Figuren - zu Handlungsträgern. Auch Dinge handeln, weshalb Bruno Latour sie mit dem Semiotiker Algirdas Greimas als 'Aktanten' bezeichnet. Die ANT versucht, das Zusammenwirken humaner wie nichthumaner Aktanten zu beschreiben. Akteur-Netzwerk-Soziolog_innen erstellen hierfür einen Bericht von dem, was Latour in Eine neue Soziologie für eine neue Gesellschaft. Einführung in die Akteur-Netzwerk-Theorie das 'Soziale Nr. 2' oder das 'Soziale der Assoziationen' nennt, die Verbindungen und Zwischenwirkungen der Aktanten, die in der Soziologie unbeachtet geblieben seien. Die Soziolog_innen sollen dabei den Dingen 'kurzsichtig' folgen und deren Handlungsvermögen (agency) weniger "steif" und "hölzern" darstellen, sondern sich in ihren Berichten die Literatur zum Vorbild nehmen.
"Wir wissen nichts vom Sozialen, was nicht durch unser Wissen vom Natürlichen definiert wäre und umgekehrt." Was Bruno Latour für die Soziologie der modernen Wissenschaften formuliert, gilt, seit ihren Anfängen, für die von Übertragungen und Analogieschlüssen bestimmte Begriffsgeschichte der Naturlehre überhaupt: Die 'Ordnung der Dinge' in der Natur und gemäß ihrer jeweiligen Natur entspringt dem Ordnungsdenken sozialer Wesen, die ihre eigenen Belange in Orientierung an Konzeptionen der Natur zu regeln versuchen. Ein solches Denken der menschlichen in Analogie oder Kontrast zu den nichtmenschlichen Dingen setzt die kategoriale Geschiedenheit zweier Sphären voraus, deren Ordnungsmuster einander nun wechselseitig konturieren und stabilisieren.
Menschliches Leben vollzieht sich notwendigerweise mit Hilfe des Gebrauchs von Dingen. Versteht man unter Dingen - in bewusster Umgehung aller definitorischen und philosophischen Abgrenzungsprobleme - alle natürlichen und artifiziellen Entitäten, die unbelebt, sprachlos und mobil sind, dann kann man insgesamt vier Bereiche von Dingen identifizieren, die für menschliche Handlungen zentral sind: 1. der Bereich des Körpers (hierher gehören die Unterbereiche von Wohnen, Kleiden, Essen und Sport mit Dingen wie Möbeln, Essgeschirr und etwa Schlägern und Bällen), 2. Kommunikation und Verkehr (hierher gehören neben Autos, Telefonen und Büchern auch Spiele, Musikinstrumente, Bilder und Kunst), 3. Krieg (Waffen) und 4. schließlich die Arbeit (mit der ganzen Fülle von Instrumenten und Werkzeugen). Selbstverständlich gibt es Mischformen, Steine etwa können zum Wohnen gehören, wenn aus ihnen die Wände der Häuser gebaut werden, zum Krieg, wenn eine Steinschleuder zum Einsatz kommt, oder zur Arbeit, wenn Mauern oder Pyramiden gebaut werden oder einfach alle Werkzeuge aus Stein sind, wie in der Steinzeit.
Der Artikel diskutiert die Arbeit von Paläopathologen, die diverse Krankheiten von Menschen der Vormoderne mittels mikroskopischer Untersuchungen an ihren Skeletten nachweisen können. Anhand der Befunde eines 4300 Jahre alten Skelettes erzählt die SZ-Autorin eine überraschend detaillierte, wenn auch knappe Lebensgeschichte eines Menschen - sie bettet die wissenschaftlichen Ergebnisse in ein Narrativ ein.
Was versteht man gemeinhin unter Indizien? Indizien (indicium: An-Zeichen) beweisen ja vermeintlich keine Tat oder Schuld, sondern verweisen nur auf diese - eine spekulative, geradezu dubiose Uneindeutigkeit wird mit dem Indiz assoziiert. Dieses noch heute verbreitete Indizienverständnis resultiert historisch aus einer strafrechtlichen Debatte, die im 18. Jahrhundert den Status von Indizien äußerst konträr diskutiert, wobei deren - vermeintliche - Objektivität (Tatsache, Faktum) gegen einen - fehleranfälligen - Interpretationsspielraum (Zeichen, Denkschluss) in Anschlag gebracht wird.
Lexika wie Zedlers Universal-Lexicon gehen von einer scharfen Trennung zwischen Objekt und Subjekt aus, Schreibwerkzeuge werden darin immer auf die Objektseite geschlagen. Sprechende und damit subjektivierte Federn gibt es hingegen schon, seit Federn in Gebrauch sind. Sie tun dies vor allem in literarischen Texten, wo sie als dingliche Objekte Subjektstatus einnehmen und dadurch die Dichotomie von Subjekt und Objekt unterlaufen. Wenn die Feder zum sprechenden Subjekt wird, werden die von ihr beschriebenen Menschen zum Objekt, wobei sich die Feder dann für Benachteiligte und Unterdrückte einsetzt und dadurch diese wiederum zu Subjekten erhebt. Innerhalb der It-Narratives nehmen erzählende Federn eine Sonderstellung ein, weil sie erstens die materielle Vorbedingung des Schreibens sind, weil sie zweitens den Schwellenraum von Mündlichkeit und Schriftlichkeit besetzen, indem sie paradoxerweise das, was sie sprechen, auch gleichzeitig ins Schriftliche transponieren und dort festschreiben, sowie weil sie drittens poetologisch das hinterfragen, was geschrieben wird und werden soll
Die Hölle ist - nimmt man Hieronymus Boschs Triptychon Der Garten der Lüste (um 1500) und darin insbesondere die 'Musikalische Hölle' in den Blick - vor allem ein Ort der unheilvollen Dinge. Diese stehen in Boschs Darstellung allerdings nicht lediglich symbolisch für Laster und Sündhaftigkeit, sondern setzen zugleich die Strafen für diese Sünden ebenso verstörend wie ästhetisch in Szene. Was den Menschen in diese Hölle bringt, beschreibt die 1587 erschienene Historia von D. Johann Fausten. Es ist, wie im Folgenden gezeigt werden soll, das Begehren, über die Dinge und das Materielle zu herrschen. Dabei wird sich erweisen, wie der Teufel nicht nur die Konzentration auf die Oberfläche der Dinge befördert, sondern auch, wie er die Verunsicherung der Relation von verba und res sowie die Veruneindeutigung der Relation der res zur Realität einsetzt, um der Seele des Protagonisten habhaft zu werden. Dem sogenannten Schwankteil sowie dem Schluss der Historia soll hierbei besondere Aufmerksamkeit zukommen.
Objektiviertes Begehren : zur Funktion und Bedeutung von Gegenständen in mittelhochdeutschen Mären
(2018)
Die in Mären dargestellten Handlungen konzentrieren sich auf einen spezifischen, außerordentlichen und in sich geschlossenen Fall, der sowohl Vorfall wie auch Zufall oder Rechtsfall sein kann. Didaktisches Substrat, schwankhaftes Erzählen und Exempelliteratur verschmelzen in dieser paargereimten Erzählform.
Dinge, denen besondere Eigenschaften oder Wirkungsweisen zugeschrieben werden, tauchen in der mittelalterlichen Literatur allenthalben auf. Sei es, dass sie einem anderweltlichen Bereich entstammen wie Siegfrieds Tarnkappe im Nibelungenlied oder der Paradiesstein im Alexanderroman, sei es, dass eigentlich 'gewöhnliche' Dinge in den Fokus der Erzählung rücken wie der Schmuck der Jeschute in Wolframs Parzival oder Brünhilds Gürtel - in bestimmten Konstellationen werden Dinge zu 'Mitspielern', deren handlungsdeterminierende Macht derjenigen der menschlichen Protagonisten um nichts nachsteht. Dass Dinge 'handeln', ist in den Texten des Mittelalters keine Seltenheit.
Was macht eine höfisch kultivierte Dame oder einen höfischen Ritter aus? Die mittelalterliche, von Frankreich ausgehende Artusepik antwortet auf diese Frage unter Bezug auf drei Komponenten, nämlich eine edle Abkunft (Geburtsadel), eine edle Gesinnung (Tugendadel) und einen gewissen höfischen Lebensstil, zu dem, ganz zentral, auch höfische Luxus- und Repräsentationsobjekte gehören, so etwa ritterliche Bewaffnung und kostbare Kleidung. Was passiert, wenn es an einer Harmonie von innen und außen öffentlich sichtbar mangelt und die Wirkungseinheit von Mensch und Repräsentationsobjekt zu Bruch geht, zeigt uns die mittelalterliche Erzählung vom schlecht geschnittenen Mantel, altfranzösisch: du mantel mautaillé. Sie nimmt in Frankreich des 13. Jahrhunderts (zwischen 1200 und 1210) ihren Anfang, und zwar in Gestalt des Lais (Le lay du cort mantel), einer kurzen Verserzählung keltischer Stoffe (lai narratif ), und verbreitet sich rasch in Europa.
Vor rund 25 Jahren bemerkte David Wells in einem Aufsatz, in dem er die mittelalterliche Literatur hinsichtlich allegorischer Verfahren untersuchte, der Löwe in Hartmanns von Aue Iwein brülle geradezu nach seiner Interpretation. Ausführlich verzeichnet er die zuvor versuchten Deutungen, die sich bis zum Erscheinen des Aufsatzes im Jahre 1992 auf knapp 20 belaufen. Seine kleine Anmerkung illustriert die große Unsicherheit im interpretativen Umgang mit Dingen in der mittelalterlichen Literatur, aber ebenso ihr großes interpretatorisches Potential.
Die Beziehung von res und verba ist ihrem Grunde nach eine sprachphilosophische. Sie handelt von jenen Dingen, die überhaupt der Sprache zugänglich sind, bzw. von jenen Gegenständen, welche durch ihre Artikulation erst zu Dingen der Sprache werden. Der Fokus der Überlegungen konzentriert sich auf die Organisation des Verhältnisses von res und verba, für das über Jahrtausende hinweg in erster Linie die Rhetorik zuständig gewesen ist. Diesem liegen allerdings tatsächlich zwei sprachphilosophische Annahmen zugrunde, die von gegensätzlichen Voraussetzungen ausgehen.
Dinge in Texten haben maßgeblich an der Konstruktion imaginärer Welten teil. Sie kommen zu allen Zeiten und in allen literarischen Gattungen vor, in der Heldenepik ebenso wie in Aphorismen, im Mittelalter wie in der Moderne. Dinge treiben Handlungen voran, stören, wenn sie nicht funktionieren, und sie schaffen und zerstören Ordnungen - auch solche der Worte. Im Gegensatz zur Ethnologie oder Museologie hat es die Literaturwissenschaft stets mit Zeichen zu tun - es stellt sich also die Frage, wie das Verhältnis von res und verba analysiert und beschrieben werden kann. Der vorliegende Band versammelt Beiträge, die sich, angefangen bei der antiken Rhetorik über mittelalterliche Literatur bis hin zum 20. Jahrhundert, mit Dingen in und neben Texten beschäftigen.
Diese Arbeit trägt dazu bei, die Lutherdarstellung in Lehr- und Schulbüchern der ersten Schulbuchgeneration systematisch zu erschließen. Sie stellt sich der Herausforderung den jeweils spezifischen Akzent der Lutherdarstellung und -konzeption, welcher in den Lehrtexten des Lehrbuchs transportiert wird, herauszuarbeiten und weitergehend im Verbund mit den anderen untersuchten Lehrbüchern auf übergreifende, verbindende und trennende Elemente zu untersuchen. Diese Forschungsarbeit leistet einen Beitrag zur Erschließung Luthers sowie ihrer Art und Intensität in dem Medium des Schulbuchs im Kontext der Aufklärung. Insgesamt werden zehn Werke von acht Autoren im Zeitraum von 1780 bis 1817 untersucht, darunter Schulbücher von Johann Matthias Schröckh, Lorenz von Westenrieder und Jakob Brand.
Social identification has been shown to be a protective resource for mental health. In this study, the relationships between social identification and emotional, as well as cognitive symptoms of test anxiety are investigated. Participants were university students diagnosed with test anxiety (N = 108). They completed questionnaires regarding a range of psychopathologic stress symptoms, and their social identification with fellow students and with their study program. Results reveal negative relations between social identification and almost all investigated emotional and cognitive symptoms of test anxiety. Based on this study, interventions could be developed that strengthen the social identity of university students.
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.
Introduction: This study was designed to evaluate risk factors and incidence of epilepsy-related injuries and accidents (ERIA) at an outpatient clinic of a German epilepsy center providing healthcare to a mixed urban and rural population of over one million inhabitants.
Methods: Data acquisition was performed between 10/2013 and 09/2014 using a validated patient questionnaire on socioeconomic status, course of epilepsy, quality of life (QoL), depression, injuries and accidents associated with seizures or inadequate periictal patterns of behavior concerning a period of 3 months. Univariate analysis, multiple testing and regression analysis were performed to identify possible variables associated with ERIA.
Results: A total of 292 patients (mean age 40.8 years, range 18–86; 55% female) were enrolled and analyzed. Focal epilepsy was diagnosed in 75% of the patients. The majority was on an antiepileptic drug (AEDs) polytherapy (mean number of AEDs: 1.65). Overall, 41 patients (14.0%) suffered from epilepsy-related injuries and accidents in a 3-month period. Besides lacerations (n = 18, 6.2%), abrasions and bruises (n = 9, 3.1%), fractures (n = 6, 2.2%) and burns (n = 3, 1.0%), 17 mild injuries (5.8%) were reported. In 20 (6.8% of the total cohort) cases, urgent medical treatment with hospitalization was necessary. Epilepsy-related injuries and accidents were related to active epilepsy, occurrence of generalized tonic-clonic seizures (GTCS) and drug-refractory course as well as reported ictal falls, ictal loss of consciousness and abnormal peri-ictal behavior in the medical history. In addition, patients with ERIA had significantly higher depression rates and lower QoL.
Conclusion: ERIA and their consequences should be given more attention and standardized assessment for ERIA should be performed in every outpatient visit.
Synaptic vesicle (SV) recycling enables ongoing transmitter release, even during prolonged activity. SV membrane and proteins are retrieved by ultrafast endocytosis and new SVs are formed from synaptic endosomes (large vesicles—LVs). Many proteins contribute to SV recycling, e.g., endophilin, synaptojanin, dynamin and clathrin, while the site of action of these proteins (at the plasma membrane (PM) vs. at the endosomal membrane) is only partially understood. Here, we investigated the roles of endophilin A (UNC-57), endophilin-related protein (ERP-1, homologous to human endophilin B1) and of clathrin, in SV recycling at the cholinergic neuromuscular junction (NMJ) of C. elegans. erp-1 mutants exhibited reduced transmission and a progressive reduction in optogenetically evoked muscle contraction, indicative of impaired SV recycling. This was confirmed by electrophysiology, where particularly endophilin A (UNC-57), but also endophilin B (ERP-1) mutants exhibited reduced transmission. By optogenetic and electrophysiological analysis, phenotypes in the unc-57; erp-1 double mutant are largely dominated by the unc-57 mutation, arguing for partially redundant functions of endophilins A and B, but also hinting at a back-up mechanism for neuronal endocytosis. By electron microscopy (EM), we observed that unc-57 and erp-1; unc-57 double mutants showed increased numbers of synaptic endosomes of large size, assigning a role for both proteins at the endosome, because endosomal disintegration into new SVs, but not formation of endosomes were hampered. Accordingly, only low amounts of SVs were present. Also erp-1 mutants show reduced SV numbers (but no increase in LVs), thus ERP-1 contributes to SV formation. We analyzed temperature-sensitive mutants of clathrin heavy chain (chc-1), as well as erp-1; chc-1 and unc-57; chc-1 double mutants. SV recycling phenotypes were obvious from optogenetic stimulation experiments. By EM, chc-1 mutants showed formation of numerous and large endosomes, arguing that clathrin, as shown for mammalian synapses, acts at the endosome in formation of new SVs. Without endophilins, clathrin formed endosomes at the PM, while endophilins A and B compensated for the loss of clathrin at the PM, under conditions of high SV turnover.
Background: Severely injured patients experience substantial immunological stress in the aftermath of traumatic insult, which often results in systemic immune dysregulation. Regulatory T cells (Treg) play a key role in the suppression of the immune response and in the maintenance of immunological homeostasis. Little is known about their presence and dynamics in blood after trauma, and nothing is known about Treg in the porcine polytrauma model. Here, we assessed different subsets of Treg in trauma patients (TP) and compared those to either healthy volunteers (HV) or data from porcine polytrauma.
Methods: Peripheral blood was withdrawn from 20 TP with injury severity score (ISS) ≥16 at the admittance to the emergency department (ED), and subsequently on day 1 and at day 3. Ten HV were included as controls (ctrl). The porcine polytrauma model consisted of a femur fracture, liver laceration, lung contusion, and hemorrhagic shock resulting in an ISS of 27. After polytrauma, the animals underwent resuscitation and surgical fracture fixation. Blood samples were withdrawn before and immediately after trauma, 24 and 72 h later. Different subsets of Treg, CD4+CD25+, CD4+CD25+FoxP3+, CD4+CD25+CD127−, and CD4+CD25+CD127−FoxP3+ were characterized by flow cytometry.
Results: Absolute cell counts of leukocytes were significantly increasing after trauma, and again decreasing in the follow-up in human and porcine samples. The proportion of human Treg in the peripheral blood of TP admitted to the ED was lower when compared to HV. Their numbers did not recover until 72 h after trauma. Comparable data were found for all subsets. The situation in the porcine trauma model was comparable with the clinical data. In porcine peripheral blood before trauma, we could identify Treg with the typical immunophenotype (CD4+CD25+CD127−), which were virtually absent immediately after trauma. Similar to the human situation, most of these cells expressed FoxP3, as assessed by intracellular FACS stain.
Conclusion: Despite minor percental differences in the recovery of Treg populations after trauma, our findings show a comparable decrease of Treg early after polytrauma, and strengthen the immunological significance of the porcine polytrauma model. Furthermore, the Treg subpopulation CD4+CD25+CD127− was characterized in porcine samples.
Nach Jakobson (1941) lassen sich in der frühen phonologischen Entwicklung zwei diskrete Phasen unterscheiden. Eine erste Phase, in der vorsprachliche Lalllaute produziert werden und keine phonologischen Kontraste gegeben sind, und eine zweite Phase, die eigentliche Sprachstufe, in der eben diese sprachsystematischen Kontrastbildungen sukzessive ausgebaut werden. Ausgehend von diesem strukturalistischen Paradigma wurden Protowörter, die im Übergang von der Lallphase zur Zielwortproduktion realisiert werden und bei einer relativ stabilen Bedeutungszuweisung keine overte Ähnlichkeit zu Zielwörtern zeigen, entweder als artikulatorische Muster analysiert oder unter der Perspektive der Generativen Grammatik als nicht-phonologische Wortformen gänzlich ignoriert. Im Gegensatz zu diesen tradierten Ansätzen wird in dieser Arbeit ein neuer Ansatz vertreten, nach dem dreidimensionale (mit segmentaler, silbischer und metrischer Ebene) phonologische Repräsentationen ab ovo in der Sprachverarbeitung aktiv sind und sich gemäß der klassischen Kompetenz-Performanz-Unterscheidung in frühen Wortproduktionen auch linguistisch analysieren lassen. Das adäquate Instrumentarium für diese Analyse können gerade nicht zielsprachliche Merkmalskontraste mit bedeutungsunterscheidender Funktion sein, sondern genuin phonologische Kontraste. Zielführend ist hier die Anwendung der Demisilbentheorie von Clements (1990), mit deren Hilfe die phonologische Komplexität von Demisilben nach Maßgabe von Sonorität berechnet werden. Wurde diese Theorie bisher erfolgreich in der Aphasiologie angewendet, wird sie hier erstmals in der Untersuchung der Protowortproduktion, appliziert. Die Daten stammen aus der im Rahmen dieser Arbeit durchgeführten Einzelfallstudie, in der die Spontansprachproduktionen von Kind J., 1;4 Jahre, jeweils einmal wöchentlich für 30 Minuten aufgezeichnet wurden. Die Aufnahmen endeten zu dem Zeitpunkt, als Kind J. keine Protowörter mehr produzierte. Wesentliche Ergebnisse einer linguistisch-qualitativen wie auch einer statistisch-quantitativen Analyse dieser Daten waren, dass Proto- und Zielwortproduktion korrelierten, d.h., bei Abnahme der Protowortproduktion die Zielwortproduktion zunahm; beide Wortklassen tendenziell aus nicht-komplexen Demisilben aufgebaut waren und Protowörter in dem Sinne als Vorläufer von Zielwörtern angesehen werden können, als dass bei ihnen nicht die zielsprachliche Bedeutungszuweisung, sondern die Etablierung phonologischer Repräsentationen maßgeblich ist. Ausgehend von diesen Ergebnissen wird ein differenziertes Schalenmodell der frühen phonologischen Entwicklung vorgestellt, nach welchem der segmentale Merkmalsausbau und seine Integration in die Silbe mittels Sonorität noch vor der metrischen Betonungszuweisung stattfindet. Unter Hinzunahme der Parallelen Architektur von Jackendoff (2002) wird abschließend eine kognitiv-linguistische Definition von Protowörtern gegeben, die nicht zuletzt auch zu diagnostischen Zwecken in der sprachtherapeutischen Praxis gebraucht werden kann.
Background: The European beech is arguably the most important climax broad-leaved tree species in Central Europe, widely planted for its valuable wood. Here, we report the 542 Mb draft genome sequence of an up to 300-year-old individual (Bhaga) from an undisturbed stand in the Kellerwald-Edersee National Park in central Germany.
Findings: Using a hybrid assembly approach, Illumina reads with short- and long-insert libraries, coupled with long Pacific Biosciences reads, we obtained an assembled genome size of 542 Mb, in line with flow cytometric genome size estimation. The largest scaffold was of 1.15 Mb, the N50 length was 145 kb, and the L50 count was 983. The assembly contained 0.12% of Ns. A Benchmarking with Universal Single-Copy Orthologs (BUSCO) analysis retrieved 94% complete BUSCO genes, well in the range of other high-quality draft genomes of trees. A total of 62,012 protein-coding genes were predicted, assisted by transcriptome sequencing. In addition, we are reporting an efficient method for extracting high-molecular-weight DNA from dormant buds, by which contamination by environmental bacteria and fungi was kept at a minimum.
Conclusions: The assembled genome will be a valuable resource and reference for future population genomics studies on the evolution and past climate change adaptation of beech and will be helpful for identifying genes, e.g., involved in drought tolerance, in order to select and breed individuals to adapt forestry to climate change in Europe. A continuously updated genome browser and download page can be accessed from beechgenome.net, which will include future genome versions of the reference individual Bhaga, as new sequencing approaches develop.
Heat stress transcription factors (Hsfs) are required for transcriptional changes during heat stress (HS) thereby playing a crucial role in the heat stress response (HSR). The target genes of Hsfs include heat shock proteins (Hsps), other Hsfs and genes involved in protection of the cell from irreversible damages due to exposure to elevated temperatures. Among 27 Hsfs in Solanum lycopersicum, HsfA1a, HsfA2 and HsfB1 constitute a functional triad which regulates important aspects of the HSR. HsfA1a is constitutively expressed and described as the master regulator of stress response and thermotolerance. Activation of HsfA1a under elevated temperatures leads to the induction of HsfA2 and HsfB1 which further stimulate the transcription of HS-responsive genes by forming highly active complexes with HsfA1a. Despite the well-established role of these three Hsfs in tomato HSR, information about functional relevance of other Hsfs is currently missing.
The heat stress inducible HsfA7 belongs alongside with HsfA2 to a phylogenetically distinct clade. Thereby the two proteins share high homology and a functional redundancy has been assumed. However, HsfA7 function and contribution to stress responses have not been investigated into detail in any plant species.
Tomato HsfA7 protein accumulates already at moderately elevated temperatures (~35°C) while HsfA2 becomes dominant at higher temperatures (>40°C). HsfA7 pre-mRNA undergoes complex and temperature-dependent alternative splicing resulting in several transcripts that encode for three protein isoforms. HsfA7-I contains a functional nuclear export signal (NES) and shows nucleocytoplasmic shuttling while HsfA7-II and HsfA7-III have a truncated NES which leads to the strong nuclear retention of the protein. Differences in the nucleocytoplasmic equilibrium have a major impact on the stability of protein isoforms, as nuclear retention is associated with increased protein turnover. Consequently, HsfA7-I shows a higher stability and can be detected even after 24 hours of stress attenuation, while HsfA7-II is rapidly degraded. The degradation of these factors is mediated by the ubiquitin-proteasome pathway.
HsfA7 can physically interact with HsfA1a and HsfA3 and form co-activator (“superactivator”) complexes with a very high transcriptional activity as shown on different HS-inducible promoters. In order for the complex to be successfully transferred to the nucleus and confer its activity it needs a functional nuclear localization signal (NLS) of HsfA7. In contrast, the activator (AHA) motif of HsfA7 is not essential for its co-activator function. Interestingly, while interaction of HsfA7 with either HsfA3 or HsfA1a stabilizes HsfA7 isoforms, concomitantly this leads to an increased turnover of HsfA1a and HsfA3. In contrast, HsfA2 has a stabilizing effect on the master regulator HsfA1a.
Thus, HsfA7 knockout mutants generated by CRISPR/Cas9 gene editing, show increased HsfA1a levels and a stronger induction of HS-related genes at 35°C compared to wild-type plants and HsfA2 knockout mutants. Consequently, HsfA7 knockout seedlings exhibit increased thermotolerance as shown by the enhanced hypocotyl elongation under a prolonged mild stress treatment at 35°C. In summary, these results highlight the importance of HsfA7 in regulation of cellular responses at elevated temperatures. Under moderately elevated temperatures, the accumulation of HsfA7 and its subsequent interaction with HsfA1a, leads to increased turnover of the latter, thereby ensuring a milder transcriptional activation of temperature-responsive genes like Hsps. In turn, in response to further elevated temperatures, HsfA2 becomes the dominant stress-induced Hsf. HsfA2 forms co-activator complexes with HsfA1a which in contrast to HsfA7, allows the stabilization of the master regulator, leading to the stronger expression of HS-responsive genes required for survival. Thereby, this study uncovers a new regulatory mechanism, where the temperature-dependent competitive interaction of HsfA2 and HsfA7 with HsfA1a control the fate of the master regulator and consequently the activity of temperature-responsive networks.
Widespread persistent inactivity makes continued efforts in physical activity promotion a persistent challenge. The precise content of physical activity recommendations is not broadly known, and there are concerns that the general messaging of the guidelines, including the recommendations to perform at least 150 min of at least moderate intensity physical activity per week might seem unattainable for and even actually discourage currently inactive people. Here we show that there are a myriad of ways of being physically active, and provide (in part) out-of-the-box examples of evidence based, pragmatic, easily accessible physical activity regimes below 150 min and/or with lower than moderate intensity that yield meaningful health benefits for currently inactive people.
Most of the elements heavier than iron are produced through neutron capture reactions in the s- and r -process. The overall path of the s-process is well understood and can be accurately reproduced in network simulations. However, there are still some neutron capture reactions of unstable nuclei involved in the s-process, which were not yet measured due to the difficulty in producing suitable targets. In those cases, theoretical models have to be used to estimate the missing cross section.
One example is the branching point nucleus 86Rb, whose neutron capture cross section cannot be directly measured due to its short half life of 18.86 days. It is, however, also possible to measure its inverse, the 87Rb(g,n) reaction in order to obtain the 86Rb(n,g) cross section through the principle of detailed balance.
Natural rubidium was irradiated with a quasi-monoenergetic photon beam in the energy range between 10.7 MeV and 16 MeV in order to investigate the photo-dissociation cross section of 87Rb. The results are presented in this thesis. Not only the total cross section of 87Rb(g,n), but also the partial production cross section of the ground and isomeric state of 84Rb through the 85Rb(g,n) reaction was measured.
Not all isotopes can be reached via neutron capture reaction, and are therefore bypassed by the s- and r -process. These 35 proton-rich isotopes are called p-nuclei and are produced in the γ-process by a chain of photo-disintegration reactions in Type II supernovae. Network calculations of Type II supernova show that the γ-process can explain the production of most p-nuclei, but some – especially 92/94Mo and 96/98Ru – are heavily underproduced. While this could be the result of deficiencies in the corresponding stellar models or insufficient knowledge of the involved reaction rates, it is also possible that the missing p-nuclei are synthesized in other production scenarios.
An alternative scenario for 92Mo is the production via a chain of proton capture reactions in Type Ia supernovae. One important reaction in this chain is the 90Zr(p,g) reaction. The reaction cross section was already measured several times, but the results were inconclusive. In the present work, the 90 Zr(p,g) reaction was measured using the in-beam gamma-ray spectroscopy technique and the discrepancies between the data sets could be largely explained.
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.
Background: The aim of this study was to investigate the acceptance and assessment of work shadowing carried out by students and dentists in dental practices. Furthermore, the extent to which students perceive an improvement in their specialised, communication and social competencies, was to be examined.
Methods: 61 dental students in their clinical semesters at a German university participated in work shadowing placements at 27 different general dental practices. Before beginning, they received checklists of various competencies that they self-assessed using school grades (from 1 = "very good", to 6 = "failed"), which they also repeated after completion. The dentists supplemented this with their external assessments. In addition, the students were requested to fill out a 54-item questionnaire and compose a freely-structured report after the work shadowing; the dentists filled out a questionnaire containing 16 items. The statistical analysis was carried out by means of the Friedman Test, including a post-hoc test (Bonferroni-Holm correction).
Results: The analysis showed a significant overall improvement in the students’ self-assessed competencies by 0.71* ± 0.43 grades. With an average of 0.33* ± 0.36, the dentists’ external assessment proved significantly higher than the self-assessment. The greatest improvements were perceived by the students in the areas of accounting (1.17* ± 0.77), practice organisation (1.05* ± 0.61) and dentist’s discussions (0.94* ±0.80) [*p < 0.05]. The students confirmed experiencing an expansion of knowledge, an improvement in their communication skills and indicated a high degree of satisfaction in regard to the dentists (school grade 1.58 ± 0.93). A maximum amount of satisfaction towards the work shadow students was demonstrated by the dentists, and this form of teaching was assessed with a school grade of 1.69 ± 0.89.
Conclusion: Both students and dental practitioners demonstrated a high level of satisfaction in regard to the work shadowing. The students felt their knowledge had increased, viewed the dentists as motivating role models and acknowledged a significant improvement in their specialised, communication and social competencies. Work shadowing in dental teaching practices presents a sensible addition to academic teaching at a university.
Immune-modulating therapy is a promising therapy for patients with cholangiocarcinoma (CCA). Microsatellite instability (MSI) might be a favorable predictor for treatment response, but comprehensive data on the prevalence of MSI in CCA are missing. The aim of the current study was to determine the prevalence of MSI in a German tertiary care hospital. Formalin-fixed paraffin-embedded tissue samples, obtained in the study period from 2007 to 2015 from patients with CCA undergoing surgical resection with curative intention at Johann Wolfgang Goethe University hospital, were examined. All samples were investigated immunohistochemically for the presence of MSI (expression of MLH1, PMS2, MSH2, and MSH6) as well as by pentaplex polymerase chain reaction for five quasimonomorphic mononucleotide repeats (BAT-25, BAT-26, NR-21, NR-22, and NR-24). In total, 102 patients were included, presenting intrahepatic (n = 35, 34.3%), perihilar (n = 42, 41.2%), and distal CCA (n = 25, 24.5%). In the immunohistochemical analysis, no loss of expression of DNA repair enzymes was observed. In the PCR-based analysis, one out of 102 patients was found to be MSI-high and one out of 102 was found to be MSI-low. Thus, MSI seems to appear rarely in CCA in Germany. This should be considered when planning immune-modulating therapy trials for patients with CCA.
Wenn man heute nach dem ideellen Vermächtnis Aby Warburgs fragt, kommen konzeptuell aufgeladene Begriffe, oder besser gesagt Denkfiguren, wie 'Pathosformel', 'Denkraum' und 'Mnemosyne' in den Sinn. Es sind geniale Wortschöpfungen, die längst jenseits der spezifischen Warburg-Forschung Eingang in die geisteswissenschaftliche Terminologie gefunden haben. Warburg selbst nun, wäre er nach dem für seine lebenslange Forschung zentralen Axiom gefragt worden, hätte zweifellos das 'Nachleben' oder 'Fortleben' oder den 'Einfluss der Antike' genannt. Die Ergründung dieses Phänomens, von ihm immer wieder als "Problem" bezeichnet, das ihn lebenslang "kommandierte", stand nicht nur im Zentrum seiner Forschung, sie war auch das Leitmotiv der Anschaffungspolitik und Organisation seiner Bibliothek – regelrecht sein Programm.
Der Kunst- und Kulturhistoriker Aby Warburg zählt zu den Ahnherren der Bildwissenschaft, die in Frankreich, Deutschland und den USA ihre wichtigsten Vertreterinnen und Vertreter hat. Er ist sogar ihr erster Wortführer in Methode und Programm gewesen. Sein Interesse galt nicht nur Kunstwerken, sondern Bildern und ihren Wirkungen überhaupt. Er analysierte Gemälde Botticellis und Manets ebenso wie Briefmarken und Plakate. Überall fand Warburg Gesten und Gebärden, in denen tiefste Trauer oder höchster Triumph ausgedrückt waren und die Szenen mörderischer Verfolgung oder schützender Sorge zeigten. In seinem Dürer-Vortrag von 1905 fand er dafür den Begriff "Pathosformel", in der psychische Energie gebunden sei und die "archäologisch getreu" nachgewiesen werden könne. Pathosformeln wurden zum Instrument seiner kulturgeschichtlich weit ausholenden Studien. Warburg zufolge ist in Pathosformeln seit der Antike der Weg darstellbar, der "aus dem stereometrisch gestaffelt gedachten Aufstiegsraum der Seele" – wie ihn die Mystiker aller Religionen kennen – zum "unendlichen Raum" führe, den er selbst den "mathematischen und psychotechnischen Denkraum" nannte. Er hat ihn auf der dritten der programmatischen Tafeln des Bilderatlasses dargestellt. Dieser Weg war für ihn gleichbedeutend mit der Befreiung des Menschen aus Dämonenfurcht und Sternenglauben, aus Abhängigkeit und Angst. Endlich los kommen müssen wir (so Warburgs Appell) von der dämonischen Seite der heidnischen Götter, die die Rückenansicht ihrer olympischen Heiterkeit ist! In ihnen seien Logik und Magie vereint, die sich "wie Tropus und Metapher" verhielten, die "auf einem Stamme geimpfet blühten ". Warburg suchte nach dem unklassischen, weil ganz auf die Gegenwart bezogenen Nachleben der Antike in Wort und Bild.
Pünktlich zum Abschluss des 'Historischen Wörterbuchs der Philosophie' flackerte eine Kontroverse um die Beziehung zwischen seinem Begründer und ersten Herausgeber Joachim Ritter und dessen Münsteraner Lehrstuhlnachfolger Hans Blumenberg auf. Den Ausgangspunkt bildete die theoretisch-methodologische Frage der Verhältnisbestimmung von Begriff und Metapher bzw. Begriffsgeschichte und Metaphorologie, an die sich jedoch zumindest andeutungsweise auch biographisch und wissenschaftshistorisch ausgerichtete Erwägungen anschlossen.
Wie verhalten sich historische Textsemantik und bildsprachliche Semantik zueinander? Welche strukturellen Gemeinsamkeiten bzw. Unterschiede bestehen zwischen politischen Grundbegriffen und ihren Visualisierungen? Wie verändern sie sich in der 'Sattelzeit', an der Schwelle zur Moderne? Diesen Fragen versucht der folgende Essay nicht theoretisch, sondern empirisch anhand eines französischen Fallbeispiels nachzuspüren: der Ikonographie von République in der Zeit von 1789 bis 1889. Die exemplarischen Bildbelege entstammen der zeitgenössischen Gebrauchsgrafik, einem Printmedium relativ großer sozialer Reichweite, gesammelt im Fundus des Lexikons der Revolutions-Ikonographie. Begriffshistorische Vergleichsmöglichkeiten bietet u. a. das Handbuch politisch-sozialer Grundbegriffe in Frankreich.
Es geht im Folgenden darum, nach Berührungspunkten und Unterschieden zwischen Kosellecks Zugang und dem Warburgs zu fragen. Dies erfolgt in einer – selbstverständlich nur sehr ausschnitthaften, auf einige methodische Grundannahmen beschränkten – parallelen Lektüre, die Kosellecks und Warburgs Verständnis bildlicher und begrifflicher Semantiken und der Bedeutung von Epochenschwellen für deren Wandel zueinander in Beziehung setzt. Das durch die Tagung thematisierte Spannungsfeld "Bild – Begriff – Epoche" würde sich zu einer sehr viel umfassenderen und über diese beiden Autoren hinausgehenden Bestandsaufnahme eignen, um Parallelen, Bezugnahmen und Unterschiede zwischen Begriffsgeschichtsforschung und (politischer) Ikonologie, zwischen dem Projekt der Geschichtlichen Grundbegriffe und den Forschungsprogrammen an der Kulturwissenschaftlichen Bibliothek Warburg (KBW) zu untersuchen.
Koselleck has repeatedly rejected the existence of a collective memory. All memory derives from individual experiences which are not interchangeable. Any person has the right to his own memories, without which he could not live and which cannot be collectivized. Only the conditions under which they are realized and recollected may be referred to as supra-individual. For this reason it is advisable to distinguish between the primary experiences of those who have lived them as a first person and who bind them to their own memories, and the secondary experiences after the fact of those who were not present in the situation which gave rise to the immediate experience. This distinction also applies to memorials. The messages of monuments are open to a double exegesis: they evoke the unmistakable occasions that have led to death. Like primary experiences they are not interchangeable. But, even so, artistic responses to incomparable occasions repeat themselves. There is only a limited repertoire of aesthetic solutions for fixating violent death – which individually is always unique – in the memory.
Das Denken der 'neuen' Form setzt sich bei Cassirer aus der rationalen und der sinnlichen Erkenntnis zusammen. Den Formbegriff der rationalen Erkenntnis gewinnt er mithilfe der Philosophie, den der sinnlichen Erkenntnis aus der Kunst. Ist für ersteren vor allem Leibniz wichtig geworden, beruft er sich bei letzterem explizit auf Goethe. Im Folgenden werde ich versuchen, beide Erkenntnisweisen nachzuvollziehen, um die These herzuleiten, dass Cassirer keine Hierarchisierung zwischen Begriff und Bild vornimmt.
Einführung
(2018)
Warburg wirkte auch über den engeren Kreis der Kulturwissenschaftlichen Bibliothek Warburg hinaus. Mit Walter Benjamins Werk, Franz Dornseiffs Onomasiologie oder Ernst Robert Curtius' an das 'Nachleben der Antike' anknüpfender 'historischer Topik' seien nur einige der Arbeiten über Sprache genannt, die von Warburgs kunstwissenschaftlichen Ideen inspiriert waren. Insbesondere Curtius' Arbeiten – und das berührt unsere Frage nach der Epochenschwelle – sind dabei als Ansatz wahrgenommen worden, überhistorische Denkfiguren und geistesgeschichtliche Kontinuitäten gegen die Gefahr des Historismus und von Brüchen im Traditionszusammenhang aufzuzeigen und damit Warburgs 1912 in Rom verkündetes Programm aufzunehmen, durch "ikonologische Analyse", die sich durch grenzpolitische Befangenheit nicht davor abschrecken lässt, Antike, Mittelalter und Neuzeit als zusammenhängende Epoche anzusehen.
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'.
In der rezensierten Monographie gelingt es, "New Public Management" als strategisches und politisches Projekt auszudeuten. Die Konsequenzen für die Liegenschaftspolitik können fundiert dargelegt werden. In der Rezension wird eine Einordnung in die bisherige Forschung sowie eine kritische Würdigung der rezensierten Arbeit versucht.
In mammalian species, including humans, the hippocampal dentate gyrus (DG) is a primary region of adult neurogenesis. Aberrant adult hippocampal neurogenesis is associated with neurological pathologies. Understanding the cellular mechanisms controlling adult hippocampal neurogenesis is expected to open new therapeutic strategies for mental disorders. Microglia is intimately associated with neural progenitor cells in the hippocampal DG and has been implicated, under varying experimental conditions, in the control of the proliferation, differentiation and survival of neural precursor cells. But the underlying mechanisms remain poorly defined. Using fluorescent in situ hybridization we show that microglia in brain express the ADP-activated P2Y13 receptor under basal conditions and that P2ry13 mRNA is absent from neurons, astrocytes, and neural progenitor cells. Disrupting P2ry13 decreases structural complexity of microglia in the hippocampal subgranular zone (SGZ). But it increases progenitor cell proliferation and new neuron formation. Our data suggest that P2Y13 receptor-activated microglia constitutively attenuate hippocampal neurogenesis. This identifies a signaling pathway whereby microglia, via a nucleotide-mediated mechanism, contribute to the homeostatic control of adult hippocampal neurogenesis. Selective P2Y13R antagonists could boost neurogenesis in pathological conditions associated with impaired hippocampal neurogenesis.
How demanding and consistent is the 2018 stress test design in comparison to previous exercises?
(2018)
Bank regulators have the discretion to discipline banks by executing enforcement actions to ensure that banks correct deficiencies regarding safe and sound banking principles. We highlight the trade-offs regarding the execution of enforcement actions for financial stability. Following this we provide an overview of the differences in the legal framework governing supervisors’ execution of enforcement actions in the Banking Union and the United States. After discussing work on the effect of enforcement action on bank behaviour and the real economy, we present data on the evolution of enforcement actions and monetary penalties by U.S. regulators. We conclude by noting the importance of supervisors to levy efficient monetary penalties and stressing that a division of competences among different regulators should not lead to a loss of efficiency regarding the execution of enforcement actions.
A new governance architecture for european financial markets? Towards a european supervision of CCPs
(2018)
Does the new European outlook on financial markets, as voiced by the EU Commission since the beginning of the Capital Market Unions imply a movement of the EU towards an alignment of market integration and direct supervision of common rules? This paper sets out to answer this question for the case of common supervision for Central Counterparties (CCPs) in the European Union. Those entities gained crucial importance post-crisis due to new regulation which requires the mandatory clearing of standardized derivative contracts, transforming clearing houses into central nodes for cross-border financial transactions. While the EU-wide regulatory framework EMIR, enacted in 2012, stipulates common regulatory requirements, the framework still relies on home-country supervision of those rules, arguably leading to regulatory as well as supervisory arbitrage. Therefore, the regulatory reform to stabilize the OTC derivatives market replicated at its center a governance flaw, which had been identified as one of the major causes for the gravity of the financial crisis in the EU: the coupling of intense competition based on private risk management systems with a national supervision of European rules. This paper traces the history of this problem awareness and inquires which factors account for the fact that only in 2017 serious negotiations at the EU level ensued that envisioned a common supervision of CCPs to fix the flawed system of governance. Analyzing this shift in the European governance architecture, we argue that Brexit has opened a window of opportunity for a centralization of supervision for CCPs. Brexit aligns the urgency of the problem with material interests of crucial political stakeholder, in particular of Germany and France, providing the possibility for a grand European bargain.
Improving financial conditions of individuals requires an understanding of the mechanisms through which bad financial decision-making leads to worse financial outcomes. From a theoretical point of view, a key candidate inducing mistakes in financial decision-making are so called present-biased preferences, which are one of the cornerstones of behavioral economics. According to theory, present-biased households should behave systematically different when it comes to consumption and saving decisions, as they should be more prone to spending too much and saving too little.
In this policy letter we show how high frequency financial transaction data available in digitized form allows to precisely categorize individual financial-decision making to be present-biased or not. Using this categorization, we find that one out of five individuals in our sample exhibits present-bias and that this present-biased behavior is associated with a stronger use of overdrafts. As overdrafts represent a particularly expensive way of short-term borrowing, their systematic use can be interpreted as a measure of suboptimal financial-decision making. Overall, our results indicate that the combination of economic theory and Big Data is able to generate valuable insights with applications for policy makers and businesses alike.
This paper presents an imaging radar system for structural health monitoring (SHM) of wind turbine blades. The imaging radar system developed here is based on two frequency modulated continuous wave (FMCW) radar sensors with a high output power of 30 dBm. They have been developed for the frequency bands of 24,05 GHz-24,25 GHz and 33.4 GHz-36.0 GHz, respectively. Following the successful proof of damage detection and localization in laboratory conditions, we present here the installation of the sensor system at the tower of a 2 MW wind energy plant at 95 m above ground. The realization of the SHM-system will be introduced including the sensor system, the data acquisition framework and the signal processing procedures. We have achieved an imaging of the rotor blades using inverse synthetic aperture radar techniques under changing environmental and operational condition. On top of that, it was demonstrated that the front wall and back wall radar echo can be extracted from the measured signals demonstrating the full penetration of wind turbine blades during operation.
Dysregulation of blood sphingolipids is an emerging topic in clinical science. The objective of this study was to determine preanalytical biases that typically occur in clinical and translational studies and that influence measured blood sphingolipid levels. Therefore, we collected blood samples from four healthy male volunteers to investigate the effect of storage conditions (time, temperature, long-term storage, freeze–thaw cycles), blood drawing (venous or arterial sampling, prolonged venous compression), and sample preparation (centrifugation, freezing) on sphingolipid levels measured by LC-MS/MS. Our data show that sphingosine 1-phosphate (S1P) and sphinganine 1-phosphate (SA1P) were upregulated in whole blood samples in a time- and temperature-dependent manner. Increased centrifugation at higher speeds led to lower amounts of S1P and SA1P. All other preanalytical biases did not significantly alter the amounts of S1P and SA1P. Further, in almost all settings, we did not detect differences in (dihydro)ceramide levels. In summary, besides time-, temperature-, and centrifugation-dependent changes in S1P and SA1P levels, sphingolipids in blood remained stable under practically relevant preanalytical conditions.
Innerhalb der Gentrifizierungsforschung analysiert die Rent‑Gap‑Theorie, wie kleinräumige Differenzen zwischen gegenwärtigen Verwertungsbedingungen einerseits sowie Erwartungen auf zukünftig steigende Mieten andererseits Verdrängungsprozesse antreiben. Dementgegen hat Eric Clark (2014) jüngst eingefordert, dass die Stadtforschung den Blick verstärkt darauf richten müsse, wie Verdrängung verhindert werden kann. Diesen Appell aufgreifend, zeigen wir bezogen auf den deutschen Kontext, inwiefern mietrechtliche Regularien, stadtplanerische Entscheidungen und die jeweilige Eigentümerstruktur wesentlich darüber entscheiden, ob sich ein immobilienwirtschaftlicher Verwertungsdruck auch tatsächlich in Verdrängungsprozesse übersetzt. Illustriert wird dies am Wandel der Eigentümerstruktur im Frankfurter Gallus seit den 1970er Jahren. Deutlich wird dabei, dass Gentrifizierung kein Naturgesetz darstellt, sondern ein zutiefst politischer Prozess ist, der sich effektiv verhindern lässt.
Far outside the surface of slabs, the exact exchange (EXX) potential vx falls off as −1/z , if z denotes the direction perpendicular to the surface and the slab is localized around z=0 . Similarly, the EXX energy density ex behaves as −n/(2z) , where n is the electron density. Here, an alternative proof of these relations is given, in which the Coulomb singularity in the EXX energy is treated in a particularly careful fashion. This new approach allows the derivation of the next-to-leading order contributions to the asymptotic vx and ex . It turns out that in both cases, the corrections are proportional to 1/z2 in general.
Acute graft-versus-host disease (GvHD) is still a major cause of treatment-related mortality after allogeneic stem cell transplantation. Allo-antigen recognition of donor T cells after transplantation account for the onset and persistence of this disease. MicroRNAs (miRNAs) are molecular regulators involved in numerous processes during T-cell development, homeostasis, and activation. Thus, miRNAs also contribute to pathological T-cell function during GvHD. Given their capacity of fine-tuning T-cell function, miRNAs have emerged as promising therapeutic targets to curtail acute GvHD, but simultaneously maintain T-cell-mediated graft-versus-tumor effects. Here, we review the role of key miRNAs contributing to the pathophysiology of GvHD. We focus on those miRNAs acting in T cells and for which a role in GvHD has been established in preclinical models. Finally, we provide an outlook for clinical application of this new therapeutic target for GvHD prevention and treatment.
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.
The bile acid activated transcription factor farnesoid X receptor (FXR) regulates numerous metabolic processes and is a rising target for the treatment of hepatic and metabolic disorders. FXR agonists have revealed efficacy in treating non-alcoholic steatohepatitis (NASH), diabetes and dyslipidemia. Here we characterize imatinib as first-in-class allosteric FXR modulator and report the development of an optimized descendant that markedly promotes agonist induced FXR activation in a reporter gene assay and FXR target gene expression in HepG2 cells. Differential effects of imatinib on agonist-induced bile salt export protein and small heterodimer partner expression suggest that allosteric FXR modulation could open a new avenue to gene-selective FXR modulators.
An empirical study of the per capita yield of science Nobel prizes : is the US era coming to an end?
(2018)
We point out that the Nobel prize production of the USA, the UK, Germany and France has been in numbers that are large enough to allow for a reliable analysis of the long-term historical developments. Nobel prizes are often split, such that up to three awardees receive a corresponding fractional prize. The historical trends for the fractional number of Nobelists per population are surprisingly robust, indicating in particular that the maximum Nobel productivity peaked in the 1970s for the USA and around 1900 for both France and Germany. The yearly success rates of these three countries are to date of the order of 0.2–0.3 physics, chemistry and medicine laureates per 100 million inhabitants, with the US value being a factor of 2.4 down from the maximum attained in the 1970s. The UK in contrast managed to retain during most of the last century a rate of 0.9–1.0 science Nobel prizes per year and per 100 million inhabitants. For the USA, one finds that the entire history of science Noble prizes is described on a per capita basis to an astonishing accuracy by a single large productivity boost decaying at a continuously accelerating rate since its peak in 1972.
The theory and practice of urban governance in recent years has undergone both a collaborative and participatory turn. The strong connection between collaboration and participation has meant that citizen participation in urban governance has been conceived in a very particular way: as varying levels of partnership between state actors and citizens. This over-focus on collaboration has led to: 1) a dearth of proposals in theory and practice for citizens to engage oppositionally with institutions; 2) the miscasting of agonistic opportunities for participation as forms of collaboration; 3) an inability to recognise the irruption of agonistic practices into participatory procedures. This article attempts to expand the conception of participatory urban governance by adapting Rosanvallon’s (2008) three democratic counter-powers—prevention, oversight and judgement—to consider options for institutionalising agonistic participatory practices. It argues that these counter-governance processes would more fully realise the inclusion agenda that underpins the participatory governance project.
By the fabrication of periodically arranged nanomagnetic systems it is possible to engineer novel physical properties by realizing artificial lattice geometries that are not accessible via natural crystallization or chemical synthesis. This has been accomplished with great success in two dimensions in the fields of artificial spin ice and magnetic logic devices, to name just two. Although first proposals have been made to advance into three dimensions (3D), established nanofabrication pathways based on electron beam lithography have not been adapted to obtain free-form 3D nanostructures. Here we demonstrate the direct-write fabrication of freestanding ferromagnetic 3D nano-architectures. By employing micro-Hall sensing, we have determined the magnetic stray field generated by our free-form structures in an externally applied magnetic field and we have performed micromagnetic and macro-spin simulations to deduce the spatial magnetization profiles in the structures and analyze their switching behavior. Furthermore we show that the magnetic 3D elements can be combined with other 3D elements of different chemical composition and intrinsic material properties.
Fluctuation spectroscopy measurements of quasi-two-dimensional organic charge-transfer salts (BEDT-TTF) 2 X are reviewed. In the past decade, the method has served as a new approach for studying the low-frequency dynamics of strongly correlated charge carriers in these materials. We review some basic aspects of electronic fluctuations in solids, and give an overview of selected problems where the analysis of 1/f -type fluctuations and the corresponding slow dynamics provide a better understanding of the underlying physics. These examples are related to (1) an inhomogeneous current distribution due to phase separation and/or a percolative transition; (2) slow dynamics due to a glassy freezing either of structural degrees of freedom coupling to the electronic properties or (3) of the electrons themselves, e.g., when residing on a highly-frustrated crystal lattice, where slow and heterogeneous dynamics are key experimental properties for the vitrification process of a supercooled charge-liquid. Another example is (4), the near divergence and critical slowing down of charge carrier fluctuations at the finite-temperature critical endpoint of the Mott metal-insulator transition. Here also indications for a glassy freezing and temporal and spatial correlated dynamics are found. Mapping out the region of ergodicity breaking and understanding the influence of disorder on the temporal and spatial correlated fluctuations will be an important realm of future studies, as well as the fluctuation properties deep in the Mott or charge-ordered insulating states providing a connection to relaxor or ordered ferroelectric states studied by dielectric spectroscopy.
Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile.
The prediction of protein–ligand interactions and their corresponding binding free energy is a challenging task in structure-based drug design and related applications. Docking and scoring is broadly used to propose the binding mode and underlying interactions as well as to provide a measure for ligand affinity or differentiate between active and inactive ligands. Various studies have revealed that most docking software packages reliably predict the binding mode, although scoring remains a challenge. Here, a diverse benchmark data set of 99 matched molecular pairs (3D-MMPs) with experimentally determined X-ray structures and corresponding binding affinities is introduced. This data set was used to study the predictive power of 13 commonly used scoring functions to demonstrate the applicability of the 3D-MMP data set as a valuable tool for benchmarking scoring functions.
Background: Immigration has a strong impact on the development of health systems, medicine and science worldwide. Therefore, this article provides a descriptive study on the overall research output.
Methods: Utilizing the scientific database Web of Science, data research was performed. The gathered bibliometric data was analyzed using the established platform NewQIS, a benchmarking system to visualize research quantity and quality indices.
Findings: Between 1900 and 2016 a total of 6763 articles on immigration were retrieved and analyzed. 86 different countries participated in the publications. Quantitatively the United States followed by Canada and Spain were prominent regarding the article numbers. On comparing by additionally taking the population size into account, Israel followed by Sweden and Norway showed the highest performance. The main releasing journals are the Public Health Reports, the Journal of Immigrant and Minority Health and Social Science & Medicine. Over the decades, an increasing number of Public, Environmental & Occupational Health articles can be recognized which finally forms the mainly used subject area.
Conclusion: Considerably increasing scientific work on immigration cannot only be explained by the general increase of scientific work but is also owed to the latest development with increased mobility, worldwide crises and the need of flight and migration. Especially countries with a good economic situation are highly affected by immigrants and prominent in their publication output on immigration, since the countries’ publication effort is connected with the appointed expenditures for research and development. Remarkable numbers of immigrants throughout Europe compel medical professionals to consider neglected diseases, requires the public health system to restructure itself and finally promotes science.
The HCV NS5A protein plays multiple roles during viral replication, including viral genome replication and virus particle assembly. The crystal structures of the NS5A N-terminal domain indicated the potential existence of the NS5A dimers formed via at least two or more distinct dimeric interfaces. However, it is unknown whether these different forms of NS5A dimers are involved in its numerous functions. To address this question, we mutated the residues lining the two different NS5A dimer interfaces and determined their effects on NS5A self-interaction, NS5A-cyclophilin A (CypA) interaction, HCV RNA replication and infectious virus production. We found that the mutations targeting either of two dimeric interfaces disrupted the NS5A self-interaction in cells. The NS5A dimer-interrupting mutations also inhibited both viral RNA replication and infectious virus production with some genotypic differences. We also determined that reduced NS5A self-interaction was associated with altered NS5A-CypA interaction, NS5A hyperphosphorylation and NS5A subcellular localization, providing the mechanistic bases for the role of NS5A self-interaction in multiple steps of HCV replication. The NS5A oligomers formed via different interfaces are likely its functional form, since the residues at two different dimeric interfaces played similar roles in different aspects of NS5A functions and, consequently, HCV replication. In conclusion, this study provides novel insight into the functional significance of NS5A self-interaction in different steps of the HCV replication, potentially, in the form of oligomers formed via multiple dimeric interfaces.
The NF-κB-like velvet domain protein VosA (viability of spores) binds to more than 1,500 promoter sequences in the filamentous fungus Aspergillus nidulans. VosA inhibits premature induction of the developmental activator gene brlA, which promotes asexual spore formation in response to environmental cues as light. VosA represses a novel genetic network controlled by the sclB gene. Bfunction is antagonistic to VosA, because it induces the expression of early activator genes of asexual differentiation as flbC and flbD as well as brlA. The SclB controlled network promotes asexual development and spore viability, but is independent of the fungal light control. SclB interactions with the RcoA transcriptional repressor subunit suggest additional inhibitory functions on transcription. SclB links asexual spore formation to the synthesis of secondary metabolites including emericellamides, austinol as well as dehydroaustinol and activates the oxidative stress response of the fungus. The fungal VosA-SclB regulatory system of transcription includes a VosA control of the sclB promoter, common and opposite VosA and SclB control functions of fungal development and several additional regulatory genes. The relationship between VosA and SclB illustrates the presence of a convoluted surveillance apparatus of transcriptional control, which is required for accurate fungal development and the linkage to the appropriate secondary metabolism.
This thesis investigates whether professionals on the global financial markets, such as investment bankers, traders, and analysts, form a global social class.
Over recent decades, rising inequality has reinvigorated interest in issues of class. Despite the experience of world-wide economic crises demonstrating the global reach of the contemporary economy, the research areas of globalisation and class remain surprisingly disengaged from each other. Especially the question of global class formation remains underexplored.
The first part of this thesis examines why the issue of globalisation remains a niche within research on class. Therefore, the theoretical foundations of the dominant approaches to class are investigated, identifying the causes for the implicit “methodological nationalism” of modern mainstream class analysis in the underlying theories of the economy and social action. Vice-versa, an examination of globalisation theory shows that similar obstacles persist in the theoretical reasoning on inequality from a global perspective, precluding a conceptualisation of global class formation. In dialogue with the few existing approaches to conceptualize class on a global level, a framework for the study of global class formation based on Pierre Bourdieu’s notion of social fields is developed.
In part two of the thesis this framework is employed to examine empirically, whether the global field of finance is currently the source for the formation of a global financial class. The field of finance as the most globalised economic sector is a paradigmatic case for studying the formation of a global class. An interview study on the career trajectories of financial professionals from Frankfurt and Sydney uncovers that despite the legacy of national economic specificities on the institutional level, financial actors draw in their social praxis on global forms of social, cultural, and economic capital and have developed a common culture, worldview, praxis, and habitus, delineating the formation of a global financial class.
Five new species belonging to Hermatomyces (Hermatomycetaceae, Pleosporales) are described based on morphological investigations of specimens collected on rotten twigs and stems of various plants in Panama as well as phylogenetic analyses of sequence data of nuclear ribosomal and protein coding genes (EF1-α, RPB2, β-TUB). The new species are described as: Hermatomyces bifurcatus, H. constrictus, H. megasporus, H. sphaericoides, and H. verrucosus spp. nov. Previously described species such as H. sphaericus and H. tucumanensis were identified among the studied specimens. The new combination, H. reticulatus, is made for Subicularium reticulatum based on examination of the holotype and fresh collections. Hermatomyces subiculosus, originally described from Thailand, is reduced to synonymy with H. reticulatus; H. tectonae is synonymized under H. sphaericus based on morphological and molecular evidence; and H. chiangmaiensis and H. thailandicus are considered later synonyms of H. krabiensis and H. indicus, respectively. The type material of Scyphostroma mirum was found to be conspecific with H. tucumanensis and, therefore, the generic name Hermatomyces should be conserved or protected against the older name Scyphostroma and the binomial H. tucumanensis against S. mirum. Sixteen species of Hermatomyces are recognized, their distinctive characteristics are highlighted in line drawings and a key is provided for their identification. The peculiar morphology and consistent phylogeny of new and previously known Hermatomyces species supports the recognition of the recently introduced monotypic family Hermatomycetaceae as a well delimited monophyletic taxon within the order Pleosporales.
Leaf-stripe smuts on grasses are a highly polyphyletic group within Ustilaginomycotina, occurring in three genera, Tilletia, Urocystis, and Ustilago. Currently more than 12 Ustilago species inciting stripe smuts are recognised. The majority belong to the Ustilago striiformis-complex, with about 30 different taxa described from 165 different plant species. This study aims to assess whether host distinct-lineages can be observed amongst the Ustilago leaf-stripe smuts using nine different loci on a representative set. Phylogenetic reconstructions supported the monophyly of the Ustilago striiformis-complex that causes leaf-stripe and the polyphyly of other leaf-stripe smuts within Ustilago. Furthermore, smut specimens from the same host genus generally clustered together in well-supported clades that often had available species names for these lineages. In addition to already-named lineages, three new lineages were observed, and described as new species on the basis of host specificity and molecular differences: namely Ustilago jagei sp. nov. on Agrostis stolonifera, U. kummeri sp. nov. on Bromus inermis, and U. neocopinata sp. nov. on Dactylis glomerata.
Background: Recent epidemics have entailed global discussions on revamping epidemic control and prevention approaches. A general consensus is that all sources of data should be embraced to improve epidemic preparedness. As a disease transmission is inherently governed by individual-level responses, pathogen dynamics within infected hosts posit high potentials to inform population-level phenomena. We propose a multiscale approach showing that individual dynamics were able to reproduce population-level observations.
Methods: Using experimental data, we formulated mathematical models of pathogen infection dynamics from which we simulated mechanistically its transmission parameters. The models were then embedded in our implementation of an age-specific contact network that allows to express individual differences relevant to the transmission processes. This approach is illustrated with an example of Ebola virus (EBOV).
Results: The results showed that a within-host infection model can reproduce EBOV’s transmission parameters obtained from population data. At the same time, population age-structure, contact distribution and patterns can be expressed using network generating algorithm. This framework opens a vast opportunity to investigate individual roles of factors involved in the epidemic processes. Estimating EBOV’s reproduction number revealed a heterogeneous pattern among age-groups, prompting cautions on estimates unadjusted for contact pattern. Assessments of mass vaccination strategies showed that vaccination conducted in a time window from five months before to one week after the start of an epidemic appeared to strongly reduce epidemic size. Noticeably, compared to a non-intervention scenario, a low critical vaccination coverage of 33% cannot ensure epidemic extinction but could reduce the number of cases by ten to hundred times as well as lessen the case-fatality rate.
Conclusions: Experimental data on the within-host infection have been able to capture upfront key transmission parameters of a pathogen; the applications of this approach will give us more time to prepare for potential epidemics. The population of interest in epidemic assessments could be modelled with an age-specific contact network without exhaustive amount of data. Further assessments and adaptations for different pathogens and scenarios to explore multilevel aspects in infectious diseases epidemics are underway.
In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α). Knockdown of TKTL1 via shRNA increased the cells’ demand for glucose, decreased flux through the PPP and promoted cell death under hypoxic conditions. Following irradiation, suppression of TKTL1 expression resulted in elevated levels of reactive oxygen species (ROS) and reduced clonogenic survival. In summary, our results indicate a role of TKTL1 in the adaptation of tumor cells to oxygen deprivation and in the acquisition of radioresistance. Further studies are necessary to examine whether strategies that antagonize TKTL1 function will be able to restore the sensitivity of glioma cells towards irradiation and antiangiogenic therapies in the more complex in vivo environment.
Cardiac sarcoidosis is a rare immunologic disease causing heart involvement in 5% of patients. Cardiac sarcoidosis may manifest clinically as a cardiomyopathy with impaired left ventricular (LV) function or as tachyarrhythmias or bradyarrhythmias. On autopsy, cardiac granulomas can be found in approximately 25% of patients. The most common location for granulomas and scars is the LV free wall, followed by the intraventricular septum, often with involvement of the conduction system. ...
Temperature- and field-dependent 1H-, 19F-, and 79,81Br-NMR measurements together with zero - field 79,81Br-NQR measurements on polycrystalline samples of barlowite, Cu4(OH)6FBr are conducted to study the magnetism and possible structural distortions on a microscopic level. The temperature dependence of the 79,81Br-NMR spin-lattice relaxation rates 1/T1 indicate a phase transition at TN ≃ 15 K which is of magnetic origin, but with an unusually weak slowing down of fluctuations below TN. Moreover, 1/T1T scales linear with the bulk susceptibility which indicates persisting spin fluctuations down to 2 K. Quadupolare resonance (NQR) studies reveal a pair of zero-field NQR- lines associated with the two isotopes of Br with the nuclear spins of I = 3/2. Quadrupole coupling constants of vQ ≃ 28.5 MHz and 24.7 MHz for 79Br- and 81Br-nuclei are determined from Br-NMR and the asymmetry parameter of the electric field gradient was estimated to η ≃ 0.2. The Br-NQR lines are consistent with our findings from Br-NMR and they are relatively broad, even above TN. This broadening and the relative large η value suggests a symmetry reduction at the Br- site reflecting the presence of a local distortion in the lattice. Our density-functional calculations show that the displacements of Cu2 atoms located between the kagome planes do not account for this relatively large η. On the other hand, full structural relaxation, including the deformation of kagome planes, leads to a better agreement with the experiment.