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Dezember 1925, Staatsoper Unter den Linden Berlin: Zwei Tage vor Weihnachten besuchen Theodor W. Adorno und Walter Benjamin die erste auf die aufsehenerregende Uraufführung folgende Vorstellung von Alban Bergs Oper Wozzeck: Es dirigiert Erich Kleiber, die Hauptpartien singen Leo Schützendorf, Fritz Soot und Sigrid Johanson. Nicht nur auf den 'Expertenhörer' Adorno - der in einem an seinen Kompositionslehrer übermittelten Bericht sowohl Benjamins Bestimmung des "Ausdruckslosen" aufgreift, als auch dessen physische Präsenz erwähnt - hinterlässt die Musik einen bleibenden Eindruck. Benjamin erinnert sich dieser Aufführung noch zehn Jahre später in einem seiner Briefe an Adorno und bekennt nach der Lektüre von dessen Berg-Analysen, "dass der überwältigende Eindruck, kraft dessen mich der Wozzeck an jenem Abend gefangen nahm, das Signal eines mir unbewussten aber bis ins einzelne nennbaren Betroffenseins gewesen ist". Von der geschichtsphilosophischen Einordnung der Berg'schen Musik, welche "wie die gleichsam namenlose technische Arbeit des Schülers Schönbergs die Tradition des 19ten Jahrhunderts im Namen des Musikers zur Ruhe geleitet und ihren eigenen Klagegesang anstimmen lässt", führt Benjamin sich dann sogar versucht, den "Begriff des 'kleinen Übergangs' [...] der Kompositionslehre abzuborgen (GB V, 565). Im Gegensatz zu Adorno wird Walter Benjamins Theorie jedoch kaum mit Musik in Verbindung gebracht, sondern vor allem für ihr Bilddenken geschätzt. Auch wenn im 'Ursprung des Deutschen Trauerspiels', in den Erinnerungsszenen der 'Berliner Kindheit', den Häuser- und Gedankenschluchten der 'Passagenarbeit' und nicht zuletzt in seinem Briefwechsel durchaus von Musik die Rede ist, rücken Klänge seltener in den Mittelpunkt seiner Schriften und sind in der Rezeption bisher auch weniger beachtet worden. Ohnedies wird derjenige enttäuscht, der gerade von Benjamin - so reizvoll es sein mag, sich solchen Gegenständen widmende Essays zu imaginieren - die Exegese des gängigen musikalischen Kanons erwartet: Keine Abhandlung zu Schuberts Streichquintett schließt an die Interpretation der 'Wahlverwandschaften' an und ebenso vergeblich sucht man nach die Erwägungen zum Trauerspiel auf die Affektkontrolle der 'opera seria' oder die des Kraus-Essays auf die Musik des 'Fackel'-Habitués Arnold Schönberg übertragenden Arbeiten. Dennoch kommt Musik, Klage und Tönen in Benjamins Reflexionen eine nicht unerhebliche Bedeutung zu. Selten drängen sie sich lautstark in den Vordergrund, erlauben aber - zumal in einer Zeit, in der auch die professionelle Auseinandersetzung mit Musik die ideale Beständigkeit musikalischer Werke und ihrer Texte zunehmend in Zweifel zieht - theoretische Einsichten, über die das auf andere Dinge gerichtete Ohr des Experten achtlos hinweggeht. In Ergänzung zur wohlbekannten epistemischen und poetischen Rolle seiner Sprach- und Denkbilder unternimmt dieser Band den ersten systematisch angelegten Versuch, sowohl den kultur- und medienhistorischen Zusammenhängen von Benjamins akustischen Motiven nachzugehen als auch ihre ästhetische Relevanz für die gegenwärtige Produktion und Reproduktion von Klängen zu reflektieren.
'The Making of Americans' wurde 1903 begonnen, 1905/6 zugunsten des Erzählbands 'Three Lives' unterbrochen, 1906 und 1908 komplett umgeschrieben und 1911 schließlich abgeschlossen (also viel früher als 'Ulysses' und 'À la recherche du temps perdu'). Zur Veröffentlichung des Romans kam es allerdings erst 1925, was die öffentliche Wahrnehmung des Textes als einer Urszene der Moderne stark beeinträchtigt hat. Aber es gibt auch noch andere Gründe, weshalb 'The Making of Americans' rasch in Vergessenheit geriet: der riesige Umfang des Romans (fast 1000 Seiten) und seine serielle Wiederholungsstruktur sorgten dafür, dass er einer größeren Leseöffentlichkeit bis heute weitgehend unbekannt blieb. Steins Aufkündigung der Erzähltradition des 19. Jahrhunderts fiel noch radikaler aus als Prousts und Joyces Romanexperimente. Es gibt aber durchaus Gemeinsamkeiten: alle drei Autoren machen die Prozesse des Erinnerns, Denkens und Fühlens zur Grundlage der Darstellung im Roman und verzichten auf die teleologische Konsequenz kausaler Verknüpfungen zugunsten des verdichteten Augenblicks. Schon im ursprünglichen Entwurf von 'The Making of Americans', der auf den ersten Seiten des Romans noch erkennbar ist, sind erste Anzeichen für den Bruch mit der Erzählform erkennbar. Stein wollte Amerika als neue Nation schildern, "whose tradition it had taken scarcely sixty years to create". Im Mittelpunkt sollten drei Generationen zweier Immigrantenfamilien stehen, die Dehnings und die Herslands. "The old people in a new world, the new people made out of old, that is the story that I mean to tell, for that is what really is and what I really know." Obwohl sie den Roman als Gesellschaftspanorama anlegte, konzentrierte sich Stein von Anfang an auf das Privatleben ihrer Protagonisten. Im Gegensatz zu den Realisten des 19. Jahrhunderts, die den Konflikt von Neigung und Pflicht, von sozialen Normen und subjektiver Moral in den Mittelpunkt der Handlung stellten, folgte Stein dem Programm des Naturalismus und richtete ihr Interesse nicht auf die Handlungen und Handlungsspielräume der Subjekte, sondern auf die gesellschaftlichen Kräfte, die Subjektivität formen und prägen. Der Titel 'The Making of Americans' fasst die Ausbildung amerikanischer Identität als einen beinah industriellen Herstellungsprozess sozialer Identität und deutet darin ein erstes Motiv für eine serielle Schreibweise an.
Desert dust is one of the most abundant ice nucleating particle types in the atmosphere. Traditionally, clay minerals were assumed to determine the ice nucleation ability of desert dust and constituted the focus of ice nucleation studies over several decades. Recently some feldspar species were identified to be ice active at much higher temperatures than clay minerals, redirecting studies to investigate the contribution of feldspar to ice nucleation on desert dust. However, so far no study has shown the atmospheric relevance of this mineral phase.
For this study four dust samples were collected after airborne transport in the troposphere from the Sahara to different locations (Crete, the Peloponnese, Canary Islands, and the Sinai Peninsula). Additionally, 11 dust samples were collected from the surface from nine of the biggest deserts worldwide. The samples were used to study the ice nucleation behavior specific to different desert dusts. Furthermore, we investigated how representative surface-collected dust is for the atmosphere by comparing to the ice nucleation activity of the airborne samples. We used the IMCA-ZINC setup to form droplets on single aerosol particles which were subsequently exposed to temperatures between 233 and 250 K. Dust particles were collected in parallel on filters for offline cold-stage ice nucleation experiments at 253–263 K. To help the interpretation of the ice nucleation experiments the mineralogical composition of the dusts was investigated. We find that a higher ice nucleation activity in a given sample at 253 K can be attributed to the K-feldspar content present in this sample, whereas at temperatures between 238 and 245 K it is attributed to the sum of feldspar and quartz content present. A high clay content, in contrast, is associated with lower ice nucleation activity. This confirms the importance of feldspar above 250 K and the role of quartz and feldspars determining the ice nucleation activities at lower temperatures as found by earlier studies for monomineral dusts. The airborne samples show on average a lower ice nucleation activity than the surface-collected ones. Furthermore, we find that under certain conditions milling can lead to a decrease in the ice nucleation ability of polymineral samples due to the different hardness and cleavage of individual mineral phases causing an increase of minerals with low ice nucleation ability in the atmospherically relevant size fraction. Comparison of our data set to an existing desert dust parameterization confirms its applicability for climate models. Our results suggest that for an improved prediction of the ice nucleation ability of desert dust in the atmosphere, the modeling of emission and atmospheric transport of the feldspar and quartz mineral phases would be key, while other minerals are only of minor importance.
Desert dust is one of the most abundant ice nucleating particle types in the atmosphere. Tra ditionally, clay minerals were assumed to determine the ice nucleation ability of desert dust and constituted the focus of ice nucleation studies. Only recently some feldspar species were identified to be ice-active at much higher temperatures than clay minerals, redirecting studies to investigate the contribution of feldspar to ice nucleation on desert dust. However, so far no study has shown the atmospheric relevance of this mineral phase.
For this study four dust samples were collected after airborne transport in the troposphere from the Sahara to different locations (Crete, the Peloponnese, Canary Islands and the Sinai Peninsula). Additionally, eleven dust samples were collected from the surface from nine of the biggest deserts worldwide. The samples were used to study the ice nucleation behavior specific to different desert dusts. Furthermore we investigated how representative ice nucleation on surface-collected dust is for that in the atmosphere by comparing to the ice nucleation activity of the airborne samples. We used the IMCA-ZINC set-up to form droplets on single aerosol particles which were subsequently exposed to temperatures between 233 - 250 K. Dust particles were collected in parallel on filters for offline cold stage ice nucleation experiments at 253 - 263 K. To help the interpretation of the results from the ice nucleation experiments the mineralogical composition of the dusts was investigated.We found that a higher ice nucleation activity in a given sample can be attributed at 253 K to the K-feldspar content present in this sample whereas at temperatures between 238 - 245 K it is attributed to the sum of feldspar and quartz content present. A high clay content on the other hand is associated with a lower ice nucleation activity of a sample. This confirms the importance of feldspar at T > 250 K and the role of quartz and feldspars determining the ice nucleation activities at lower T as found by earlier studies for monomineral dust surrogates. Furthermore, we find that milling may lead to a decrease in the ice nucleation ability of polymineral samples due to a change in mineralogical composition in the atmospherically relevant size fraction arising from the different hardness and cleavage of individual mineral phases. Comparison of our comprehensive data set to an existing desert dust parameterization confirms its applicability for climate models. Our results suggest that for an improved prediction of the ice nucleation ability of desert dust in the atmosphere, the modelling of emission and atmospheric transport of the feldspar and quartz mineral phases would be key while other minerals are only of minor importance.
In situ single particle analysis of ice particle residuals (IPRs) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January–February 2013. During the 4-week campaign more than 70 000 out-of-cloud aerosol particles and 595 IPRs were analyzed covering a particle size diameter range from 100 nm to 3 µm. The IPRs were sampled during 273 h while the station was covered by mixed-phase clouds at ambient temperatures between −27 and −6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. The outcome of these laboratory studies was characteristic marker peaks for each investigated particle type. These marker peaks were applied to the field data. In the sampled IPRs we identified a larger number fraction of primary aerosol particles, like soil dust (13 ± 5 %) and minerals (11 ± 5 %), in comparison to out-of-cloud aerosol particles (2.4 ± 0.4 and 0.4 ± 0.1 %, respectively). Additionally, anthropogenic aerosol particles, such as particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPRs than in the out-of-cloud aerosol. In the out-of-cloud aerosol we identified a large fraction of aged particles (31 ± 5 %), including organic material and secondary inorganics, whereas this particle type was much less abundant (2.7 ± 1.3 %) in the IPRs. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPRs in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPRs.
In-situ single particle analysis of ice particle residuals (IPR) and out-of-cloud aerosol particles was conducted by means of laser ablation mass spectrometry during the intensive INUIT-JFJ/CLACE campaign at the high alpine research station Jungfraujoch (3580 m a.s.l.) in January/February 2013. During the four week campaign more than 70000 out-of-cloud aerosol particles and 595 IPR were analyzed covering a particle size diameter range from 100 nm to 3 μm. The IPR were sampled during 273 hours while the station was covered by mixed-phase clouds at ambient temperatures between -27 °C and -6 °C. The identification of particle types is based on laboratory studies of different types of biological, mineral and anthropogenic aerosol particles. As outcome instrument specific marker peaks for the different investigated particle types were obtained and applied to the field data. The results show that the sampled IPR contain a larger relative amount of natural, primary aerosol, like soil dust (13 %) and minerals (11 %), in comparison to out-of-cloud aerosol particles (2 % and <1 %, respectively). Additionally, anthropogenic aerosol particles, like particles from industrial emissions and lead-containing particles, were found to be more abundant in the IPR than in the out-of-cloud aerosol. The out of-cloud aerosol contained a large fraction of aged particles (30 %, including organic material and secondary inorganics), whereas this particle type was much less abundant (3 %) in the IPR. In a selected subset of the data where a direct comparison between out-of-cloud aerosol particles and IPR in air masses with similar origin was possible, a pronounced enhancement of biological particles was found in the IPR.
Size-resolved long-term measurements of atmospheric aerosol and cloud condensation nuclei (CCN) concentrations and hygroscopicity were conducted at the remote Amazon Tall Tower Observatory (ATTO) in the central Amazon Basin over a 1-year period and full seasonal cycle (March 2014–February 2015). The measurements provide a climatology of CCN properties characteristic of a remote central Amazonian rain forest site.
The CCN measurements were continuously cycled through 10 levels of supersaturation (S = 0.11 to 1.10 %) and span the aerosol particle size range from 20 to 245 nm. The mean critical diameters of CCN activation range from 43 nm at S = 1.10 % to 172 nm at S = 0.11 %. The particle hygroscopicity exhibits a pronounced size dependence with lower values for the Aitken mode (κAit = 0.14 ± 0.03), higher values for the accumulation mode (κAcc = 0.22 ± 0.05), and an overall mean value of κmean = 0.17 ± 0.06, consistent with high fractions of organic aerosol.
The hygroscopicity parameter, κ, exhibits remarkably little temporal variability: no pronounced diurnal cycles, only weak seasonal trends, and few short-term variations during long-range transport events. In contrast, the CCN number concentrations exhibit a pronounced seasonal cycle, tracking the pollution-related seasonality in total aerosol concentration. We find that the variability in the CCN concentrations in the central Amazon is mostly driven by aerosol particle number concentration and size distribution, while variations in aerosol hygroscopicity and chemical composition matter only during a few episodes.
For modeling purposes, we compare different approaches of predicting CCN number concentration and present a novel parametrization, which allows accurate CCN predictions based on a small set of input data.
A handling study to assess use of the Respimat(®) Soft Mist™ inhaler in children under 5 years old
(2015)
Background: Respimat® Soft Mist™ Inhaler (SMI) is a hand-held device that generates an aerosol with a high, fine-particle fraction, enabling efficient lung deposition. The study objective was to assess inhalation success among children using Respimat SMI, and the requirement for assistance by the parent/caregiver and/or a valved holding chamber (VHC).
Methods: This open-label study enrolled patients aged <5 years with respiratory disease and history of coughing and/or recurrent wheezing. Patients inhaled from the Respimat SMI (air only; no aerosol) using a stepwise configuration: “1” (dose released by child); “2” (dose released by parent/caregiver), and “3” (Respimat SMI with VHC, facemask, and parent/caregiver help). Co-primary endpoints included the ability to perform successful inhalation as assessed by the investigators using a standardized handling questionnaire and evaluation of the reasons for success. Inhalation profile in the successful handling configuration was verified with a pneumotachograph. Patient satisfaction and preferences were investigated in a questionnaire.
Results: Of the children aged 4 to <5 years (n=27) and 3 to <4 years (n=30), 55.6% and 30.0%, respectively, achieved success without a VHC or help; with assistance, another 29.6% and 10.0%, respectively, achieved success, and the remaining children were successful with VHC. All children aged 2 to <3 years (n=20) achieved success with the Respimat SMI and VHC. Of those aged <2 years (n=22), 95.5% had successful handling of the Respimat SMI with VHC and parent/caregiver help. Inhalation flow profiles generally confirmed the outcome of the handling assessment by the investigators. Most parent/caregiver and/or child respondents were satisfied with operation, instructions for use, handling, and ease of holding the Respimat SMI with or without a VHC.
Conclusions: The Respimat SMI is suitable for children aged <5 years; however, children aged <5 years are advised to add a VHC to complement its use.
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
Size-resolved long-term measurements of atmospheric aerosol and cloud condensation nuclei (CCN) concentrations as well as hygroscopicity were conducted at the remote Amazon Tall Tower Observatory (ATTO) in the central Amazon Basin over a one-year period and full seasonal cycle (March 2014 - February 2015). The presented measurements provide a climatology of CCN properties for a characteristic central Amazonian rain forest site.
The CCN measurements were continuously cycled through 10 levels of supersaturation (S = 0.11 to 1.10 %) and span the aerosol particle size range from 20 to 245 nm. The observed mean critical diameters of CCN activation range from 43 nm at S = 1.10 % to 172 nm at S = 0.11 %. The particle hygroscopicity exhibits a pronounced size dependence with lower values for the Aitken mode (κAit = 0.14 ± 0.03), elevated values for the accumulation mode (κAcc = 0.22 ± 0.05), and an overall mean value of κmean = 0.17 ± 0.06, consistent with high fractions of organic aerosol.
The hygroscopicity parameter κ exhibits remarkably little temporal variability: no pronounced diurnal cycles, weak seasonal trends, and few short-term variations during long-range transport events. In contrast, the CCN number concentrations exhibit a pronounced seasonal cycle, tracking the pollution-related seasonality in total aerosol concentration. We find that the variability in the CCN concentrations in the central Amazon is mostly driven by aerosol particle number concentration and size distribution, while variations in aerosol hygroscopicity and chemical composition matter only during a few episodes.
For modelling purposes, we compare different approaches of predicting CCN number concentration and present a novel parameterization, which allows accurate CCN predictions based on a small set of input data.
1996 gab es auf dem jährlich in Bologna stattfindenden Festival 'Il Cinema Ritrovato' eine Retrospektive zu Rudolph Valentino. In meinen Aufzeichnungen finde ich den Eindruck von Valentino in 'Camille' notiert. Ich erinnere mich, wie ich hingerissen, ergriffen war von einer Geste des Sich-fallen-Lassens vor der Geliebten, an der Geliebten. Eine Geste, von der ich versuchsweise sagen könnte, dass sich in ihr absolute Verehrung und vollständige physische Hingabe mischen. Doch ist jede Deutung unzureichend, denn die Geste ergreift mich schließlich ganz physisch, wird in der Ergriffenheit unbegreiflich. Ich suchte das damals notierte Phänomen auf einer kümmerlichen DVD-Reproduktion des Films wieder auf. Es ist der Moment, da sich der Held des Films, Armand/Valentino, aus seiner Befangenheit in noch unerwiderter Liebe auf einmal löst - jedoch eben nicht, um zu handeln, vielmehr um sich erschütternd in seiner Ohnmacht zu offenbaren. Wenn er Marguerites/Nazimovas Knie unter dem kostbaren Stoff des Kleides umfasst, den Kopf an diesen Schleier über der Haut lehnt oder schmiegt, dann hat er in der Bewegung zuvor schon auf unerhörte Weise unbedingtes erotisches Verlangen mitgeteilt. Derart ist dieser Körper, diese männliche Person, die wir sehen, dem Begehren ausgeliefert, dass jeder Akt unmöglich wird. Wohin sollte er sich auch richten? Nach außen, auf die Frau, oder auf dies Ungeheure im Innern? Was bleibt, ist das Sich-fallen-Lassen in die Passivität, in ein Niedergleiten an der Oberfläche von Marguerite, das zugleich ein Hineingleiten in das eigene Innerste ist. 'A fallen man' - der Film verweilt bei dem hingegebenen Valentino. Das löst eine Fülle von Assoziationen aus: Ein Geschlechterwechsel scheint auf - nicht die Frau, der Mann gibt sich hin, wird ein Gefallener, prostituiert sich als Schauspieler (etwas, was Fans wie Kritiker an Valentino bemerkt haben) -, ebenso erscheint eine Empathie des Mannes mit der Prostituierten. Im Kino, anders als in Alexandre Dumas' Roman, teilt sich die Anteilnahme nicht durch viele Worte mit, sondern durch Mimesis.
The total stratospheric organic chlorine and bromine burden was derived from balloon-borne measurements in the tropics (Teresina, Brazil, 5°04´ S, 42°52´ W) in 2005. Whole air samples were collected cryogenically at altitudes between 15 and 34 km. For the first time, we report measurements of a set of 28 chlorinated and brominated substances in the tropical upper troposphere and stratosphere including ten substances with an atmospheric lifetime of less than half a year. The substances were quantified using pre-concentration techniques followed by Gas Chromatography with Mass Spectrometric detection. In the tropical tropopause layer at altitudes between 15 and 17 km we found 1.1–1.4% of the chlorine and 6–8% of the bromine to be present in the form of very short-lived organic compounds. By combining the data with tropospheric reference data and age of air observations the abundances of inorganic chlorine and bromine (Cly and Bry) were derived. At an altitude of 34 km we calculated 3062 ppt of Cly and 17.5 ppt of Bry from the decomposition of both long- and short-lived organic source gases. Furthermore we present indications for the presence of additional organic brominated substances in the tropical upper troposphere and stratosphere.
Bild und Leidenschaft
(2010)
This experience, listening to the radio version of "The Green Hills of Earth" was the first form in which I encountered a problem that in the following years continued to haunt much of the work I have done ever since. This problem has a double aspect, since it involves both 'the visibility of the invisible' and, inseparably linked to it, that of the 'invisibility of the visible'. Far from excluding each other, as opposites are commonly expected to do, 'visibility' and 'invisibility' seem here to be inextricably linked, although not simply the same. The prominence, in the story, of repetition and recurrence, indeed of doubling, suggests that another term should be introduced to describe this curious relationship of non-exclusive opposition, that of 'divisibility'. Visibility divides itself into what is visible and what is invisible. And given the fact that this is also a question of life and death, of living and dying, the process of divisibility can be said to produce not just appearances, but 'apparitions' (which in English, unlike its 'false friend' in French, signifies 'ghosts' and not just appearances). Listening to the radio in that darkened bedroom, I think what I experienced was something like the apparition of such divisibility, by which the invisible seemed to become visible, but only by making the visible invisible. Much later I learned that this was a phenomenon - if one can call it that - quite familiar to philosophers and aestheticians who generally tried to interpret it with the use of words such as "fantasy" and "imagination": what Kant, for example, in 'Kritik der reinen Vernunft' calls "productive" as distinct from "reproductive imagination", which does not merely reproduce what one sees but which produces representations of things that were never seen (and perhaps could never be seen). But I never felt that such concepts were capable of accounting for the strange capacity of those invisible 'images' to produce feelings whose intensity seemed in direct proportion to their indistinct and relatively indeterminate - non-objective - quality.
Um die Funktionsweise von biologischen Prozessen zu untersuchen, werden Trigger-Signale benötigt, die die Prozesse initiieren können, ohne dabei dem Organismus zu schaden oder Nebenreaktionen hervorzurufen. Ein geeignetes Trigger-Signal stellt Licht dar, da es bei geeigneter Wellenlänge nichtinvasiv ist und nur wenige biologische Prozesse durch Licht gesteuert werden. Um einen Prozess mit Licht aktivierbar zu machen, benötigt man eine lichtsensitive Einheit, beispielsweise eine photolabile Schutzgruppe, die durch die Bestrahlung mit Licht einen zuvor blockierten Bereich freisetzt.
Hauptziel dieser Arbeit war es die Zweiphotonen-Technik für die Photolyse von photolabil geschützten Oligonukleotiden nutzbar zu machen und das Photolyseergebnis zu visualisieren.
Dazu wurden zunächst verschiedene mit Zweiphotonen-sensitiven Schutzgruppen modifizierte Phosphoramidite synthetisiert und über Festphasensynthese in Oligonukleotide eingebaut. Die Oligonukleotide mit den erstmals neu eingebauten Schutzgruppen ANBP und hNDBF wurden zunächst auf ihre Einphotonen-Eigenschaften, wie Schmelzpunkt, Absorptionsverhalten und Quantenausbeute untersucht. Weiterhin wurden erste Versuche zur wellenlängenselektiven Photolyse von hNDBF- und ANBP-geschützten Oligonukleotiden durchgeführt.
Die Existenz eines Zweiphotonen-induzierten Effekts kann durch die quadratische Abhängigkeit des erzeugten Effekts von der eingestrahlten Leistung nachgewiesen werden. Dazu wurde ein Verdrängungs-Assay entwickelt, dessen Doppelstrang-Sonde aus einem FRET-Paar besteht. Der Fluorophor-markierte Strang dient dabei als Gegenstrang zum photolabil geschützten Strang. Durch einen Thiol-Linker am photolabil geschützten Oligonukleotid konnte dieses erfolgreich in Maleimid-Hydrogele immobilisiert werden und der Verdrängungs-Assay im Gel durchgeführt werden. Die immobilisierten Stränge enthielten DEACM bzw. ANBP Schutzgruppen. Neben der quadratischen Abhängigkeit der Photolyse von der eingestrahlten Leistung konnten in diesen Hydrogelen auch 3D-aufgelöste Photolysen realisiert werden, die eindeutig die Zwei-Photonen-Photolyse belegen. Diese 3D-Experimente wurden zusammen mit Dr. Stephan Junek am MPI für Hirnforschung durchgeführt. Durch die Wahl zweier unterschiedlicher Sequenzen für die dTDEACM und dGANBP modifizierten Stränge und zwei unterschiedlicher Fluorophore für die Doppelstrang-Sonden, konnte die orthogonale Zweiphotonen-Photolyse gezeigt werden. Um zu zeigen, dass die Zweiphotonen-Photolyse von Oligonukleotiden auch in Organismen realisiert werden kann ohne das biologische System zu schädigen, wurde versucht den Verdrängungs-Assay auch in Zellen durchzuführen. Durch die Verwendung der Patch-Clamp-Technik in Zusammenarbeit mit Dr. Stephan Junek am MPI für Hirnforschung konnten die Stränge über die Elektrolyt-Lösung in Hippocampus-Neuronen eingebracht werden und durch Zweiphotonen-Bestrahlung dort photolysiert werden, was zu einem deutlichen Fluoreszenzanstieg führte. Durch die angeschlossene Patch-Clamp-Pipette konnten so zusätzlich elektrophysiologische Messungen durchgeführt werden, die zeigten, dass die durchgeführte Zweiphotonen-Bestrahlung nicht invasiv für die Zellen ist.
Die durchgeführten Experimente beweisen, dass Zweiphotonen-sensitive Schutzgruppen auf Oligonukleotiden photolysiert werden können und dass ihr Einsatz auch in biologischen Systemen möglich ist. Der entwickelte Verdrängungs-Assay ermöglicht es weiterhin neue photolabile Schutzgruppen auf Oligonukleotiden auf ihre Zweiphotonen-Sensitivität zu untersuchen.
Ein weiteres Projekt beschäftigte sich mit der Synthese der neuen Schutzgruppe DMA-NDBF-OH, die in-silico von der Arbeitsgruppe von Prof. Andreas Dreuw aus Heidelberg als effiziente Zweiphotonen-sensitive Schutzgruppe beschrieben wird. Es wurde versucht DMA-NDBF-OH über zwei Syntheserouten herzustellen. Eine Route basierte auf der Einführung der Funktionalitäten an einem unmodifizierten Dibenzofuran, die leider an der Bromierung der Seitenkette scheiterte. Die zweite Syntheseroute wurde in Anlehnung an die NDBF-Synthese von Deiters et al., bei der das Dibenzofuran durch eine Kondensation zweier modifizierter Benzolringe und einem Pd-katalysierten Ringschluss aufgebaut wird, durchgeführt. Mit dieser Syntheseroute konnte das DMA-NDBF-OH erfolgreich synthetisiert werden. Aufgrund ihrer starken bathochromen Verschiebung sollte sich diese Schutzgruppe hervorragend für die wellenlängenselektive Photolyse auf Ein- und Zweiphotonenebene eignen.
Unmittelbar auf das fast friedensselig gestimmte Sterbegedicht der "Kleinen Passion" folgt ein seltsam derbkomisches, balladesk trotziges Klagelied einer Kröte, welche partout nicht sterben kann, ein offenkundiger Kontrapunkt oder satirischer Πάρωδος zum elegischen Passionsspiel über den Mückentod. Die beiden Gedichte stehen in Gottfried Kellers 'Gesammelten Gedichten' von 1888 in der zweitletzten Abteilung unter "Vermischte Gedichte" einander zugeordnet. Wie der Titel andeutet, findet sich hier ein recht buntes Allerlei von Texten unterschiedlichster Art und verschiedenster Entstehungszeit - die "Krötensage" wurde zwanzig Jahre vor "Kleine Passion" erstmals publiziert, nämlich 1852. Gleichwohl ist die gruppierende Hand Kellers unübersehbar, und dieser Ordnungswille wurde in der Keller-Forschung etwa von Emil Ermatinger oder Jonas Fränkel denn auch früh festgehalten. Konkret zu den beiden Gedichten sagt letzterer indessen lediglich: "Das Schicksal der Kreatur wird in zwei gegensätzlichen Gedichten abgewandelt." Der Bezüge sind freilich weit vielfältigere: Neben den jahreszeitlichen Kontrastparallelen - die "Kleine Passion" spielt im herbstlichen September, die "Krötensage" im Maienfrühling - und dem bedeutungsgeladenen Verhältnis von Leben, Körper und Hülle, dem "Futterale" - in der "Krötensage" der Stein, in der "Kleinen Passion" das dichterliche Buch - ist den beiden auch dasselbe Thema eingeschrieben: Letztlich geht es um die altehrwürdige 'ars moriendi' in ihrer dialektischen Verflochtenheit mit der 'ars vivendi'. Auch der satirische Grundklang erweist sich bei genauerem Hinschauen als gemeinsam.
Bill Violas mediale Neubearbeitungen der Passion Christi mögen hier als ein produktiver Umweg fungieren, der die Abkehr von einer Ikonographie der Passion ermöglicht und eine neue Sicht auf die Passion als Denkstil eröffnet. Denn durch einen solchen leidenschaftlichen Denkstil, gemäß der Bedeutung von 'Passion' als intensiver Hingabe an eine Person oder ein Objekt, zeichnet sich Sigrid Weigels wissenschaftliche Praxis aus, so etwa durch die Leidenschaft für dialektische Analyseverfahren von Bild und Schrift, verstanden als kritische Praxis. Solch ein Erkenntnisinteresse versucht unermüdlich, eine Neubestimmung kritischer Wissenschaft vorzunehmen, die sich sowohl im historischen Prozess bewährt als auch in gegenwärtigen Belangen verankert bleibt. Es folgt eine kritische Lektüre von Bildern, die jeweils in dichten Beschreibungen eingeführt werden. Drei Beispiele aus der Gegenwartskunst veranschaulichen die Konstituierung von Identitäten mit Blick auf die Diskurse von Geschlecht, Rasse und sexueller Orientierung und damit die Konstruktion einer Identität im Spannungsfeld von Subjektivität und Fremdbestimmung. Die Bilder verdeutlichen dabei die resultierenden Konflikte zwischen eigenem Erleben und vorherrschenden Strukturen.
Die telefonische Revolution des Bildes : Effekte einer Kommunikationsobsession des 21. Jahrhunderts
(2010)
Um was für ein Objekt handelt es sich eigentlich beim gegenwärtigen Mobiltelefon? Im Folgenden sollen kurz drei Elemente skizziert werden, die für die historische Entwicklung und das gegenwärtige Design des Mobiltelefons von zentraler Bedeutung sind: Das Mobiltelefon ist (1) ein höchst hybrides Medium, das eine ganze Reihe von Medientechniken verbindet und dabei auch diese eigentümliche Verbindung von Telefon und digitalem Bild herstellt; es ist (2) eine mobile Operationseinheit, die sich von einem physischen oder architektonischen Ort löst und dessen Mobilisierung (3) die Minimierung der Interfaces forciert. All dies erzeugt die neuen Bedingungen für eine Revolution des digitalen Bildes im Zeichen des Telefons.
Kinoleidenschaft, geteilt
(2010)
Im Kino geht es um Sehnsüchte und Leidenschaften - das ist ein Allgemeinplatz. Weitaus seltener bemerkt worden ist, dass es einem echten Vertrauensbeweis gleichkommt, gemeinsam ins Kino zu gehen. Der Kinogänger offenbart dabei die eigenen Passionen - allein schon durch den Vorschlag, diesen oder jenen Film anzuschauen. Und er lässt die anderen an recht persönlichen Erschütterungen teilhaben: dem Erschrecken, Seufzen, Kichern oder auch Schluchzen. Gemildert wird diese Offenherzigkeit jedoch dadurch, dass auch die Begleiter im Halbdunkel aus dem Seitenwinkel wahrnehmbar sind. Nicht selten gleichen sich auf diese Weise die Reaktionen miteinander ab. Ein ostentatives Aufstöhnen wird durch ein beherrschtes Nicht-Reagieren beantwortet, ein lautes Lachen durch erleichtertes Mitlachen. Die Kino-Gemeinschaft ist durch ein System kommunizierender Blickwechsel miteinander verbunden.
Drei Figuren
(2010)
BACKGROUND: Despite its impact on female health worldwide, no efforts have been made to depict the global architecture of ovarian cancer research and to understand the trends in the related literature. Hence, it was the objective of this study to assess the global scientific performance chronologically, geographically and in regards to economic benchmarks using bibliometric tools and density equalizing map projections.
METHODS: The NewQIS platform was employed to identify all ovarian cancer related articles published in the Web of Science since 1900. The items were analyzed regarding quantitative aspects (e.g. publication date, country of origin) and parameters describing the recognition of the work by the scientific community (e.g. citation rates).
RESULTS: 23,378 articles on ovarian cancer were analyzed. The USA had the highest activity of ovarian cancer research with a total of n = 9312 ovarian cancer-specific publications, followed by the UK (n = 1900), China (n = 1813), Germany (n = 1717) and Japan (n = 1673). Ovarian cancer-specific country h-index also showed a leading position of the USA with an h-index (HI) of 207, followed by the UK (HI = 122), Canada (HI = 99), Italy (HI = 97), Germany (HI = 84), and Japan (HI = 81). In the socio-economic analysis, the USA were ranked first with an average of 175.6 ovarian cancer-related publications per GDP per capita in 1000 US-$, followed by Italy with an index level of 46.85, the UK with 45.48, and Japan with 43.3. Overall, the USA and Western European nations, China and Japan constituted the scientific power players publishing the majority of highly cited ovarian cancer-related articles and dominated international collaborative efforts. African, Asian and South American countries played almost no visible role in the scientific community.
CONCLUSIONS: The quantity and scientific recognition of publications related to ovarian cancer are continuously increasing. The research endeavors in the field are concentrated in high-income countries with no involvement of lower-resource nations. Hence, worldwide collaborative efforts with the aim to exchange epidemiologic data, resources and knowledge have to be strengthened in the future to successfully alleviate the global burden related to ovarian cancer.
Autophagy can act either as a tumor suppressor or as a survival mechanism for established tumors. To understand how autophagy plays this dual role in cancer, in vivo models are required. By using a highly heterogeneous C. elegans germline tumor, we show that autophagy-related proteins are expressed in a specific subset of tumor cells, neurons. Inhibition of autophagy impairs neuronal differentiation and increases tumor cell number, resulting in a shorter life span of animals with tumors, while induction of autophagy extends their life span by impairing tumor proliferation. Fasting of animals with fully developed tumors leads to a doubling of their life span, which depends on modular changes in transcription including switches in transcription factor networks and mitochondrial metabolism. Hence, our results suggest that metabolic restructuring, cell-type specific regulation of autophagy and neuronal differentiation constitute central pathways preventing growth of heterogeneous tumors.
Based on a non-rigorous formalism called the “cavity method”, physicists have made intriguing predictions on phase transitions in discrete structures. One of the most remarkable ones is that in problems such as random k-SAT or random graph k-coloring, very shortly before the threshold for the existence of solutions there occurs another phase transition called condensation [Krzakala et al., PNAS 2007]. The existence of this phase transition seems to be intimately related to the difficulty of proving precise results on, e. g., the k-colorability threshold as well as to the performance of message passing algorithms. In random graph k-coloring, there is a precise conjecture as to the location of the condensation phase transition in terms of a distributional fixed point problem. In this paper we prove this conjecture, provided that k exceeds a certain constant k0.
Lactate is an essential component of carbon metabolism in mammals. Recently, lactate was shown to signal through the G protein coupled receptor 81 (GPR81) and to thus modulate inflammatory processes. This study demonstrates that lactate inhibits pro-inflammatory signaling in a GPR81-independent fashion. While lipopolysaccharide (LPS) triggered expression of IL-6 and IL-12 p40, and CD40 in bone marrow-derived macrophages, lactate was able to abrogate these responses in a dose dependent manner in Gpr81-/- cells as well as in wild type cells. Macrophage activation was impaired when glycolysis was blocked by chemical inhibitors. Remarkably, lactate was found to inhibit LPS-induced glycolysis in wild type as well as in Gpr81-/- cells. In conclusion, our study suggests that lactate can induce GPR81-independent metabolic changes that modulate macrophage pro-inflammatory activation.
Reconstructions of the vegetation of Europe during the Last Glacial Maximum (LGM) are an enigma. Pollen-based analyses have suggested that Europe was largely covered by steppe and tundra, and forests persisted only in small refugia. Climate-vegetation model simulations on the other hand have consistently suggested that broad areas of Europe would have been suitable for forest, even in the depths of the last glaciation. Here we reconcile models with data by demonstrating that the highly mobile groups of hunter-gatherers that inhabited Europe at the LGM could have substantially reduced forest cover through the ignition of wildfires. Similar to hunter-gatherers of the more recent past, Upper Paleolithic humans were masters of the use of fire, and preferred inhabiting semi-open landscapes to facilitate foraging, hunting and travel. Incorporating human agency into a dynamic vegetation-fire model and simulating forest cover shows that even small increases in wildfire frequency over natural background levels resulted in large changes in the forested area of Europe, in part because trees were already stressed by low atmospheric CO2 concentrations and the cold, dry, and highly variable climate. Our results suggest that the impact of humans on the glacial landscape of Europe may be one of the earliest large-scale anthropogenic modifications of the earth system.
Single long-chain omega-3 fatty acids (e.g. docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA)) are known for their neuroprotective properties associated with ischemic stroke. This pilot study aimed to test the effectiveness of an acute treatment with a long-chain omega-3 lipid emulsion (Omegaven 10%®, OGV) that contains fish oil (DHA 18 mg/ml; EPA 21 mg/ml) and α-tocopherol (0.2 mg/ml) in a transient middle cerebral artery occlusion (MCAO) model of ischemic stroke in mice. For this purpose, female CD-1 mice were anesthetized and subjected to 90 minutes of MCAO. To reflect a clinically relevant situation for an acute treatment, either after induction of stroke or after reperfusion, a single dose of OGV was injected intravenously into the tail vein (5 ml/kg b.w.). A neurological severity score was used to assess motor function and neurological outcome. Stroke-related parameters were determined 24 hours after MCAO. Microdialysis was used to collect samples from extracellular space of the striatum. Mitochondrial function was determined in isolated mitochondria or dissociated brain cells. Inflammation markers were measured in brain homogenate. According to control experiments, neuroprotective effects could be attributed to the long-chain omega-3 content of the emulsion. Intravenous injection of OGV reduced size and severity of stroke, restored mitochondrial function, and prevented excitotoxic glutamate release. Increases of pro-inflammatory markers (COX-2 and IL-6) were attenuated. Neurological severity scoring and neurochemical data demonstrated that acute OGV treatment shortly after induction of stroke was most efficient and able to improve short-term neurological outcome, reflecting the importance of an acute treatment to improve the outcome. Summarising, acute treatment of stroke with a single intravenous dose of OGV provided strong neuroprotective effects and was most effective when given immediately after onset of ischemia. As OGV is an approved fishoil emulsion for parenteral nutrition in humans, our results may provide first translational data for a possible early management of ischemic stroke with administration of OGV to prevent further brain damage.
Preserving a patient’s own teeth—even in a difficult situation—is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20–23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-β1 (TGF-β1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-β1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-β1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.
It is long known that Kasugamycin inhibits translation of canonical transcripts containing a 5’-UTR with a Shine Dalgarno (SD) motif, but not that of leaderless transcripts. To gain a global overview of the influence of Kasugamycin on translation efficiencies, the changes of the translatome of Escherichia coli induced by a 10 minutes Kasugamycin treatment were quantified. The effect of Kasugamycin differed widely, 102 transcripts were at least twofold more sensitive to Kasugamycin than average, and 137 transcripts were at least twofold more resistant, and there was a more than 100-fold difference between the most resistant and the most sensitive transcript. The 5’-ends of 19 transcripts were determined from treated and untreated cultures, but Kasugamycin resistance did neither correlate with the presence or absence of a SD motif, nor with differences in 5’-UTR lengths or GC content. RNA Structure Logos were generated for the 102 Kasugamycin-sensitive and for the 137 resistant transcripts. For both groups a short Shine Dalgarno (SD) motif was retrieved, but no specific motifs associated with resistance or sensitivity could be found. Notably, this was also true for the region -3 to -1 upstream of the start codon and the presence of an extended SD motif, which had been proposed to result in Kasugamycin resistance. Comparison of the translatome results with the database RegulonDB showed that the transcript with the highest resistance was leaderless, but no further leaderless transcripts were among the resistant transcripts. Unexpectedly, it was found that translational coupling might be a novel feature that is associated with Kasugamycin resistance. Taken together, Kasugamycin has a profound effect on translational efficiencies of E. coli transcripts, but the mechanism of action is different than previously described.
The condensation phase transition and the number of solutions in random graph and hypergraph models
(2016)
This PhD thesis deals with two different types of questions on random graph and random hypergraph structures.
One part is about the proof of the existence and the determination of the location of the condensation phase transition. This transition will be investigated for large values of $k$ in the problem of $k$-colouring random graphs and in the problem of 2-colouring random $k$-uniform hypergraphs, where in the latter case we investigate a more general model with finite inverse temperature.
The other part deals with establishing the limiting distribution of the number of solutions in these structures in density regimes below the condensation threshold.
The three 'Materialienbände' - 'Schnitte'; 'Rom, Blicke'; and 'Erkundungen für die Präzisierung des Gefühls für einen Aufstand' - that Rolf Dieter Brinkmann produced in the early 1970s have, in the last decade, gradually come to be recognized as central statements of a radically new cultural formation. A peculiar feature of this recognition, though, is the relative puzzlement that lingers over the question as to the 'form' of these volumes. That the three objects resist generic classification is by now a truism of the Brinkmann literature; yet even the construction of a cultural field within which the volumes might be compared to other works has remained elusive. The essay that follows, based largely on a reading of 'Rom, Blicke', is an attempt to construct precisely that cultural field.
Wie kann man Gedichte verstehen, in denen die Rolle von Lesern nicht vorgesehen ist? Was erlebt man mit derartig abweisenden Texten, und wie findet man sich hinein - zumindest ein Stück weit? Von der großen amerikanischen Lyrikerin Emily Dickinson (1830-1886) sind zu ihren Lebzeiten nur zehn Gedichte gedruckt worden, noch dazu anonym und ohne ihre Zustimmung. Dabei hätte die Autorin durchaus Publikationsmöglichkeiten gehabt. Aber sie wollte die formalen und inhaltlichen Anpassungen an den Publikumsgeschmack, die ihr Mentor, der Essayist Thomas Higginson, empfohlen hatte, nicht vornehmen. Grundsätzlich wollte sie sich nicht auf den Marktplatz des Literaturbetriebs zerren lassen. In ihrer Schlafzimmerkommode hinterließ sie bei ihrem Tod ca. 1.800 Gedichte. Ein Drittel davon hatte sie zu Lebzeiten an Freunde und Bekannte weitergeschickt, aus denen sie sich selbst das Lesepublikum für ihre Lyrik schuf. Aber zwei Drittel ihrer Gedichte hatte sie an niemanden verschickt, niemandem gezeigt und vermutlich einzig für sich selbst geschrieben. Kein Wunder, dass diese Gedichte dunkel sind. Wenn die Dichterin selbst die einzige Leserin ihres Textes ist, braucht sie nichts zu erklären. Deshalb, und nicht weil die Gedichte - wie schon behauptet wurde - "von einer sehr fernen Glossolalie gestreift" sind, wirken viele ihrer Texte so rätselhaft.
Passionen der Ordnung
(2010)
In ihrer Schrift 'Über Revolution' (1963) bekennt sich Hannah Arendt zu einer politischen Passion des Mitfühlens - einer 'passion for compassion'. Die Wurzeln dieses Mitfühlens sind wesentlich dem semantischen wie begrifflichen Humus der schottischen Aufklärung entliehen. Der Text ergänzt jene von Arendt idealisierte Figur der griechischen 'polis' als Fundament einer guten, erstrebenswerten Ordnung. Die Resultante aus der Passion des Mitfühlens und der Figur der 'polis' - so will es scheinen - ist die Republik, wie sie sich idealerweise in den Institutionen der Amerikanischen Revolution niederschlägt; und dies in Kontrast zu der von Arendt wenig gelittenen Traditionslinie der Französischen Revolution, die ihrerseits von glühenden, indes wenig regulierten Passionen eines sich sozial begründenden Mitgefühls angefacht wird.
War die "Vernichtung der Sinnlichkeit" durch die "Civilisation" genannte dritte Stufe (nach "Wildheit" und "Barbarei") in der Kulturgeschichte der Menschheit der eine Impuls von Fouriers Sozialutopie, so stellte die Trennung von Körper und Geist, von 'sciences incertaines' und 'sciences fixes' den anderen, mathematisch und musikalisch imprägnierten Impuls dar. Demgegenüber bilden sowohl eine Theorie der Leidenschaften, der 'association passionnelle', als auch eine pädagogische Haus- und Lebensordnung für die Phalanstères - die idealen Wohn- und Produktionsgenossenschaften - in Fouriers Utopie die 'pivots', so der von ihm erfundene Begriff, das heißt die Grundpfeiler und Leitlinien.
Schon seit Ende der 1980er Jahre und bis heute setzt der Schweizer Künstler Thomas Hirschhorn Gesten in den öffentlichen Raum, aber auch in Museen und in Galerien, die das Wesen eines irrlichternden Mementos aufweisen, Zeichen einer kalkuliert in Szene gesetzten Hilflosigkeit. Dabei erfindet er sozusagen eine Kunstfigur, die seine Werke zu machen scheint. Seine wuchernden Objekte, Schrift- und Bildtafeln, entsprechen Handlungen, die ein Getriebener, ein Wahnsinniger gemacht haben könnte. Hirschhorn betätigt sich somit als Überbringer einer entfesselt leidenschaftlichen Emotionalität, die in krassem Kontrast steht zum kontrollierten, von der Vernunft gelenkten, von übertriebenen Affekten und Irrationalität geläuterten Idealbild des westlich aufgeklärten Kulturmenschen.
Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express β-galactosidase (β-gal) under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3) and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells) showed strong β-gal labeling. In the inner nuclear layer (INL), a minority of glycineric and GABAergic amacrine cells showed β-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, β-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic ‘starburst’ amacrines. At postnatal day 10, there also was a high density of strongly β-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no β-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of β-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.
Combined diabetes-obesity syndromes severely impair regeneration of acute skin wounds in mouse models. This study assessed the contribution of subcutaneous adipose tissue to exacerbated wound inflammatory conditions. Genetically obese (ob/ob) mice showed an increased expression of positive transcriptional effectors of adipocyte differentiation such as Krüppel-like factor (KLF)-5 and peroxisome proliferator-activated receptor (PPAR)-γ and an associated expression of leptin and fatty acid-binding protein (FABP)-4, but also CXCL2 in isolated subcutaneous fat. This observation in obese mice is in keeping with differentially elevated levels of KLF-5, PPAR-γ, leptin, FABP-4 and CXCL2 in in vitro-differentiated 3T3-L1 adipocytes. Notably, CXCL2 expression restrictively appeared upon cytokine (IL-1β/TNF-α) stimulation only in mature, but not immature 3T3-L1 adipocytes. Of importance, the critical regulator of adipocyte maturation, PPAR-γ, was merely expressed in the final phase of in-vitro induced adipocyte differentiation from 3T3-L1 pre-adipocytes. Consistently, the PPAR-γ agonist rosiglitazone suppressed cytokine-induced CXCL2 release from mature adipocytes, but not from early 3T3-L1 adipocyte stages. The inhibitory effect of PPAR-γ activation on CXCL2 release appeared to be a general anti-inflammatory effect in mature adipocytes, as cytokine-induced cyclooxygenase (Cox)-2 was simultaneously repressed by rosiglitazone. In accordance with these findings, oral administration of rosiglitazone to wounded obese mice significantly changed subcutaneous adipocyte morphology, reduced wound CXCL2 and Cox-2 expression and improved tissue regeneration. Thus, our data suggest that PPAR-γ might provide a target to suppress inflammatory signals from mature adipocytes, which add to the prolonged wound inflammation observed in diabetes-obesity conditions.
A variety of joint action studies show that people tend to fall into synchronous behavior with others participating in the same task, and that such synchronization is beneficial, leading to greater rapport, satisfaction, and performance. It has been noted that many of these task environments require simple interactions that involve little planning of action coordination toward a shared goal. The present study utilized a complex joint construction task in which dyads were instructed to build model cars while their hand movements and heart rates were measured. Participants built these models under varying conditions, delimiting how freely they could divide labor during a build session. While hand movement synchrony was sensitive to the different tasks and outcomes, the heart rate measure did not show any effects of interpersonal synchrony. Results for hand movements show that the more participants were constrained by a particular building strategy, the greater their behavioral synchrony. Within the different conditions, the degree of synchrony was predictive of subjective satisfaction and objective product outcomes. However, in contrast to many previous findings, synchrony was negatively associated with superior products, and, depending on the constraints on the interaction, positively or negatively correlated with higher subjective satisfaction. These results show that the task context critically shapes the role of synchronization during joint action, and that in more complex tasks, not synchronization of behavior, but rather complementary types of behavior may be associated with superior task outcomes.
Background: Antiangiogenic treatment of glioblastomas with Bevacizumab lacks predictive markers. Myoinositol (MI) is an organic osmolyte, with intracellular concentration changes depending on the extracellular osmolality. Since Bevacizumab markedly reduces tumor edema and influences the tumor microenvironment, we investigated whether the MI concentration in the tumor changes during therapy.
Methods: We used 1H-magnetic resonance spectroscopy to measure the MI concentrations in the tumor and contralateral control tissue of 39 prospectively recruited patients with recurrent glioblastomas before and 8–12 weeks after starting therapy. 30 patients received Bevacizumab and 9 patients were treated with CCNU/VM26 as control. We performed a survival analysis to evaluate MI as a predictive biomarker for Bevacizumab therapy.
Results: MI concentrations increased significantly during Bevacizumab therapy in tumor (p < .001) and control tissue (p = .001), but not during CCNU/VM26 treatment. For the Bevacizumab cohort, higher MI concentrations in the control tissue at baseline (p = .021) and higher differences between control and tumor tissue (delta MI, p = .011) were associated with longer survival. A Kaplan-Meier analysis showed a median OS of 164 days for patients with a deltaMI < 1,817 mmol/l and 275 days for patients with a deltaMI > 1,817 mmol/l. No differences were observed for the relative changes or the post treatment concentrations. Additionally calculated creatine concentrations showed no differences in between subgroups or between pre and post treatment measurements.
Conclusion: Our data suggest that recurrent glioblastoma shows a strong metabolic reaction to Bevacizumab. Further, our results support the hypothesis that MI might be a marker for early tumor cell invasion. Pre-therapeutic MI concentrations are predictive of overall survival in patients with recurrent glioblastoma treated with Bevacizumab.
Ribosomes are large ribonucleoprotein complexes that are fundamental for protein synthesis. Ribosomes are ribozymes because their catalytic functions such as peptidyl transferase and peptidyl-tRNA hydrolysis depend on the rRNA. rRNA is a heterogeneous biopolymer comprising of at least 112 chemically modified residues that are believed to expand its topological potential. In the present study, we established a comprehensive modification profile of Saccharomyces cerevisiae’s 18S and 25S rRNA using a high resolution Reversed-Phase High Performance Liquid Chromatography (RP-HPLC). A combination of mung bean nuclease assay, rDNA point mutants and snoRNA deletions allowed us to systematically map all ribose and base modifications on both rRNAs to a single nucleotide resolution. We also calculated approximate molar levels for each modification using their UV (254nm) molar response factors, showing sub-stoichiometric amount of modifications at certain residues. The chemical nature, their precise location and identification of partial modification will facilitate understanding the precise role of these chemical modifications, and provide further evidence for ribosome heterogeneity in eukaryotes.
Pulmonary hypertension (PH) is characterized by the increase of the mean pulmonary arterial pressure in the lung circulation. Despite the large number of experimental and clinical studies conducted on pulmonary hypertension, there is no comprehensive work that analyzed the global research activity on PH so far. We retrieved the bibliometric data of the publications on pulmonary hypertension for two periods from the Web of science database. Here, we set the first investigation period from 1900 to 2007 (t1) due to the cited half life of articles and the relating difficulties to interpret the citation parameters. The second evaluation period (t2) covers the time interval from 2008 onwards including the year 2015. The data were analyzed and processed to density-equalizing maps using the NewQIS platform. A total number of 18,986 publications were identified in t1 that come from 85 countries. The US published the highest number of publications (n = 7,290), followed by the UK, Germany, Japan and France. In t2 19,676 items could be found worked out by 130 countries. The raking started just the same with the USA as most publishing nation with 7,127 publications on PH, followed by the UK and Germany. Japan fell back on 6th place, whereas China came into view on the 5th position. Analyzing the average citation rate as a parameter for research quality, Mexico reached the highest value in t1 and Ireland in t2. While, the country specific h-index underlined the leading position of the US research in both evaluation periods again. The average number of international collaboration items was expanding from none in 1978 to 530 items in 2015 with the USA as the country with the highest number of collaboration articles. The present study is the first large scale density-equalizing mapping and scientometric analysis of global PH research activity. Our data draw a sketch of the global research architecture in this field, indicating a need for specific research programs in countries with a lower human development index.
Differentiated neurons can be rapidly acquired, within days, by inducing stem cells to express neurogenic transcription factors. We developed a protocol to maintain long-term cultures of human neurons, called iNGNs, which are obtained by inducing Neurogenin-1 and Neurogenin-2 expression in induced pluripotent stem cells. We followed the functional development of iNGNs over months and they showed many hallmark properties for neuronal maturation, including robust electrical and synaptic activity. Using iNGNs expressing a variant of channelrhodopsin-2, called CatCh, we could control iNGN activity with blue light stimulation. In combination with optogenetic tools, iNGNs offer opportunities for studies that require precise spatial and temporal resolution. iNGNs developed spontaneous network activity, and these networks had excitatory glutamatergic synapses, which we characterized with single-cell synaptic recordings. AMPA glutamatergic receptor activity was especially dominant in postsynaptic recordings, whereas NMDA glutamatergic receptor activity was absent from postsynaptic recordings but present in extrasynaptic recordings. Our results on long-term cultures of iNGNs could help in future studies elucidating mechanisms of human synaptogenesis and neurotransmission, along with the ability to scale-up the size of the cultures.
Background: HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12.
Methods: This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18–70 years with METAVIR F0–F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24.
Results: Of 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3–4 adverse events was lower in the 12-week group than in the 24-week group.
Conclusions: Our findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study.
This study evaluated the interferon-free, oral combination of deleobuvir (non-nucleoside HCV NS5-RNA-polymerase inhibitor) and faldaprevir (HCV NS3/4A-protease inhibitor) with ribavirin in patients with HCV genotype-1b and moderate (Child-Pugh B [CPB], n = 17) or mild hepatic impairment (Child-Pugh A [CPA], n = 18). Patients received faldaprevir 120 mg and deleobuvir (600 mg [CPA], 400 mg [CPB]) twice-daily with weight-based ribavirin for 24 weeks. Baseline characteristics were similar between groups. Among CPA patients, 13/18 completed treatment; discontinuations were for adverse events (AEs, n = 1), lack of efficacy (n = 3) and withdrawal (n = 1). Among CPB patients, 8/17 completed treatment; discontinuations were for AEs (n = 6), withdrawal (n = 1) and ‘other’ (n = 2). Sustained virologic response at post-treatment Week 12 (SVR12) was achieved by 11 (61%) CPA patients (95% confidence interval: 38.6%–83.6%) and 9 (53%) CPB patients (95% confidence interval: 29.2%–76.7%), including most CPA (11/16) patients with Week 4 HCV RNA <25 IU.mL-1 (target detected or not detected) and most CPB (8/9) patients with Week 4 HCV RNA <25 IU.mL-1 (target not detected); 0/4 CPB patients with Week 4 HCV RNA <25 IU.mL-1 (target detected) achieved SVR12. The most common AEs in both groups were nausea, diarrhoea and vomiting. Serious AEs were observed in 9 (53%) CPB patients and 1 (6%) CPA patient. Plasma trough concentrations of deleobuvir and faldaprevir were not substantially different between the CPA and CPB groups. In conclusion, in this small study the safety and efficacy profiles for 24 weeks of treatment with faldaprevir+deleobuvir+ribavirin in patients with mild or moderate hepatic impairment were consistent with the safety and efficacy profile of this regimen in non-cirrhotic patients. Faldaprevir+deleobuvir+ribavirin resulted in SVR12 in 53–61% of patients: proportions achieving SVR4 but not SVR12 were higher than in non-cirrhotic patients and overall response rates were lower than rates reported with other all-oral regimens in patients with cirrhosis.
BACKGROUND: Evaluation of latest generation automated attenuation-based tube potential selection (ATPS) impact on image quality and radiation dose in contrast-enhanced chest-abdomen-pelvis computed tomography examinations for gynaecologic cancer staging.
METHODS: This IRB approved single-centre, observer-blinded retrospective study with a waiver for informed consent included a total of 100 patients with contrast-enhanced chest-abdomen-pelvis CT for gynaecologic cancer staging. All patients were examined with activated ATPS for adaption of tube voltage to body habitus. 50 patients were scanned on a third-generation dual-source CT (DSCT), and another 50 patients on a second-generation DSCT. Predefined image quality setting remained stable between both groups at 120 kV and a current of 210 Reference mAs. Subjective image quality assessment was performed by two blinded readers independently. Attenuation and image noise were measured in several anatomic structures. Signal-to-noise ratio (SNR) was calculated. For the evaluation of radiation exposure, CT dose index (CTDIvol) values were compared.
RESULTS: Diagnostic image quality was obtained in all patients. The median CTDIvol (6.1 mGy, range 3.9-22 mGy) was 40 % lower when using the algorithm compared with the previous ATCM protocol (median 10.2 mGy · cm, range 5.8-22.8 mGy). A reduction in potential to 90 kV occurred in 19 cases, a reduction to 100 kV in 23 patients and a reduction to 110 kV in 3 patients of our experimental cohort. These patients received significantly lower radiation exposure compared to the former used protocol.
CONCLUSION: Latest generation automated ATPS on third-generation DSCT provides good diagnostic image quality in chest-abdomen-pelvis CT while average radiation dose is reduced by 40 % compared to former ATPS protocol on second-generation DSCT.
Das Unfertige im Bild
(2010)
Es war keine gezielte Suche, sondern Zufall, dass ich bei einem meiner Streifzüge durch die Londoner 'National Gallery' auf ein Gemälde des englischen Malers Thomas Gainsborough traf. Was zuerst meine Aufmerksamkeit an diesem Bild erregte, war ein Detail: ein anscheinend leeres, leicht gebogenes Blatt Papier, in der Hand gehalten von einer männlichen, am linken Rand des Bildes positionierten Figur. Das Papierblatt hatte etwas merkwürdig Stoffliches, Durchscheinendes und Schwebendes. Eine kleine Tafel, die direkt neben dem Ölgemälde an der Wand angebracht war, vermerkte den Titel und das Entstehungsdatum des Bildes: 'Portrait of the Artist with his Wife and Daughter, about 1748'. Gainsborough, 1727 geboren, hatte das Bild also als junger Künstler gemalt. Auf der kleinen Tafel fand sich zudem der folgende Text: "Gainsborough married Margaret Burr in 1746. The child is probably their first-born daughter, Mary, who died in March 1748. A second daughter was also named Mary. The hands of Mrs. Gainsborough are unfinished and the paper held by the artist is blank" (Abb. 1). Der letzte Satz dieses Kommentartextes verknüpfte die anscheinende Leere des Papierblatts, benannt als 'blankness', mit einem anderen Detail, das mir bis dahin noch gar nicht aufgefallen war, mit der nur in Umrissen erkennbaren rechten Hand der weiblichen Figur nämlich, einer in schwungvollen Pinselstrichen ausgeführten Form, deren Linien sich nur wenig vom blauen Stoff des Kleides, auf dem die Hand ruhte, abhoben. Die Blume, die diese Hand hielt, war dagegen präzise zu erkennen. Wies der Kommentartext auf der kleinen, neben dem Bild montierten Tafel die Darstellung 'beider' Hände der weiblichen Figur als 'unfinished' aus, so schien mir die gleichsam natürliche Unsichtbarkeit der linken Hand, die durch die Gestalt des stehenden Kindes verdeckt war, von ganz anderer Art zu sein als jener durch das Unfertige der rechten Hand erzeugte Modus einer Un/Sichtbarkeit, in der ganz offensichtlich - gegen die Darstellungsregel der exakten Naturnachahmung - etwas fehlte. Ein Fehlen, dessen Begriff unterstellte, dass hier noch etwas hätte kommen müssen. Ich hatte den Eindruck, dass dieses Unfertige im Bild eine wolkige Stelle markierte, genau im Sinn von Walter Benjamin: "die Stelle, wo es aufhört, durchsichtig zu sein."
Carmens Passion
(2010)
Carmen stirbt in der Stierkampfarena von Sevilla; doch die Geschichte ihrer Passion beginnt früher. Was Prosper Mérimée und Georges Bizet - als Novelle und Oper - gestaltet haben, ist ein Thema des 19. Jahrhunderts, dessen Wurzeln bis auf die Wände paläolithischer Kulthöhlen zurückverfolgt werden können.
Im Wesen des Menschen liegen, vor allem Wissen, die Stimmungen. Sie schwingen uns, wenn wir vernehmen, immer schon in ein Gefühltes ein, Freude oder Trauer, Mut, Verzweiflung, Leidenschaft. Wir freuen uns zwar am meisten über das, was unsere Augen sehen, weil es an den Dingen so viele Unterschiede entbirgt. In Wahrheit aber können wir nur lernen und daher wissen, weil Menschen, anders als zum Beispiel Bienen, auch Ohren haben. Weil der Mensch das nachahmendste von allen Tieren ist und Kinder ihr erstes Wissen nur durch Nachahmung von Älteren erwerben, sind Menschen die einzigen Tiere, die den Logos oder die Sprache haben.
Paul Klees 'Angelus Novus' setzt bei Benjamin eine Reflexion in Gang, die unter der Ziffer 9 in seiner Schrift "Über den Begriff der Geschichte" (1940) ihre letzte sprachliche Gestalt findet. Das Denkbild setzt sich zur Zeichnung abseits 'objektiver' Beschreibungen und gängiger Bildkritik ins Verhältnis. Benjamins methodologisches Plädoyer für die Verwandlung von "Dinge[n] und Werke[n] in erregende Schrift" führt zu einer Betrachtungsweise, der es gelingt, das materielle Bild in sinnlicher Präsenz zur Darstellung zu bringen, und zwar wiederum als - dialektisches - Bild, welches den Augenblick, in dem die aktuelle Lektüre mit dem Abstand der Zeit zusammentritt, stillstellt. Diese Kunst der Darstellung soll hier Anlass dafür sein, das Verhältnis von Benjamins Sprache zur Malerei als einem zweiten Medium zu beleuchten.
Im Folgenden werden einige Facetten dieses weiten Feldes [der Synästhesie] herausgegriffen, nämlich das der Farblichtmusik und der Verbindung von Ton und Bild zwischen 1920 und 1930 mittels apparativer Verschaltungen. Hierzu werden zwei technische Anordnungen gegenübergestellt, die eine Ton-Bild-Wandlung auf eine Weise vornahmen, die radikaler als die damals weit verbreiteten Lichtorgeln vorging, indem sie nicht nur metaphorisch mit der gleichschwingenden Kraft von Tönen und Bildern agierten, sondern diese zum Gegenstand medientechnischer Anordnungen machten. Die eine dieser Apparaturen wurde im Kontext der Kunst entwickelt und stammt von Raoul Hausmann, während die andere von dem Fernmeldetechniker Fritz Winckel realisiert wurde. Indem Hausmann und Winckel die Zuordnung von Tönen und Bildern nicht assoziativ realisierten wie die meisten Lichtorgeln dieser Zeit, sondern die Ton- und Bildquellen mit analoger Technik direkt verschalteten, riefen sie umso mehr den Vergleich mit der durch Menschen wahrgenommenen Synästhesie auf, weshalb zu Beginn auf diese etwas breiter eingegangen werden muss. Hier ist zu fragen, was geschieht, wenn Synästhesie zu einem künstlerischen Konzept wird und welche Rhetoriken von Kunstschaffen in den 1920er Jahren daran gebunden waren. Es soll deutlich werden, dass die vom Menschen wahrgenommene Synästhesie in ihrer körperlichen Grundlage sowie in ihrem ästhetischen Empfinden nicht mehr als eine Metapher für ihr medientechnisches Pendant sein konnte. Synästhetische Wahrnehmung und verschaltete Medien bringen jeweils ihre eigenen ästhetischen Reiche hervor. Andererseits boten die unscharfen und vielschichtigen Konzepte der Synästhesie zahlreiche Anregungen für Künstler, schufen Raum für eine Synthese der Künste und waren der Anstoß für neue künstlerische Ausdrucksformen mittels Medientechnik und damit eine frühe Form der Medienkunst.
Multimodal therapy of glioblastoma (GBM) reveals inter-individual variability in terms of treatment outcome. Here, we examined whether a miRNA signature can be defined for the a priori identification of patients with particularly poor prognosis.
FFPE sections from 36 GBM patients along with overall survival follow-up were collected retrospectively and subjected to miRNA signature identification from microarray data. A risk score based on the expression of the signature miRNAs and cox-proportional hazard coefficients was calculated for each patient followed by validation in a matched GBM subset of TCGA. Genes potentially regulated by the signature miRNAs were identified by a correlation approach followed by pathway analysis.
A prognostic 4-miRNA signature, independent of MGMT promoter methylation, age, and sex, was identified and a risk score was assigned to each patient that allowed defining two groups significantly differing in prognosis (p-value: 0.0001, median survival: 10.6 months and 15.1 months, hazard ratio = 3.8). The signature was technically validated by qRT-PCR and independently validated in an age- and sex-matched subset of standard-of-care treated patients of the TCGA GBM cohort (n=58). Pathway analysis suggested tumorigenesis-associated processes such as immune response, extracellular matrix organization, axon guidance, signalling by NGF, GPCR and Wnt. Here, we describe the identification and independent validation of a 4-miRNA signature that allows stratification of GBM patients into different prognostic groups in combination with one defined threshold and set of coefficients that could be utilized as diagnostic tool to identify GBM patients for improved and/or alternative treatment approaches.
Background: Erythema migrans represents an early cutaneous and most common manifestation of Lyme borreliosis. Recommendations regarding pharmacological agents, dose and duration of treatment are subject of intense debate. This review aims to explore differences in efficacy and safety between pharmacological treatments and control treatment.
Methods: To identify relevant studies, we will conduct a systematic literature search. We will include randomised controlled trials (RCTs) and non-RCTs. Eligible comparative studies need to (1) consider patients with a diagnosis of erythema migrans resulting from Lyme borreliosis and (2) compare different pharmacological agents against each other, against any other non-pharmacological treatment, placebo or no treatment. Two review authors will independently assess included studies for risk of bias according to the methods of the Cochrane Handbook for Systematic Reviews of Interventions and related to specific study designs. We will address patient-relevant outcomes including clinical remission of cutaneous symptoms, any treatment-related adverse events, quality of life and progressive symptoms such as neuroborreliosis or Lyme carditis and flu-like symptoms. Provided that the identified trials are comparable in terms of clinical issues, combined estimates will be provided. Estimations of treatment effects will be calculated based on a random effects model. Heterogeneity will be evaluated based on I (2) and chi-square test. In case of significant heterogeneity, a pooled estimate will not be provided, but heterogeneity will be investigated on the basis of methodological and clinical study aspects. We plan subgroup analysis to reveal potential differences in the effect estimates between patient populations and treatment specifications. We will consider risk of bias using sensitivity analyses to decide whether to rely on the pooled estimates. The quality of a body of evidence for individual outcomes will be assessed using the GRADE approach.
Discussion: Benefits and harms of pharmacological treatment in erythema migrans have not yet been adequately assessed. This systematic review will evaluate and summarise available evidence addressing benefits and harms of different pharmacological treatments. In addition, this summary of clinical evidence will inform decision-making between clinicians and patients and will play an important part in patient care.
Systematic review registration: PROSPERO: CRD42016037932.