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Konstitutionalisierung, Europäisierung, Internationalisierung … So viele bestehende oder sich abzeichnende Tendenzen, die durch ihre Neuheit bestechen und durch ihre Dynamik Interesse erwecken. Doch, wie Jean-Claude Gautron gerne seinen Doktoranden zu verstehen gibt, "nicht alles, was glänzt, ist Gold", eine Einstellung, die sich auch in seiner eigenen Haltung der "kritischen Betrachtung Europas durch einen Europarechtler" widerspiegelt. Ihn durch den Versuch zu würdigen, die Verwendung bestimmter Begriffe zu beleuchten, ist daher nicht unangemessen. ...
Gezielte Früherkennung am Beispiel des Deutschen Konsortiums Familiärer Brust- und Eierstockkrebs / Rita Schmutzler
Modelle für eine erfolgreiche, risikoadaptierte Therapie –
am Beispiel der akuten lymphatischen Leukämie / Nicola Gökbuget
Modelle für eine erfolgreiche, risikoadaptierte Therapie –
am Beispiel des Hodgkin-Lymphoms / Andreas Engert
Modelle für eine erfolgreiche, risikoadaptierte Therapie –
am Beispiel der Keimzelltumoren des Mannes / Carsten Bokemeyer
Holographic imaging techniques, which exploit the coherence properties of light, enable the reconstruction of the 3D scenery being viewed. While the standard approaches for the recording of holographic images require the superposition of scattered light with a reference field, heterodyne detection techniques enable direct measurement of the amplitude and relative phase of the electric light field. Here, we explore heterodyne Fourier imaging and its capabilities using active illumination with continuous-wave radiation at 300 GHz and a raster-scanned antenna-coupled field-effect transistor (TeraFET) for phase-sensitive detection. We demonstrate that the numerical reconstruction of the scenery provides access to depth resolution together with the capability to numerically refocus the image and the capability to detect an object obscured by another object in the beam path. In addition, the digital refocusing capability allows us to employ Fourier imaging also in the case of small lens-object distances (virtual imaging regime), thus allowing high spatial frequencies to pass through the lens, which results in enhanced lateral resolution.
L’arrêt Lüth – 50 ans après
(2019)
Même 50 ans plus tard, l’arrêt Lüth, rendu par la Cour constitutionnelle fédérale le 15 janvier 1958, n’a rien perdu de son actualité. Il confère durablement à la liberté d’expression un rang primordial pour le débat public démocratique et marque le point de départ du développement d’une dogmatique des droits fondamentaux spécifiquement allemande, à l’origine d’un renforcement des compétences et de la puissance particulières de la Cour constitutionnelle fédérale. Les raisons qui expliquent l’approche particulière de résolution de conflits entre droits suivie dans l’arrêt Lüth ne laissent pas présager un abandon de cette jurisprudence, abandon qui ne serait d’ailleurs ni souhaitable ni réaliste.
Le constitutionnalisme est un phénomène relativement récent dans l’histoire des institutions politiques. Il a émergé au cours des vingt-cinq dernières années du XVIIIe siècle, à la suite de deux révolutions menées avec succès contre le pouvoir en place, la première dans les colonies anglaises d’Amérique du Nord, la seconde en France. Immédiatement perçu comme une avancée majeure, le constitutionnalisme n’a pas tardé à exercer également son pouvoir d’attraction en dehors des pays où il est apparu. Partout en Europe, et ensuite dans d’autres parties du monde, des tentatives pour mettre en place des constitutions modernes virent le jour. Tout le XIXe siècle fut traversé par les luttes pour une constitution, et le XXe siècle fut une période de sérieux revers, avant qu’au tournant du XXIe siècle, le constitutionnalisme ne finisse par accéder à une reconnaissance mondiale. De nos jours, seule une poignée d’États, parmi les quelque deux cents que compte le monde, ne possède pas de constitution. ...
Here we present a comprehensive attempt to correlate aragonitic Na∕Ca ratios from Desmophyllum pertusum (formerly known as Lophelia pertusa), Madrepora oculata and a caryophylliid cold-water coral (CWC) species with different seawater parameters such as temperature, salinity and pH. Living CWC specimens were collected from 16 different locations and analyzed for their Na∕Ca ratios using solution-based inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements.
The results reveal no apparent correlation with salinity (30.1–40.57 g kg−1) but a significant inverse correlation with temperature (−0.31±0.04 mmolmol−1∘C−1). Other marine aragonitic organisms such as Mytilus edulis (inner aragonitic shell portion) and Porites sp. exhibit similar results highlighting the consistency of the calculated CWC regressions. Corresponding Na∕Mg ratios show a similar temperature sensitivity to Na∕Ca ratios, but the combination of two ratios appears to reduce the impact of vital effects and domain-dependent geochemical variation. The high degree of scatter and elemental heterogeneities between the different skeletal features in both Na∕Ca and Na∕Mg, however, limit the use of these ratios as a proxy and/or make a high number of samples necessary. Additionally, we explore two models to explain the observed temperature sensitivity of Na∕Ca ratios for an open and semi-enclosed calcifying space based on temperature-sensitive Na- and Ca-pumping enzymes and transport proteins that change the composition of the calcifying fluid and consequently the skeletal Na∕Ca ratio.
Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome characterized by bilateral myoclonic and tonic-clonic seizures typically starting in adolescence and responding well to medication. Misdiagnosis of a more severe progressive myoclonus epilepsy (PME) as JME has been suggested as a cause of drug-resistance. Medical records of the Epilepsy Center Hessen-Marburg between 2005 and 2014 were automatically selected using keywords and manually reviewed regarding the presence of a JME diagnosis at any timepoint. The identified patients were evaluated regarding seizure outcome and drug resistance according to ILAE criteria. 87/168 identified JME patients were seizure-free at last follow-up including 61 drug-responsive patients (group NDR). Seventy-eight patients were not seizure-free including 26 drug-resistant patients (group DR). Valproate was the most efficacious AED. The JME diagnosis was revised in 7 patients of group DR including 6 in whom the diagnosis had already been questioned or revised during clinical follow-up. One of these was finally diagnosed with PME (genetically confirmed Lafora disease) based on genetic testing. She was initially reviewed at age 29 yrs and considered to be inconsistent with PME. Intellectual disability (p = 0.025), cognitive impairment (p < 0.001), febrile seizures in first-degree relatives (p = 0.023) and prominent dialeptic seizures (p = 0.009) where significantly more frequent in group DR. Individuals with PME are rarely found among drug-resistant alleged JME patients in a tertiary epilepsy center. Even a very detailed review by experienced epileptologists may not identify the presence of PME before the typical features evolve underpinning the need for early genetic testing in drug-resistant JME patients.
Physiologie des Menschen
(2019)
Wir haben mit diesem Lehrbuch eine Brücke zwischen den "dicken Wälzern", die viele Dozenten empfehlen, und den Kurzlehrbüchern, die bei Studenten so beliebt sind, geschlagen. Physiologie ist ein Fach, das man verstehen muss. Denn gerade in mündlichen Prüfungen und im Physikum werden Transferleistungen eingefordert, die sich durch reines Auswendiglernen nicht ohne Weiteres lösen lassen. Im Gegensatz zu Kurzlehrbüchern findest du bei uns mehr Erklärungen, die dir beim Verständnis der Zusammenhänge helfen. Damit unser Buch nicht zu dick und unübersichtlich wird, haben wir all den Ballast, den du in den "dicken Wälzern" findest, weggelassen. Das hilft dir, dich auf die wichtigen Dinge zu konzentrieren. Diese wichtigen Dinge erklären wir dafür ausführlicher. Unser Buch ist daher der ideale Begleiter für die vorklinischen Semester, weil alle relevanten Themenkomplexe einfach und verständlich erklärt werden. Je nach Universität kann es natürlich vorkommen, dass speziellere Themen gelehrt werden, die nicht unbedingt dem Lernzielkatalog entsprechen. Diese Themen sind in unserem Buch unter Umständen nicht oder nur knapp erwähnt. Wir empfehlen dir deshalb, die Vorlesungen deiner Universität zu besuchen, damit du genau weißt, worauf deine Dozenten wert legen. ...
In this review a summary is given on recent theoretical work, on understanding accreting supermassive black hole binaries in the gravitational wave (GW)-driven regime. A particular focus is given to theoretical predictions of properties of disks and jets in these systems during the gravitational wave driven phase. Since a previous review by Schnittman 2013, which focussed on Newtonian aspects of the problem, various relativistic aspects have been studied. In this review we provide an update on these relativistic aspects. Further, a perspective is given on recent observational developments that have seen a surge in the number of proposed supermassive black hole binary candidates. The prospect of bringing theoretical and observational efforts closer together makes this an exciting field of research for years to come.
Uni-Highlights Januar 2020 : Einladungen zu ausgewählten Veranstaltungen der Goethe-Universität
(2019)
Infrastrukturen sind die Basis jeder Form wissenschaftlicher Forschung. Was aber bedeutet der Einsatz von digitalen Infrastrukturen für die Ermöglichung und Fortentwicklung der digitalen Geisteswissenschaften konkret? Die Beiträge des Bandes sind anlässlich des Symposium "Forschungsinfrastrukturen in den digitalen Geisteswissenschaften. Wie verändern digitale Infrastrukturen die Praxis der Geisteswissenschaften?" im Jahr 2018 entstanden und nehmen sowohl digitale Infrastrukturen in den Geisteswissenschaften wie auch Infrastrukturen für die digitalen Geisteswissenschaften in den Blick.
This doctoral thesis deals with the structural and dynamical NMR characterization of biomolecules, covering a broad range of proteins, from small peptides to large GPCRs proteins. This work consists of two projects, which are presented in chapter II and III. Chapter II is focused on the structural screening of peptides and small proteins ranging from 14 to 71 amino acids, while chapter III describes the structure and light dynamics of the disease relevant rhodopsin G90D mutant. The main method used to investigate both types of proteins is NMR spectroscopy. Both chapters comprise individual general introduction, materials and methods, results and discussion sections, and a final conclusion paragraph.
‘Chapter I: Methodological aspects of protein NMR spectroscopy’ presents an overview of different NMR methods developed for the rapid characterization of protein structure and dynamics. Multidimensional NMR, which is routinely used in structural biology, is indispensable for protein structure determination in solution. However, detailed information with resolution at the atomic level is time consuming and requires weeks of expensive measurement time, followed by the manual data analysis. Therefore, the development of time-saving NMR techniques is highly required for screening studies of a large amount of proteins, and can be also helpful for studying unstable biomolecules, as their short lifetime often restricts the experimental procedure.
This chapter covers the two main approaches to accelerate a multidimensional NMR experiment: fast-pulsing techniques that aim to reduce the duration of an individual measurement, and non-uniform sampling technique (NUS), which was developed to reduce the overall number of increments in virtual time domains. A combination of both approaches, fast-pulsing and non-uniform sampling, allows speeding up the measurement time by 2-3 orders of magnitude. Furthermore, recently developed software called TA (targeted acquisition) combines various time-saving approaches, including fast-pulsing, non-uniform sampling and targeted acquisition. Targeted acquisition algorithm records a set of multidimensional NMR spectra in semi-interleaved incremental mode. This provides the ability to monitor the quality of the recorded spectra in real-time and therefore enables the completion of the experiments after the desired quality is achieved. Using this approach will greatly reduce the measurement time without losing important structural information. The implemented automated FLYA assignment further contributes to the rapid and simplified readout of the chemical shift assignment progress of the TA program. During this doctoral dissertation, the scientific collaboration with the TA software developer Prof. Vladislav Orekhov (Sweden) took place, and resulted in the successful establishing of this new NMR technology in the Schwalbe laboratory. TA is now routinely applied in Prof. Schwalbe group for the structure elucidation of small proteins.
‘Chapter II: Rapid NMR and biophysical characterization of small proteins’ describes the structural analysis of peptides and small proteins, which were recently identified within the framework of the Priority Program (SPP 2002). Due to technical limitations in detections of small systems and strict assumptions concerning the smallest size of the gene that can be translated, small open reading frames (sORFs) were excluded from the automated gene annotation for a very long time. Thanks to the newly developed computational and experimental approaches, the ability to identify and detect the small proteins consisting of less than approximately 70 amino acids sparked a growing scientific interest by microbiologist. In the past years, hundreds of new short protein sequences were discovered. Although some peptides were found to be involved in diverse essential biological processes, the functional elucidation of a large number of recently discovered peptides and small proteins remains a challenging task. It is well established that the structure of proteins is often linked to their function. However, the size of small constructs often restricts the possible diversity of secondary structure elements that might be adopted by a protein. Furthermore, as was shown for intrinsic discorded proteins (IDPs), the absence of a well-defined three-dimensional structure does not necessarily mean lack of function. Moreover, peptides, which are initially unstructured in the isolated form can fold in a stable structured conformation upon interaction with their biological partners. Solution state NMR spectroscopy is perfectly amenable for the structural characterization of systems of this size. It provides a rapid readout about the conformational state of small peptides unambiguously, distinguishing between folded, molten globule and unstructured conformations.
During this doctoral thesis the workflow protocol for fast screening of peptides and small proteins was established and applied to 20 candidates ranging from 14 to 71 amino acids, which were identified and selected by six microbiological groups, all members of the Priority Program on small proteins (SPP2002) funded by the German research foundation (DFG). The screening protocol includes sample preparation and biochemical characterization. Peptides containing less than 30 amino acids were synthesized by solid phase synthesis (SPPS), while small proteins containing more than 30 amino acids were heterologously expressed in E. coli.
...
Das kolorektale Karzinom ist eine der am häufigsten vorkommenden Tumorerkrankung weltweit. In den letzten Jahren wurden viele molekulare Zusammenhänge in der Entstehung des kolorektalen Karzinoms entdeckt. Aus diesen Erkenntnissen konnten neue Therapiemöglichkeiten entwickelt werden. Aktuell werden im europäischen Raum die UICC-Stadien zur Einschätzung der Tumoraggressivität angewandt um die bestmöglichen Therapieoptionen zu gewährleisten.
In der hier vorgestellten Arbeit konnte bei einem Kollektiv von 195 Patienten mit kolorektalen Karzinomen gezeigt werden, dass an H.E.-Schnitten morphologische Phänomene wie Tumor Budding und bestimmte morphologisch fassbare Veränderungen in der Tumorumgebung (Mikroenviroment, epithelialmesenchymale Transition) signifikant und zuverlässig diagnostiziert werden können und davon abgeleitet die Aggressivität eines kolorektalen Karzinoms eingeschätzt werden kann.
Hierbei wurden alle Fälle, bei denen eine Tumoreinzelzelle bzw. ein Zellcluster mit weniger als fünf Zellen mikroskopiert werden konnte, in die Gruppe der Tumorbudds aufgenommen. Der Nachweis von Tumorbudds war ein unabhängiger Marker auf eine systemische Tumorausbreitung.
Es fand sich überdurchschnittlich häufig ein Zusammenhang zwischen Tumor Budding und schlechteren Überlebensraten sowie einer fortgeschrittenen Tiefeninfiltration (höhere pT-Stadien), Lymphknoten- oder Fernmetastasen bzw. hohen UICC-Stadien III/IV.
Ein weiteres Hauptaugenmerk wurde auf morphologische Veränderungen des Mikroenviroments und hierbei insbesondere auf die Fibroblasten des den Tumor umgebenden Bindegewebes sowie Zellen des Immunsystems, u.a. Lymphozyten und Makrophagen gelegt. Es konnte ein signifikanter Zusammenhang einer fibroblastenreichen Umgebungsreaktion mit wenigen Makrophagen und Lymphozyten und einem positiven Lymphknotenstatus oder hohen UICC Stadien III/IV gezeigt werden.
Beim Vergleich der Umgebungsreaktion mit dem Tumor Budding wurden in Bezug auf den Lymphknotenstatus und dem UICC-Stadium signifikant häufiger eine fibroblastenreiche Reaktion in Kombination mit einem Tumor Budding als eine Gewebsreaktion in Kombination mit Tumor Budding bei Tumoren mit Lymphknotenmetastasen bzw. hohen UICC-Stadien III/IV nachgewiesen.
Vergleichende Untersuchungen zwischen den oben beschriebenen morphologischen Veränderungen und Mutationen des Exon 2 im KRAS-Gen blieben ohne eine statistische Signifikanz. Der Vergleich der Sequenziermethode nach Sanger mit der Pyrosequenzierung ergab eine geringfügig höhere Sensitivität für die Sangersequenzierung, wenngleich ohne statistische Signifikanz.
Die Ergebnisse der hier vorgelegten Arbeit bestätigen die hohe Wertigkeit des Tumor Buddings und der Umgebungsreaktion des Tumors für die Einschätzung der Tumoraggressivität. Die Veränderungen sind einfach an H.E.-Routineschnitten zu diagnostizieren. Diese morphologischen Veränderungen spiegeln wahrscheinlich den entscheidenden Übergang eines lokal aggressiv wachsenden Tumors in einen Tumor mit Lymphknoten- und Fernmetastasierung wieder. Möglicherweise spielt die Interaktion zwischen Fibrozyten/blasten und ortsständigen oder eingewanderten Makrophagen eine wichtigere Rolle in der körpereigenen Tumorabwehr als bisher angenommen.
Knowledge about the herbaceous layer in relation to environmental factors in West African savannas is still scarce. Early life-cycle events like germination of the herbaceous species are of special interest, as these stages can play critical roles in establishing of the plants and determine population and community dynamics. We aim to assess intraspecific differences in the germinability of herbaceous savanna species with respect to environmental conditions to reveal adaptations in this early life cycle stage. The study was conducted in the Sudanian savanna of Burkina Faso in West Africa. We collected seeds of two annual herbs (Chamaecrista mimosoides, Spermacoce stachydea) along a climatic gradient from different habitats and land use types and conducted germination experiments under equal conditions in climate chambers. For both species several environmental factors showed a significant impact on the germination rates. While higher precipitation caused an increase in the germination rate only for S. stachydea, habitat conditions had a significant influence for both species. Intermediate habitats with balanced soil moisture caused an enhancement of the germination success. Moreover shrub cover had a positive effect on the germinability of C. mimosoides, whereas the germinability of S. stachydea decreased due to an increasing herbaceous cover. The study showed that certain environmental factors are able to modify the intraspecific variability of the germinability trait, which might affect the establishment of the species populations.
Cette étude avait pour objectifs: 1) d’identifier et de caractériser les acteurs impliqués dans la filière des produits à usage médicinal tirés de Cordyla pinnata, Detarium microcarpum et Detarium senegalense au Sénégal; 2) d’analyser l’organisation de cette filière et l’importance des parties utilisées; 3) d’analyser la commercialisation de ces produits; 4) d’identifier les forces, faiblesses, opportunités et menaces de la filière. L’échantillonnage en boule de neige a été utilisé et a permis d’interroger, à l’aide de guides d’entretien 13 tradipraticiens locaux, 3 récolteurs et 17 herboristes. Les résultats ont révélé que les acteurs de cette filière, majoritairement des hommes, entretenaient des relations de coopération et qu’ils béné- ficiaient de l’appui de la société civile en termes de formation et d’organisation. Les racines et les écorces de Cordyla pinnata et Detarium microcarpum étaient plus utilisées tandis que celles de Detarium senegalense étaient peu commercialisées. Les écorces, les racines et les feuilles étaient vendues entre 0,108 et 0,290 Euro/100g. Une partie des écorces était transformée en poudre avant d’être commercialisée chez les herboristes entre 1,046 Euro/100g (pour Cordyla pinnata) et 1,524 Euro/100g (Detarium microcarpum). Les prix étaient plus élevés à Dakar. Les parties tirées de Cordyla pinnata étaient essentiellement utilisés contre les parasitoses intestinales tandis que celles de Detarium microcarpum et dans une moindre mesure celles de Detarium senegalense servaient à soigner les dermatoses. Les faiblesses de cette filière concernaient essentiellement l’exploitation anarchique de la ressource et la raréfaction saisonnière de certains produits tandis que l’éloignement des sites d’approvisionnement menaçait son bon fonctionnement.
Carapa procera is a wild oil tree species traditionally exploited in Mali for seed oil. Carapa oil is highly sought because of therapeutic, cosmetic, insecticidal and repellent properties. The purpose of this work was to contribute to the understanding of local practices in carapa oil production and local perceptions related thereto. The method used was based on surveys in four production localities and tests of oil production according to the traditional processes practiced by the processors. Two methods of seed storage and oil extraction processes were identified. Women were the main actors in seed collection and oil processing. The average oil extraction efficiency from the seeds was 23.1% and varied among sites. The wet extraction process was the most efficient. In addition to socio-cultural considerations, difficulties related to technology (lack of adequate extraction equipment) and the decrease of carapa populations limit the full development of processing acti- vities. It is necessary to undertake options to improve traditional oil production processes such as education and introduction of shea presses in order to reduce labour intensity, improve efficiency and ensure quality standards. It also requires action for the sustainable management and conservation of the carapa species.
Au Burkina Faso, les unités d’aménagements forestiers (UAFs) sont confrontées à une forte pression anthropique qui cause la dégradation des ressources ligneuses dont Vitellaria paradoxa est l’une des espèces surexploitées. Afin de con- tribuer à la gestion durable de ces UAFs, il s’avère nécessaire d’analyser l’impact des pressions anthropiques sur la phytodi- versité et la dynamique de Vitellaria paradoxa. Ainsi, des facteurs tels que l’agriculture, la coupe illégale de bois, le pâturage et les feux non autorisé ont été évalués dans l’UAF 2, l’UAF B et l’UAF C, où des inventaires forestiers ont été conduits. Les résultats montrent que le pâturage et les feux non autorisé ont été les facteurs les plus fréquents dans les UAFs, sur- tout dans l’UAF C (> 90%) alors que les autres facteurs ont été plus abondants dans l’UAF 2. La phytodiversité mesu- rée est presque similaire dans les trois UAFs avec toutefois des indices de diversité plus élevés dans l’UAF 2. La struc- ture de Vitellaria paradoxa montre une prédominance d’individus jeunes dans les UAFs et des densités plus élevées dans l’UAF C tandis que sa régénération est plus importante dans l’UAF 2. L’état sanitaire de l’espèce est globalement satis- faisant bien que la principale menace soit l’infestation des Loranthaceae qui a été plus importante dans l’UAF 2 (7%). L’exploitation durable des UAFs nécessite la mise en œuvre d’un programme de conservation avec une forte implication des populations riveraines.
Die Differenzierung zwischen Teilpopulationen hin zu unterschiedlichen Arten kann nur erfolgen, wenn zwischen diesen Teilpopulationen reproduktive Isolation besteht. Wie die unterschiedlichen Arten von reproduktiver Isolation zusammenwirken und welche Voraussetzungen bestehen müssen, um neue Arten zu bilden, muss in jedem Studiensystem untersucht werden. Ein idealer Ansatzpunkt sind Arten, die sich mehrfach an anspruchsvolle Habitate angepasst haben, deren Artbildung also von ökologischen Habitatparametern bestimmt wird. Dieser Vorgang wird als Ökologische Artbildung bezeichnet. Im Artkomplex Poecilia spec., der im Süden Mexikos mehrere schwefelangepasste Ökotypen ausgebildet hat, wurden erste Hinweise auf eine Korrelation zwischen der Selektionsstärke von natürlicher und sexueller Selektion gefunden, deren Einfluss zusammen die bestehenden reproduktiven Barrieren zwischen Klarwasser- und Schwefelökotyp formen. Wie diese Reproduktionsbarrieren beschaffen sind und wie die Umweltvariable Schwefel auf die Morphologie und das Verhalten der Poeciliiden Einfluss nimmt, wurde in der vorliegenden Arbeit anhand von fünf Fragestellungen untersucht. (1) Die Körperfärbung kann ein aussagekräftiges Signal für die Qualität des potentiellen Partners bei der Fortpflanzung sein. Wie beeinflusst die extreme Umweltvariable Schwefel die Ausbildung von Färbung? (2) Sind die gefundenen Anpassungen der Färbung erblich oder werden sie plastisch entsprechend des Nahrungsangebots ausgebildet? (3) In einem der untersuchten Flusssysteme konnte unvollständige reproduktive Isolation zwischen der Klarwasser- und Schwefelpopulation nachgewiesen werden. Sind in den Mischzonen zwischen diesen beiden Habitaten Hybriden genetisch nachweisbar und bilden diese die Färbungsanpassungen der Klarwasser-, der Schwefelpopulation oder eine intermediäre Form aus? (4) Die Gelbfärbung der Flossen bei Männchen scheint ein geeignetes Merkmal für die Anzeige der Qualität zu sein, da es möglicherweise unabhängig vom Nahrungsangebot ausgebildet wird. Besteht eine weibliche Präferenz für dieses Merkmal? (5) Auch die weibliche Partnerwahlpräferenz wird vom Habitat und dem eigenen Zustand beeinflusst. Wie verändert sich die Präferenz für Männchen mit gutem Ernährungszustand bei Weibchen, die hungrig sind?
Um diese Fragen zu beantworten, wurden in mehreren Jahren Männchen und Weibchen der Arten Poecilia mexicana und Poecilia sulphuraria aus sieben Populationen im Studiengebiet in Südmexiko gefangen und auf ihre Färbung untersucht sowie Laborpopulationen getestet. Es konnten generelle Anpassungen der Färbung an die Umweltvariable Schwefel nachgewiesen werden. Dazu gehören die Aufhellung der Körperregionen, die durch Tarnung (konkret: countershading und background matching) vor Entdeckung durch Prädatoren schützen, und die Reduktion von Gelb- und Rottönen. Diese Anpassung ist vermutlich auf das geringe Angebot an Karotinoiden in den schwefelbelasteten Extremhabitaten zurückzuführen. Außerdem konnten zahlreiche flusssystem¬spezifische Anpassungen beschrieben werden, deren Ursachen in den Unterschieden zwischen den Schwefelhabitaten untereinander begründet sind. Das Flusssystem des Río Tacotalpa stellt hier eine Besonderheit dar, da Männchen eine besonders starke Gelbfärbung der Flossen aufweisen. Wildgefangene und laborgeborene Männchen dieses Flusssystems wurden verglichen, um einen Hinweis auf den Einfluss des Nahrungsangebots auf dieses Merkmal zu untersuchen. Tatsächlich ist die Ausprägung dieses Merkmals, die Gelbfärbung der Flossen, unabhängig vom Angebot an Karotinoiden. Während die hier verwendeten genetischen Analysen nicht geeignet waren, Hybriden aus den Mischzonen zwischen Schwefel- und Klarwasserhabitat nachzuweisen, ergaben die Untersuchungen von Individuen aus den Mischzonen keine eindeutigen Ergebnisse über eine etwaige intermediäre Ausbildung der Färbung. Die Präsentation von Männchen, deren Gelbintensität an den Flossenspitzen künstlich verändert wurde, konnte bei Weibchen keine eindeutige Präferenz für stärker gefärbte Männchen aufzeigen. Vielmehr weist dieses Ergebnis auf eine starke Korrelation zwischen mehreren Merkmalen (z. B. weitere morphologische Merkmale, Verhalten) hin, die für die Beurteilung der männlichen Qualität herangezogen werden. Die weibliche Präferenz für konditionsabhängige Merkmale wird bei schwefelangepassten Weibchen leicht verstärkt, wenn diese hungrig sind. Eine solche flexible Präferenz sollte gerade in Habitaten mit starken Fluktuationen im Nährstoffangebot existieren. Dabei waren Weibchen, denen Videoaufnahmen präsentiert wurden, eher in der Lage, das qualitativ hochwertigere Männchen zu identifizieren, als Weibchen, denen animierte Bilder präsentiert wurden. Auch hier wird davon ausgegangen, dass die Reduktion auf eines oder wenige Merkmale, die für die Partnerwahl zur Verfügung stehen, keine ausreichend starke Reaktion auslösen können. Vielmehr ist der Zugriff auf alle Aspekte der männlichen Erscheinung wichtig, um die Qualität des potentiellen Partners zu beurteilen.
Färbung ist also generell geeignet, den Ökotyp eines Individuums zu bestimmen und ein solches Merkmal kann der Artbestimmung im ersten Schritt der Partnerwahl dienen. Dasjenige männliche Färbungsmerkmal, das über mehrere Generationen gleichbleibend ausgeprägt wurde – die Gelbfärbung der Flossen – reicht jedoch nicht aus, um bei der weiblichen Partnerwahl eine Reaktion auszulösen. Vielmehr deuten die Ergebnisse auf eine enge Korrelation der Färbung mit weiteren Merkmalen in Morphologie und Verhalten eines Individuums hin, die vom wählenden Weibchen stets gemeinsam entsprechend der Multiple-message-Theorie betrachtet werden. Auch der Vergleich zwischen Videoaufnahmen und animierten Fotografien als Stimuli bei der Partnerwahl ergab, dass der Aspekt Verhalten (nur verfügbar mit Videoaufnahmen) für eine Partnerwahlentscheidung von Bedeutung ist.
Meine Arbeit konnte den bestehenden Wissensschatz um die bestehenden reproduktiven Barrieren im Studiensystem um den Aspekt der Färbung erweitern. Meine Ergebnisse zeigen weitere spannende Fragestellungen auf. Je größer das Verständnis der vorliegenden Selektionskräfte und Mechanismen reproduktiver Isolation ist, desto besser kann die Wissenschaft verstehen, welche Umgebungsvariablen welchen Einfluss auf den Prozess der Artbildung haben.
Malaria is an environmental disease, influenced not only by physical and biological environmental factors but also by socio-cultural ones. These factors affect each other, and, in turn, cause the disease in endemic areas. Some factors that cause the high morbidity rate associated with the disease include climate change, physical environment that varies geographically, socio-economic circumstances, and human behaviour in the affected areas. Other risk factors include housing conditions and poor sanitation, lack of hygiene practices, and inadequate health services in endemic areas. Efforts to eliminate malaria have been a topic at various public health meetings for decades. However, in Indonesia, malaria continues to be one of the leading causes of morbidity and mortality. The research aimed to analyse and model the critical variables associated with malaria in endemic areas of Indonesia. So, this included relationships between malaria and both socio-demographic variables and physical environments. The research is in three parts, adding value to a model that determines malaria in Indonesia.
This dissertation follows a cross-sectional design survey. The research data in this PhD dissertation is drawn from four sources: routine reporting of malaria from provincial health departments in South Sumatra; the national basic health research data (IDN acronym: Riskesdas); climate data from the Meteorology, Climatology, and Geophysics Climatological Agency (IDN acronym: BMKG); spatial data from Geospatial Information Agency (IDN acronym: BIG). This study takes a holistic approach, integrating the following univariate, bivariate, and multivariable logistic regressions, to establish a modelling determinant of malaria. Additionally, the researchers compared the performance of both Geographically Weighted Regression (GWR) and Ordinary Least Square (OLS). It also used some statistical analysis software tools for data processing, analysis, visualisation, and the development of the model as follows: Statistical Package for the Social Sciences (SPSS), Stata, Aeronautical Reconnaissance Coverage Geographic Information System (ArcGIS) 10.3, and GWR 4.0 version 4.0.90 for Windows.
The prevalence of malaria varied according to the local area, which, in turn, was related to the local physical environment that varied geographically. The determinants for malaria cases varied locally and regionally as well. Rural areas with a high percentage of households keeping livestock/pets showed a higher proportion of malaria prevalence than the national average. Other socio-demographic risk factors included gender, age, occupation, knowledge about healthcare, protection against mosquito bites, and condition of dwellings. This study reveals that the independent variables - "rainfall", "altitude", and "distance from mosquito resting sites in the forest," in global OLS analysis- are significantly associated with malaria cases in South Sumatra, Indonesia.
On the other hand, in the GWR analysis, the determinants of malaria cases at the village level vary geographically. Therefore, it is essential for the decision maker, the government, to acquire a more in-depth understanding of region-specific, ecological factors that influence confirmed malaria cases. The findings lead to the recommendation for developing sustainable regional malaria control programs and incentivising malaria elimination efforts, particularly at the village level. In another setting, the research led to the conclusion that the presence of mid-sized livestock comprised a significant risk factor for contracting malaria in rural Indonesia. The recommendation, especially for the study area, is to employ integrated vector management (IVM), for example, the simultaneous implementation of insecticide-treated bed nets (ITNs) and insecticide-treated livestock (ITL). Other factors such as socio-demographic and use of health care facilities were also crucial as they related to malaria prevalence. Further, the research leads to the recommendation for increased education and increased promotion and utilisation of the health care framework to promote knowledge and awareness of villagers on how to protect themselves from Anopheles bites. Finally, improving information concerning the availability of health care services and access to various health facilities in endemic areas is essential.
Die Kenntnis der Struktur von Biomolekülen und der biologischen Abläufe, in welche diese involviert sind, ist grundlegend für die Entwicklung von medizinischen Behandlungen. Im Rahmen dieser Arbeit wurden Systeme zur Untersuchung von Biomolekülen, insbesondere Proteinen, hergestellt. Im Mittelpunkt stand die Entwicklung von Materialien, welche neue Möglichkeiten zur Präparation von Proteinen zur Untersuchung derer Struktur mittels Kryo-Transmissionselektronenmikroskopie (Kryo-TEM) eröffnen. In zwei weiteren Projekten wurden biomimetische Systeme aufgebaut, welche die Oberfläche eines Biomoleküls oder biologischen Ensembles nachahmen und hierdurch deren Untersuchung ermöglichen. Hier wurden Systeme zur einfachen Nachbildung biologischer Membranen oder Proteinoberflächen betrachtet.
Eine wichtige Methode zur Untersuchung der dreidimensionalen Struktur von Biomolekülen ist die Kryo-TEM. Zur Mikroskopie werden die Biomoleküle in wenige Mikrometer großen Löchern eines amorphen Kohlenstofflochfilms mittels einer wenige Nanometer dicken Schicht aus amorphem Eis fixiert. Hierfür wird ein dünner Film einer wässrigen Probe auf den Kohlenstofflochfilm aufgebracht und gefroren. Insbesondere für Membranproteine ist die Herstellung derartiger Proben schwierig, da die Proteinpartikel zur Aggregation und Adsorption an dem Kohlenstofflochfilm neigen, wodurch keine Partikel in den Löchern des Kohlenstofffilmes auftreten, welche mikroskopiert werden können.
In dieser Arbeit wurden Materialien zur Verbesserung der Präparation von Proteinen für die Kryo-TEM entwickelt. Es wurden hierfür verschiedene biorepulsive Materialien, auch solche, welche eine spezifische Anbindung der Biomoleküle erlauben, untersucht. Da in der TEM die Probe durchstrahlt wird, eignen sich Nanometer dünne Membranen dieser Materialien als Trägermaterial für die Biomoleküle, da sie nur zu einem geringen Hintergrund führen. Zum einen wurden Nanomembranen durch die chemische Quervernetzung von Nanometer dicken Hydrogelfilmen mit verschiedenen quervernetzenden Molekülen hergestellt. Zum anderen wurden Trägerfilme, wie amorphe Kohlenstofffilme oder Kohlenstoffnanomembranen (engl. carbon nanomembranes, CNM) biorepulsiv funktionalisiert. Darüber hinaus wurde eine Nitrilotriessigsäure(NTA)-funktionalisierte Hydrogel-beschichtete Nanomembran entwickelt, welche markierte Proteine selektiv über einen His-Tag bindet.
Neben der Entwicklung von Materialien zur Untersuchung von Proteinen mittels Kryo-TEM wurden Beschichtungen hergestellt, welche die Oberfläche eines Biomoleküls oder eines Ensembles von Biomolekülen nachahmen. Diese Modelloberflächen sollten ebenfalls die Untersuchung von Eigenschaften der biologischen Systeme ermöglichen. Biologische Membranen bestehen aus einem Ensemble von Biomolekülen. Eine Vielzahl verschiedener Biomolekülen tritt in einer komplexen Anordnung in diesen dünnen Membranen auf. Es wurde versucht, strukturierte Membranen mit lokalen Variationen der physikalischen und chemischen Eigenschaften, jedoch weitaus weniger komplexen Aufbau, herzustellen. Die hergestellten Membranen mit biologisch relevanten Strukturen im Mikrometer- bis Zentimeterbereich, können nach weiterer Forschung als einfache Modellsysteme zur Nachahmung ihrer komplexen biologischen Vorbilder dienen.
In einem weiteren Projekt wurde eine Modelloberfläche für die Bindungstasche des Proteins FimH, welches eine wichtige Rolle in der bakteriellen Adhäsion spielt, entwickelt. In dem Kooperationsprojekt mit der Arbeitsgruppe Lindhorst wurde ein Modellsystem entwickelt, welches dazu dient, herauszufinden, inwiefern eine Funktionalisierung einer Aminosäurevon FimH über eine vorgeschlagenen Ligationsstrategie möglich ist. Das Modellsystem besteht aus einer biorepulsiven Hydrogel-Matrix, aus welcher die Seitenkette der Aminosäure Tyrosin in die Lösung exponiert ist. Die Substrat-katalysierte Reaktion der Aminosäuren-Seitenkette mit dem Photoschalter wurde mithilfe eines Bakterienadhäsionstests untersucht. Es konnte gezeigt werden, dass sich die vorgeschlagene Ligationsstrategie unter Berücksichtigung von Nebenreaktionen zur Modifizierung des Proteins eignet.
Es konnten vier neuartige Systeme, welche die Probenpräparation zur Untersuchung von Proteinen mittels Kryo-TEM vereinfachen, entwickelt werden. Die Ergebnisse sind von wissenschaftlicher Relevanz, da sie die Strukturbestimmung vieler Proteine deutlich vereinfachen und hierdurch beschleunigen können. Außerdem wurden biomimetische Beschichtungen entwickelt, welche entweder Proteinoberflächen oder Biomembranen nachahmen. Die entwickelten Modellsysteme erweitern das Spektrum an Möglichkeiten, Biomoleküle oder biologische Ensembles zu untersuchen.
Multimodal quantitative mri reveals no evidence for tissue pathology in idiopathic cervical dystonia
(2019)
Background: While in symptomatic forms of dystonia cerebral pathology is by definition present, it is unclear so far whether disease is associated with microstructural cerebral changes in idiopathic dystonia. Previous quantitative MRI (qMRI) studies assessing cerebral tissue composition in idiopathic dystonia revealed conflicting results.
Objective: Using multimodal qMRI, the presented study aimed to investigate alterations in different cerebral microstructural compartments associated with idiopathic cervical dystonia in vivo.
Methods: Mapping of T1, T2, T∗2, and proton density (PD) was performed in 17 patients with idiopathic cervical dystonia and 29 matched healthy control subjects. Statistical comparisons of the parametric maps between groups were conducted for various regions of interest (ROI), including major basal ganglia nuclei, the thalamus, white matter, and the cerebellum, and voxel-wise for the whole brain.
Results: Neither whole brain voxel-wise statistics nor ROI-based analyses revealed significant group differences for any qMRI parameter under investigation.
Conclusions: The negative findings of this qMRI study argue against the presence of overt microstructural tissue change in patients with idiopathic cervical dystonia. The results seem to support a common view that idiopathic cervical dystonia might primarily resemble a functional network disease.
This paper compares the production of different types of direct objects by Portuguese–German and Polish–German bilingual school-aged children in their heritage languages (HLs), Polish and European Portuguese (EP). Given that the two target languages display identical options of object realization, our main research question is whether the two HLs develop in a similar way in bilingual children. More precisely, we aim at investigating whether bilingual children acquiring Polish and EP are sensitive to accessibility and animacy when realizing a direct object in their HL. The results of a production experiment show that this is indeed the case and that the two groups of bilinguals do not differ from each other, although they may overgeneralize null objects or full noun phrases to some extent. We conclude that the bilingual acquisition of object realization is guided by the relevant properties in the target languages and is not influenced by the contact language, German.
In cells the interorganelle communication comprises vesicular and non-vesicular mechanisms. Non-vesicular material transfer predominantly takes place at regions of close organelle apposition termed membrane contact sites and is facilitated by a growing number of specialized proteins. Contacts of the endoplasmic reticulum (ER) and mitochondria are now recognized to be essential for diverse biological processes such as calcium homeostasis, phospholipid biosynthesis, apoptosis, and autophagy. In addition to these universal roles, ER-mitochondria communication serves also cell type-specific functions. In this review, we summarize the current knowledge on ER-mitochondria contacts in cells of the innate immune system, especially in macrophages. We discuss ER- mitochondria communication in the context of macrophage fatty acid metabolism linked to inflammatory and ER stress responses, its roles in apoptotic cell engulfment, activation of the inflammasome, and antiviral defense.
In this article, we hypothesize, and then demonstrate, that experiences of embarrassment have significantly increased in the United States, due in part, to the current situation in American politics under President Donald Trump. We provide support for our hypothesis by conducting both qualitative and quantitative analyses of Twitter posts in the U.S. obtained from the Crimson Hexagon database. Next, based on literature from social psychology, social neuroscience, and political theory, we propose a two-step process explaining why Trump's behavior has caused people in the U.S. to feel more embarrassment. First, compared to former representatives, Trump violates social norms in a manner that seems intentional, and second, these intentional norm violations specifically threaten the social integrity of in-group members—in this case, U.S. citizens. We discuss how these norm violations relate to the behavior of currently represented citizens and contextualize our rationale in recent changes of political representation and the public sphere. We conclude by proposing that more frequent, nation-wide experiences of embarrassment on behalf of the representative may motivate political actions to prevent further harm to individuals' self-concepts and protect social integrity.
Glioblastomas (GBs) frequently display activation of the epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR). mTOR exists as part of two multiprotein complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2). In GBs, mTORC1 inhibitors such as rapamycin have performed poorly in clinical trials, and in vitro protect GB cells from nutrient and oxygen deprivation. Next generation ATP-competitive mTOR inhibitors with affinity for both mTOR complexes have been developed, but data exploring their effects on GB metabolism are scarce. In this study, we compared the ATP-competitive mTORC1/2 inhibitors torin2, INK-128 and NVP-Bez235 to the allosteric mTORC1 inhibitor rapamycin under conditions that mimic the glioma microenvironment. In addition to inhibiting mTORC2 signaling, INK-128 and NVP-Bez235 more effectively blocked mTORC1 signaling and prompted a stronger cell growth inhibition, partly by inducing cell cycle arrest. However, under hypoxic and nutrient-poor conditions mTORC1/2 inhibitors displayed even stronger cytoprotective effects than rapamycin by reducing oxygen and glucose consumption. Thus, therapies that arrest proliferation and inhibit anabolic metabolism must be expected to improve energy homeostasis of tumor cells. These results mandate caution when treating physiologically or therapeutically induced hypoxic GBs with mTOR inhibitors.
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment contribute to all stages of tumorigenesis and are usually considered to be tumor-promoting cells. CAFs show a remarkable degree of heterogeneity, which is attributed to developmental origin or to local environmental niches, resulting in distinct CAF subsets within individual tumors. While CAF heterogeneity is frequently investigated in late-stage tumors, data on longitudinal CAF development in tumors are lacking. To this end, we used the transgenic polyoma middle T oncogene-induced mouse mammary carcinoma model and performed whole transcriptome analysis in FACS-sorted fibroblasts from early- and late-stage tumors. We observed a shift in fibroblast populations over time towards a subset previously shown to negatively correlate with patient survival, which was confirmed by multispectral immunofluorescence analysis. Moreover, we identified a transcriptomic signature distinguishing CAFs from early- and late-stage tumors. Importantly, the signature of early-stage CAFs correlated well with tumor stage and survival in human mammary carcinoma patients. A random forest analysis suggested predictive value of the complete set of differentially expressed genes between early- and late-stage CAFs on bulk tumor patient samples, supporting the clinical relevance of our findings. In conclusion, our data show transcriptome alterations in CAFs during tumorigenesis in the mammary gland, which suggest that CAFs are educated by the tumor over time to promote tumor development. Moreover, we show that murine CAF gene signatures can harbor predictive value for human cancer.
Allogeneic hematopoietic stem cell transplantation for congenital immune dysregulatory disorders
(2019)
Primary immunodeficiency disorders that predominantly affect immune regulation and mechanisms of self-tolerance have come into the limelight, because at least for a subgroup of monogenetic disorders, a targeted therapy has become available. Nevertheless, their management often involves the treatment of severely compromising, refractory, multi-organ autoimmunity, leading to further increased susceptibility to infections and complications of long-term immune suppressive treatment, including the risk of malignancy. While evidence for allogeneic hematopoietic stem cell transplantation (alloHSCT) as a curative treatment option for severely affected patients by this disease category accumulates, clear indications, and guidelines for alloHSCT are lacking. Predictive and stratification-relevant tools such as disease activity scores are largely missing and often there is not a consistent genotype-phenotype correlation within the same family to facilitate the decision whether to transplant or not. In this review, we provide a literature-based update on indications and outcomes of alloHSCT for congenital immune dysregulative inborn errors of immunity according to the IUIS classification 2017.
In seiner mit dem Otto-Hintze-Preis ausgezeichneten Habilitationsschrift bietet Markus Payk eine Entstehungsgeschichte des internationalen Rechtssystems, wie es in der Zwischenkriegszeit bestand. Demgemäß behandelt er die Pariser Vorortverträge – schwerpunktmäßig den Versailler Vertrag – von 1919/1920, mit denen ein neues zwischenstaatliches Regelungswerk erstellt wurde, das das gescheiterte System der Vorkriegszeit vor 1914 ablösen sollte. Der Autor will diese Verträge aus ihrem historischen und ideellen Kontext heraus erklären, um so deren wichtigste Charakteristika herauszuarbeiten und dabei verdeutlichen, dass ihnen "trotz aller Defizite […] [eine] einzigartige Stellung in der Geschichte der modernen Staatenbeziehungen" (S. 661) zukomme. ...
Collateral sprouting of surviving axons contributes to the synaptic reorganization after brain injury. To study this clinically relevant phenomenon, we used complex organotypic tissue cultures of mouse entorhinal cortex (EC) and hippocampus (H). Single EC-H cultures were generated to analyze associational sprouting, and double EC-H cultures were used to evaluate commissural sprouting of mossy cells in the dentate gyrus (DG) following entorhinal denervation. Entorhinal denervation (transection of the perforant path) was performed at 14 days in vitro (DIV) and associational/commissural sprouting was assessed at 28 DIV. First, associational sprouting was studied in genetically hybrid EC-H cultures of beta-actin-GFPtg and wild-type mice. Using calretinin as a marker, associational axons were found to re-innervate almost the entire entorhinal target zone. Denervation experiments performed with EC-H cultures of Thy1-YFPtg mice, in which mossy cells are YFP-positive, confirmed that the overwhelming majority of sprouting associational calretinin-positive axons are mossy cell axons. Second, we analyzed associational/commissural sprouting by combining wild-type EC-H cultures with calretinin-deficient EC-H cultures. In these cultures, only wild-type mossy cells contain calretinin, and associational and commissural mossy cell collaterals can be distinguished using calretinin as a marker. Nearly the entire DG entorhinal target zone was re-innervated by sprouting of associational and commissural mossy cell axons. Finally, viral labeling of newly formed associational/commissural axons revealed a rapid post-lesional sprouting response. These findings demonstrate extensive and rapid re-innervation of the denervated DG outer molecular layer by associational and commissural mossy cell axons, similar to what has been reported to occur in juvenile rodent DG in vivo.
Der vorliegende Band widmet sich für den Zeitraum von 1815 bis heute dem deutsch-französischen Verhältnis in 15 Einzelstudien, die entweder kulturwissenschaftlich ausgerichtet sind oder die dem Thema vor Ort in regionalen Fallbespielen nachgehen. Gemeinsame Klammer ist dabei der Rhein und dessen Anliegerregionen, womit die Herausgeber sich an neuere historische Forschungstrends anschließen. Anders als bisher wird der Rhein allerdings weder als deutschnationaler Fluss noch als natürliche französische Grenze wie vor 1945, aber auch nicht wie heute vielfach als europäisches Symbol verstanden, sondern als hybrider Raum, in dem verschiedene Akteure mit unterschiedlichen Interessen unter gegebenen Rahmenbedingungen aufeinandertrafen, was zu speziellen Prozessen und hybriden Strukturen in den jeweiligen Regionen führte. Das Ziel, die bisher dominierenden politisch motivierten Interpretationen in Frage zu stellen und die regionalen Besonderheiten und Widersprüche genauer wahrzunehmen, um die vorherrschenden nationalen und europäischen Interpretationen besser einzuordnen, erreicht der Band dabei vor allem durch die auf breiter Archivalienbasis erstellten Beiträge. ...
Background: Malaria is an increasing concern in Indonesia. Socio-demographic factors were found to strongly influence malaria prevalence. This research aimed to explore the associations between socio-demographic factors and malaria prevalence in Indonesia.
Methods: The study used a cross-sectional design and analysed relationships among the explanatory variables of malaria prevalence in five endemic provinces using multivariable logistic regression.
Results: The analysis of baseline socio-demographic data revealed the following independent risk variables related to malaria prevalence: gender, age, occupation, knowledge of the availability of healthcare services, measures taken to protect from mosquito bites, and housing condition of study participants. Multivariable analysis showed that participants who were unaware of the availability of health facilities were 4.2 times more likely to have malaria than those who were aware of the health facilities (adjusted odds ratio = 4.18; 95% CI 1.52–11.45; P = 0.005).
Conclusions: Factors that can be managed and would favour malaria elimination include a range of prevention behaviours at the individual level and using the networks at the community level of primary healthcare centres. This study suggests that improving the availability of a variety of health facilities in endemic areas, information about their services, and access to these is essential.
This paper focuses on the life and work of three of the most important men who arrived in the Philippines during the 16th century: the Augustinian Martín de Rada (1533–1578) studied at the universities of Paris and Salamanca. He was one of the best European scientists of his time in East Asia. The Dominican Domingo de Salazar (1512–1594), first bishop of Manila, studied the legitimacy of the conquest of the Philippines and wrote against the Spanish plan to conquest China. The Dominican Juan Cobo (? –1592) was the first Spanish to master the Chinese language and, through his book Shilu, the first European who introduced Christianity to the Chinese from a rational point of view and the first one to introduce European science into Chinese context. All of them were very influenced by the School of Salamanca and, from Manila, they always had their eyes on China. These three men of the late 16th century are paradigmatic examples of the influence of the University of Salamanca in the production of global knowledge in the early modernity.
Pharmakokinetik von JWH-018 und seinen Metaboliten in menschlichen Serum-, Urin- und Speichelproben
(2019)
Synthetische Cannabinoide sind seit Anfang der 2000er Jahre als Alternative zum Cannabiskonsum bekannt. Als erstes synthetisches Cannabinoid konnte JWH-018 in dem Produkt „Spice“ identifiziert werden. Aufgrund von teils behandlungspflichtigen, erheblichen Nebenwirkungen sowie von Todesfällen wurden bislang keine Probandenstudien durchgeführt.
Als erste kontrollierte Untersuchung wurde eine Pilotstudie mit sechs Probanden und sehr niedrigen Dosierungen (2 und 3 mg im Vergleich mit Placebo) mit der am besten erforschten Substanz, JWH-018, abgeschlossen. Mit der Entnahme von 14 Serum- und Speichel- sowie 5 Urinproben über einen Zeitraum von 12 Stunden nach Inhalation sollten Daten zur Pharmakokinetik und zum Metabolismus erhoben werden.
Blut, Urin und Speichel wurden nach flüssig-flüssig Extraktion mittels Flüssigchromatographie-Tandemmassenspektrometrie analysiert. Die Methoden wurden nach aktuellen Richtlinien vollständig validiert.
Serumkonzentrationen wurden zur Korrelation mit beobachteten Wirkungen bestimmt. Die maximale Serumkonzentration von JWH-018 erreichte bereits 5 min nach Inhalation 2,9-9,9 ng/ml und nahm innerhalb der nächsten 1,5 h deutlich ab, gefolgt von einem multiexponentiellen Abfall (t½ im Median 1,3 h und 5,7 h). Bei zwei Probanden lagen noch bis zu 4 Wochen nach der Applikation Spuren von JWH-018 vor. Die Konzentration des Pentansäuremetaboliten war etwas höher als die der 3-, 4- und 5-Hydroxypentylmetaboliten und des 6-Hydroxyindolmetaboliten. Bei der JWH-018 Pentansäure zeigte sich jedoch im Vergleich ein späteres Erreichen der Maximalkonzentration sowie eine deutliche Plateauphase, was sich durch enterohepatisches Cycling erklären lassen könnte.
Speicheltests dienen im forensischen wie klinischen Umfeld häufig als Schnelltest und als Indikator für anhaltende Wirkungen. Die Speichelasservierung und -lagerung erfolgte mit dem Quantisal-System. Maximale Konzentrationen von JWH-018 waren 2,2-2036 (Median 25,7) ng/ml direkt nach Inhalation und sanken in der nächsten Stunde auf nur 0,08-8,42 (Median 0,89) ng/ml, Metabolite wurden nicht nachgewiesen. Innerhalb der Eliminationsphase (mittlere Halbwertszeit 1,69 h) konnte JWH-018 während 6-12 (Median 8) h nachgewiesen werden (0,024 ng/ml Quantifizierungs-grenze). Das Konzentrationsverhältnis von Speichel zu Serum variierte intra- und interindividuell stark in einem Bereich von 0,05-555 (Median 1,38) ng/ml, was eine Extrapolation der Speichelkonzentrationen auf Serum/Plasma ausschließt.
Urin wurde zu mindestens 5 Zeitpunkten entnommen und sowohl mit, als auch ohne β Glukuronidasebehandlung analysiert. Die Muttersubstanz war nicht nachweisbar, dafür 13 ihrer Metaboliten, die alle hochgradig konjugiert vorlagen. Die Konzentrationen des vorherrschenden Metaboliten, JWH-018 Pentansäure, lagen unter 5 ng/ml, wurden aber bei zwei Probanden noch bis zu 4 Wochen nach der Einnahme nachgewiesen. Die JWH-073 Butansäure wurde in die Urinanalyse miteinbezogen, da es Hinweise auf eine metabolische Bildung gab. Die Untersuchungsergebnisse können klar belegen, dass die Butansäure als Metabolit nach Konsum von JWH-018 entsteht. Wie im Serum wurden die Metabolite 3-, 4- und 5-Hydroxypentyl- sowie 6-Hydroxyindol-JWH-018 nachgewiesen. Zusätzlich zeigten sich aber auch geringe Signale von 4-, 5- und 7 Hydroxyindol- sowie von 2-Hydroxypentyl-JWH-018 und ein Signal neben dem 3 Hydroxypentylmetaboliten, welches ein weiteres hydroxyliertes Isomer repräsentieren dürfte. Weiterhin zeigten sich wie bereits im Serum auch in allen Urinproben bis zu zwei Messsignale mit den gleichen Fragmenten wie die JWH-018 Pentansäure. In Anlehnung an eine in-vitro Metabolismusstudie ist davon auszugehen, dass es sich um dihydroxylierte und dehydrierte Isomere von JWH-018 handelt, die als Hydroxy-Keto-Metabolite postuliert wurden. Im Allgemeinen lagen hydroxylierte Metaboliten bereits 10 h nach der Inhalation in Konzentrationen von weniger als 1 ng/ml vor. Die unterschiedliche Ausscheidung von Carbonsäuren und hydroxylierten Metaboliten kann bei der Einordnung des Konsumzeitpunkts helfen. Alle Konzentrationen lagen deutlich niedriger als für Urinproben von authentischen JWH-018 Konsumenten beschrieben.
Bei der Auswertung der Messdaten in Bezug auf die 2 mg und die 3 mg Dosis ließen sich keine signifikanten Unterschiede nachweisen, was sich nach Untersuchung der nicht inhalierten Restmengen durch erhebliche Schwankungen in der Applikation erklären lässt.
Die Daten sprechen für eine ausgeprägte Mehrkompartimentkinetik und eine langsame terminale Eliminierung von JWH-018 und allen Metaboliten, was zu einer Akkumulation bei chronischen Konsumenten führen kann. Dies ähnelt den Erfahrungen mit dem Cannabiswirkstoff Tetrahydrocannabinol (THC) und legt langanhaltende Effekte und eine Toleranzentwicklung nahe.
High-energetic heavy-ion collisions offer the unique opportunity to produce and to study dense nuclear matter in the laboratory. The future Facility for Antiproton and Ion Research (FAIR) in Darmstadt, Germany, will provide beams of heavy nuclei up to kinetic energies of 11 GeV/nucleon. At these energies, the nuclear matter in the collision zone of two nuclei will be compressed to densities of up to 5 − 10 times the saturation density of atomic nuclei, similar to matter densities existing in the core of massive neutron stars. Under those conditions, nucleons are expected to melt and form a new state of matter, which consists of quarks and gluons, the so called Quark-Gluon Plasma (QGP). The search for such a phase transition from hadronic to partonic matter, and the exploration of the nuclear matter equation-of-state at high densities are the major goals of heavy ion experiments worldwide.
The observables, which are proposed to probe the properties of dense nuclear matter and possible phase transitions, include multi-strange hyperons, antibaryons, lepton pairs, collective flow of identified particles, fluctuations and correlations of various particles, particles containing charm quarks, and hypernuclei. These observables have to be measured in multi-dimensions, i.e. as function of collision centrality, rapidity, transverse momentum, energy, emission angle, etc., which requires extremely high statistics. Moreover, some of these particles are produced very rarely.
Therefore, the Compressed Baryonic Matter (CBM) experiment at FAIR is designed to run at collision rates of up to 10 MHz, in order to perform measurements with unprecedented precision. Due to the complicated decay topology of many observables, no hardware trigger can be applied, and the data have to be analysed online in order to filter out the interesting events.
This strategy requires free-streaming read-out electronics, which provides time stamps to all detector signals, a high performance computer center, and high-speed reconstruction algorithms, which provide an online track and event reconstruction based on time and position information of the detector hits (”4-D“ reconstruction).
The core detector of the CBM experiment is the Silicon Tracking System (STS). The main task of the STS is to provide track reconstruction and momentum de- termination of charged particles originating from beam-target interactions. To fulfil the whole tasks the STS is located in the large gap of a superconducting dipole magnet with a bending power of 1 Tm providing momentum measurements for charged particles. The STS comprises 8 detector stations, which are positioned from 30 cm to 100 cm downstream the target. The corresponding active area of the stations grows up from 40×50 cm 2 up to 100×100 cm 2 with a totalarea of 4 m2. The silicon double-sided sensors exhibit 1024 strips on each side with a stereo angle at p-side of 7.5 ◦ and a strip pitch of 58 μm. The strip length ranges from 2 cm for sensors located in a close vicinity to the beam axis, up to 12 cm for other sensors where the flux of the reaction products drops down substantially. In total, the STS consist of 896 sensors mounted on 106 detector ladders. The detector readout electronics dissipates 40 kW and will be equipped with a CO 2 bi-phase cooling system. The detector including electronics will be mounted in a thermal enclosure to allow for sensor operation at below −5 ◦ C which minimizes radiation induced leakage currents.
The task of the STS is to measure the trajectories of up to 800 charged particles per collision with an efficiency of more than 95% and a momentum resolution of 1 − 2%. In order to guarantee the required performance over the full lifetime of the CBM experiment, the detector system has to have a low material budget, a high granularity, a high signal-to-noise (SNR) ratio, and a high radiation tolerance. As a result of optimisation studies, the STS consists of double-sided silicon microstrip sensors, about 300 μm thick, which have to provide a SNR ratio of more than 10, even after radiation with the expected equivalent lifetime fluence of 10 14 1 MeV n eq cm −2.
This thesis is devoted to the characterization of double-sided silicon microstrip sensors with an emphasis on investigation of their radiation hardness. Different prototypes of double sided silicon sensors produced by two vendors have been irradiated by 23 MeV protons up to the double life time fluence for the CBM experiment (2 × 10 14 1 MeV n eq cm −2 ).
The sensor properties have been characterised before and after irradiation. It was found, that after irradiation with a double lifetime fluence the leakage current increased 1000 times, which results in an increased shot noise. Moreover, the relative charge collection efficiency of irradiated with respect to non-irradiated sensors drops down to 85% for the lifetime equivalent fluence, and down to 73% for the double lifetime fluence, both for the p-side and n-side. For non-irradiated sensors the SNR was found to be in the range of 20 − 25, whereas for irradiated sensors it dropped down to 12 − 17.
In addition to the sensor characterization, a part of this thesis was devoted to the optimisation of the sensor readout scheme. In order to investigate the possible increase of SNR, and to reduce the number of readout channels in the outer aperture of STS, three versions of routing lines have been realized for the p-side readout of the sensor prototype, and have been tested in the laboratory and under beam conditions.
The tests have been performed with different inclination angles between beam direction and sensor surface, corresponding to the polar angle acceptance of the CBM experiment, which is from 2.5 ◦ to 25 ◦.
As a result of the studies carried out in this thesis work, the radiation hardness of the double-sided silicon microstrip sensors developed for the CBM STS detector was confirmed. Also the advantage of individual read-out of sensor channels in the lateral regions of the detector was verified. This allowed to start the tendering process for sensor series production in industry, an important step towards the construction of the detector in the coming years.
Cardiovascular diseases are a leading cause of morbidity and mortality worldwide. Aging inflicts structural and molecular changes on the heart that oftentimes involve ischemic events, cardiomyocyte apoptosis and cardiac stiffening, which makes it a major risk factor for cardiovascular disease. After being disregarded as transcriptional noise for a long time, long non-coding RNAs have lately emerged as key regulators of many cellular processes in physiology and disease of virtually all tissues and organs, with some of them being differentially regulated during aging.
This study identified a long non-coding transcript antisense to the OXCT1 gene locus, Sarrah, to be downregulated in the heart during aging, after acute myocardial infarction and upon heart failure with preserved ejection fraction. Sarrah is expressed in several cardiac cell types with highest levels in cardiomyocytes, where it is predominantly localized in the nucleus. In mouse and human cardiomyocytes, Sarrah levels are reduced upon exposure to hypoxia or treatment with hypoxiamimetic agents in vitro.
Sarrah exerts an anti-apoptotic function in mouse and human cardiomyocytes as assessed from caspase activity and annexin V staining. Histological stainings of Sarrah-depleted human engineered heart tissue organoids and Sarrah overexpressing infarcted mouse hearts confirmed its anti-apoptotic function. Sarrah also plays a role in cardiomyocyte contractility, which is substantially impaired upon Sarrah silencing in human engineered heart tissue and neonatal rat cardiomyocytes. Additionally, cardiomyocytal Sarrah stimulates endothelial cell proliferation via paracrine effects as observed after Sarrah overexpression in mouse hearts as well as in co-culture settings with human endothelial cells and Sarrah-depleted or Sarrah overexpressing human cardiomyocytes. A microarray analysis revealed that silencing Sarrah in human cardiomyocytes induced apoptosisrelated gene expression. Mechanistically, Sarrah was predicted to form triplexes in human and mouse with promoters of genes downregulated, but not upregulated after Sarrah knockdown, suggesting that Sarrah interacts with target genes to activate their transcription. This interaction was confirmed in vitro using nucleic acid oligonucleotides containing the sequences of the Sarrah triplex motif and the Sarrah binding site of the exemplary target gene GPC6 of both human and mouse. RNA immunoprecipitation experiments in human cells demonstrated that Sarrah is associated with open chromatin, transcription factor CRIP2, transcriptional co-activator p300 and DNA-RNA hybrid structures that also occur in Sarrah target gene promoters, which indicated that Sarrah activates gene expression by triplex formation and recruitment of protein interaction partners. Deleting the triplex motif of endogenous Sarrah in mouse cardiomyocytes augmented apoptosis, showing that triplex formation is of functional relevance for Sarrah action.
Finally, overexpressing Sarrah in an acute myocardial infarction mouse model improved recovery of cardiac contractile function as assessed from ejection fraction, stroke volume, wall motion and wall thickness measured by echocardiography and magnetic resonance imaging. Infarct size was substantially reduced in Sarrah overexpressing mice compared with controls. This in vivo study implies that restoring Sarrah levels in the aged or infarcted heart bears significant therapeutic potential, which can be attributed to the combination of three Sarrah effects: increased cardiomyocytes survival, enhanced contractility of individual cardiomyocytes and paracrine stimulation of endothelial cell proliferation likely contributing to increased angiogenesis and tissue perfusion.
In summary, cardiac lncRNA Sarrah is evolutionary conserved with regard to its genomic locus, function and molecular mechanism. Via triplex formation with gene promoters, it is capable to activate a set of target genes that together mediate the anti-apoptotic and pro-contractile function of Sarrah in cardiomyocytes and that confer angiogenic effects to endothelial cells. A therapeutic utilization of Sarrah in the context of myocardial ischemia is conceivable in the future if Sarrah upregulation proves to be beneficial in further studies.
Two byzantine churches in Constantinople - a photographic, historical and bibliographical context
(2019)
Background: Developmental biology relies to a large extent on the observation and comparison of phenotypic traits through time using high resolution microscopes. In this context, transparent model organisms such as the zebrafish Danio rerio in which developing tissues and organs can be easily observed and imaged using fluorescent proteins have become very popular. One limiting factor however is the acquisition of a sufficient amount of data, in standardized and reproducible conditions, to allow robust quantitative analysis. One way to improve this is by developing mounting methods to increase the number of embryos that can be imaged simultaneously in near-to-identical orientation.
Results: Here we present an improved mounting method allowing semi-automated and high-content imaging of zebrafish embryos. It is based on a 3D-printed stamp which is used to create a 2D coordinate system of multiple μ-wells in an agarose cast. Each μ-well models a negative of the average zebrafish embryo morphology between 22 and 96 h-post-fertilization. Due to this standardized and reproducible arrangement, it is possible to define a custom well plate in the respective imaging software that allows for a semi-automated imaging process. Furthermore, the improvement in Z-orientation significantly reduces post-processing and improves comparability of volumetric data while reducing light exposure and thus photo-bleaching and photo-toxicity, and improving signal-to-noise ratio (SNR).
Conclusions: We present here a new method that allows to standardize and improve mounting and imaging of embryos. The 3D-printed stamp creates a 2D coordinate system of μ-wells in an agarose cast thus standardizing specimen mounting and allowing high-content imaging of up to 44 live or mounted zebrafish embryos simultaneously in a semi-automated, well-plate like manner on inverted confocal microscopes. In summary, image data quality and acquisition efficiency (amount of data per time) are significantly improved. The latter might also be crucial when using the services of a microscopy facility.
Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, but early microbiological diagnosis is difficult. As data on the value of biomarkers in the CNS are scarce, in particular in children, we retrospectively analyzed the performance of galactomannan (GM) and PCR assays in CNS samples of 15 children with proven and probable CNS IMD and of 32 immunocompromised children without fungal infection. Galactomannan in the cerebrospinal fluid (CSF) was assessed in nine of the 15 pediatric patients and was positive in five of them. Polymerase chain reaction (PCR) was performed in eight of the 15 patients and detected nucleic acids from molds in six patients. Galactomannan and PCR in CNS samples were the only positive microbiologic parameter in the CNS in three and two patients, respectively. In four patients, PCR specified the pathogen detected in microscopy. Galactomannan and PCR results remained negative in the CSF of all immunocompromised children without evidence for CNS IMD. Our data suggest that GM and PCR in CNS specimens are valuable additional tools in diagnosing CNS IMD and should be included in the work up of all pediatric patients with suspected mold disease of the CNS.
Nein, hier sollte keine Gesamtwürdigung von Person und Werk des Pierre d’Ailly vorgenommen oder dessen Epoche im Spiegel seiner Person unter vorwaltend kirchlich-politischen Aspekten analysiert werden, zumal darüber schon in jüngerer und jüngster Zeit Studien von Bernard Guenée sowie von Hélène Millet und Monique Maillard-Luypaert handelten. Vielmehr galt es auf der Pariser Tagung im März 2017, deren – sorgfältig redigierte, u. a. mit Auswahlbibliografie, Handschriftenverzeichnis, Personenregister und Zusammenfassungen der Beiträge in Französisch und Englisch versehene – Akten hier anzuzeigen sind, die vielfältigen Aspekte und Facetten der aktiven und schriftstellerischen Tätigkeit eines Mannes zu untersuchen, den man als "esprit universel" und "intellectuel engagé" charakterisieren mag, wie es Jacques Verger, Mitherausgeber und Mitglied der das Kolloquium in der Hauptsache tragenden Académie des Inscriptions et Belles-Lettres, einleitend tut (S. 10f.). ...
Background: Individuals afflicted with nonspecific chronic low back pain (CLBP) exhibit altered fundamental movement patterns. However, there is a lack of validated analysis tools. The present study aimed to elucidate the measurement properties of a functional movement analysis (FMA) in patients with CLBP.
Methods: In this validation (cross-sectional) study, patients with CLPB completed the FMA. The FMA consists of 11 standardised motor tasks mimicking activities of daily living. Four investigators (two experts and two novices) evaluated each item using an ordinal scale (0–5 points, one live and three video ratings). Interrater reliability was computed for the total score (maximum 55 points) using intra class correlation and for the individual items using Cohen’s weighted Kappa and free-marginal Kappa. Validity was estimated by calculating Spearman’s Rho correlations to compare the results of the movement analysis and the participants’ self-reported disability, and fear of movement.
Results: Twenty-one participants (12 females, 9 males; 42.7 ± 14.3 years) were included. The reliability analysis for the sum score yielded ICC values between .92 and.94 (p < .05). The classification of individual scores are categorised "slight" to "almost perfect" agreement (.10–.91). No significant associations between disability or fear of movement with the overall score were found (p > .05). The study population showed comparably low pain levels, low scores of kinesiophobia and disability.
Conclusion: The functional movement analysis displays excellent reliability for both, live and video rating. Due to the low levels of disability and pain in the present sample, further research is necessary to conclusively judge validity.
Background. Tracheal intubation still represents the "gold standard" in securing the airway of unconscious patients in the prehospital setting. Especially in cases of restricted access to the patient, video laryngoscopy became more and more relevant.
Objectives. The aim of the study was to evaluate the performance and intubation success of four different video laryngoscopes, one optical laryngoscope, and a Macintosh blade while intubating from two different positions in a mannequin trial with difficult access to the patient.
Methods. A mannequin with a cervical collar was placed on the driver’s seat. Intubation was performed with six different laryngoscopes either through the driver’s window or from the backseat. Success, C/L score, time to best view (TTBV), time to intubation (TTI), and number of attempts were measured. All participants were asked to rate their favored device.
Results. Forty-two physicians participated. 100% of all intubations performed from the backseat were successful. Intubation success through the driver’s window was less successful. Only with the Airtraq® optical laryngoscope, 100% success was achieved. Best visualization (window C/L 2a; backseat C/L 2a) and shortest TTBV (window 4.7 s; backseat 4.1 s) were obtained when using the D-Blade video laryngoscope, but this was not associated with a higher success through the driver’s window. Fastest TTI was achieved through the window (14.2 s) when using the C-MAC video laryngoscope and from the backseat (7.3 s) when using a Macintosh blade.
Conclusions. Video laryngoscopy revealed better results in visualization but was not associated with a higher success. Success depended on the approach and familiarity with the device. We believe that video laryngoscopy is suitable for securing airways in trapped accident victims. The decision for an optimal device is complicated and should be based upon experience and regular training with the device.
Representation is a process of making, accepting, or rejecting representative claims (Disch, 2015; Saward, 2014). This groundbreaking insight challenged the standard assumption that representative democracy can be reduced to elections and activities of elected representatives (Pitkin, 1967). It broadened the scope of representative democracy to encompass representation activities beyond those authorized by elections, transformed our thinking and provided a new perspective, putting claims and their reception into the center. This paradigm shift erased the distinction between elected and non-elected representatives and disclosed the potential of non-elected actors’ claims to represent (Andeweg, 2003; Kuyper, 2016; Rosanvallon & Goldhammer, 2008; Saward, 2006, 2009; Van Biezen & Saward, 2008). In spite of this lively debate, we identify an important gap in the literature: while this paradigmatic shift inspired many authors, conceptual frameworks that can be applied for systematic empirical analysis of real-life cases are missing. In this article, we fill this gap and propose frameworks for assessing and validating a variety of real-life claims. Our study provides empirical substance to the ongoing theoretical debates, helping to translate the mainly theoretical ‘claim approach’ into empirical research tools. It helps to transform the conventional wisdom about what representation can (not) be and shines a new light on the potential future of (claims on) representation.
The system of representative democracy is under considerable strain. Its institutions are struggling to maintain legitimacy, and its elected representatives are failing to keep their monopoly on (formal) political representation. An emerging multitude of (new) claim makers contests the authority of elected representatives as well as the functioning of the existing system of representative democracy by alleging misrepresentation. In this article, we identify a significant shortcoming in Saward’s claims-making approach; specifically, we argue that it offers little direction in addressing misrepresentation. We distinguish between claims of representation and claims of misrepresentation, and show how the latter can fulfill one, two or all three of the following functions: (1) they appeal to an enemy/antagonist (strategy), (2) identify causes of misrepresentation related to policies, politics, and polity (persuasion), and (3) claim to create a new linkage to "the people", sometimes present themselves as new representatives (reframing). To test this proposed framework, we compare claims of misrepresentation in Brazil made by civil society groups (before and during the presidential impeachment between 2014 and 2016) and in Germany (focusing on the parliamentarians of the Alternative for Germany during the first six months of mandate). Our results suggest that claims of misrepresentation are not intrinsically democratic or undemocratic, but are instead ambiguous, have different manifestations and disparate impacts on the representative system. Our article contributes to the conceptual development of the claims approach and to further understanding several critical and current challenges to representative democracy.
The established notion of political representation is challenged on multiple accounts—theoretically, conceptually, and empirically. The contributions to this thematic issue explore the constructivist turn as the means for rethinking political representation today around the world. The articles included here seek to reconsider representation by theoretically and empirically reassessing how representation is conceptualized, claimed and performed—in Western and non-Western contexts. In recognition that democratic representation in Western countries is in a process of fundamental transformation and that non-Western countries no longer aim at replicating established Western models, we look for representation around the world—specifically in: Belgium, Brazil, France, Germany, China, and India. This enables us to advance the study of representative democracy from a global perspective. We show the limits and gaps in the constructivist literature and the benefits of theory-driven empirical research. Finally, we provide conceptual tools and frameworks for the (comparative) study of claims of representation.
Relying on the theory of Saward (2010) and Disch (2015), we study political representation through the lens of representative claim-making. We identify a gap between the theoretical concept of claim-making and the empirical (quantitative) assessment of representative claims made in the real world’s representative contexts. Therefore, we develop a new approach to map and quantify representative claims in order to subsequently measure the reception and validation of the claims by the audience. To test our method, we analyse all the debates of the German parliament concerned with the introduction of the gender quota in German supervisory boards from 2013 to 2017 in a two-step process. At first, we assess which constituencies the MPs claim to represent and how they justify their stance. Drawing on multiple correspondence analysis, we identify different claim patterns. Second, making use of natural language processing techniques and logistic regression on social media data, we measure if and how the asserted claims in the parliamentary debates are received and validated by the respective audience. We come to the conclusion that the constituency as ultimate judge of legitimacy has not been comprehensively conceptualized yet.