1,824 research outputs found
Schema unification and morphological productivity: A diachronic perspective
Unified schemas which allow for deriving multiply complex word-formation products are a central concept in Construction Morphology (CxM). Based on examples such as un-V-able formations in English, Booij (2007: 38) argues that unified schemas (in this case: [un[Vable] A]A) can be conceived of as âshort cuts in coining new complex wordsâ. In this paper, we explore three prospective cases of schema unification and discuss what kind of evidence supports the assumption of unified schemas. The first two case studies are diachronic in nature. Drawing on corpus analyses of data from the Early New High German period (1350â1650) and from the early stages of New High German, we show how the developments of the complex patterns diverge from the developments of their counterparts. To this end, we analyze the frequency and productivity of the (sub-)constructions and assess the semantics of the word-formation products. Firstly, nominalization with the suffix -ung has been shown to undergo a diachronic decrease in morphological productivity (Demske 2000; Hartmann 2016). However, unified schemas such as [Be-X-ung]N or [(PREF)-X-ierung]N are shown to be still productive, e.g. Beplankung, Belaberung, Vercomedianisierung (from www.wortwarte.de, a collection of neologisms). In a similar vein, complex derivation of the type [un-V-lich]ADJ âun-V-ableâ is shown to have remained productive for a longer period of time than its simplex parent schema [un-V-lich]ADJ. Moreover, many un-V-lich derivatives historically precede their unprefixed counterparts, or lack them altogether (unwiderstehlich âirresistibleâ, but *widerstehlich). Our third case study explores present day German pseudoparticiples (bebrillt âbespectacledâ) using web data. The complex pattern can be shown to diverge stylistically from its parents schemas and also to provide semantically more uniform derivatives. Overall, our results show that the concept of unified schemas can help explain important differences in the development of the individual subpatterns in terms of morphological productivity and in terms of semantic aspects of the word-formation constructions
Validierung der Herstellung und QualitĂ€tsprĂŒfung autologer dendritischer Zellen fĂŒr die adjuvante Immuntherapie
Am Institut fĂŒr Klinische HĂ€mostaseologie und Transfusionsmedizin der UniversitĂ€t des Saarlandes wurde 2012 ein Forschungsprojekt initiiert, um die Herstellungserlaubnis fĂŒr dendritische Zellen zur adjuvanten Immuntherapie von höhergradigen Gliomen zu erlangen.
Gliome sind die hĂ€ufigsten primĂ€ren Hirntumore, wobei die höhergradig-malignen Glioblastome unter diesen den gröĂten Anteil ausmachen. Die Standardtherapie dieser TumorentitĂ€t ist die Kombination aus Operation und Radiochemotherapie. Unter dieser Therapie liegt die mittlere Ăberlebenszeit der Patienten bei 14,6 Monaten. Auf Grund der nicht zufriedenstellenden Therapieergebnisse beschĂ€ftigen sich viele Studien mit alternativen Therapiemöglichkeiten, unter anderem auch mit Arzneimitteln fĂŒr neuartige Therapien. Zu diesen zĂ€hlen auch somatische Zelltherapeutika, wie beispielsweise dendritische Zellen zur adjuvanten Immuntherapie.
Um somatische Zelltherapeutika zur Anwendung am Patienten herstellen zu dĂŒrfen, muss dem herstellenden Labor durch die zustĂ€ndige Landesaufsichtsbehörde eine Herstellungserlaubnis erteilt werden. Diese Herstellungserlaubnis wird beim saarlĂ€ndischen Ministerium fĂŒr Soziales, Gesundheit, Frauen und Familie beantragt und durch dieses erteilt. Zuvor mĂŒssen zahlreiche Verfahrensschritte im Herstellungsprozess etabliert sowie validiert werden und Funktionstests mit den generierten dendritischen Zellen durchgefĂŒhrt werden. Alle hierbei gewonnenen Ergebnisse werden in Form eines Validierungsberichtes der zustĂ€ndigen Behörde vorgelegt.
Ziel dieser Arbeit war es, durch die Etablierung und Validierung unterschiedlicher Methoden zur Erlangung der Herstellungserlaubnis beizutragen. Hierzu wurden verschiedenste Untersuchungen an Proben der DZ-Kulturen durchgefĂŒhrt, die sowohl Sicherheit als auch QualitĂ€t des Herstellungsprozesses und des zellulĂ€ren Produktes gewĂ€hrleisten sollen.In 2012 the Institute for Clinical Hemostaseology and Transfusion Medicine of the University of the Saarland started a research project to obtain the permission for the manufacturing of dendritic cells for adjuvant immunotherapy of malignant glioma.
Gliomas are the most frequent primary brain tumors and the high-grade glioblastomas account for the largest part of these. The standard course of therapy for high-grade glioblastoma is the combination of operation, radio- and chemotherapy. Under this therapy the mean survival time for a patient amounts to 14,6 month. Due to these poor treatment outcomes, many studies are concerned with alternative therapy approaches for this tumor entity, as for example with Advanced Therapy Medical Products. These also include somatic cell based therapeutics, such as dendritic cells for adjuvant immunotherapy.
To be authorized to produce somatic cell based therapeutics for human use the producer has to obtain the permission of manufacturing. This permission is applied at the Ministry for Social Affairs, Health Care, Women and Family of the Saarland. To obtain this permission, numerous procedural steps have to be proved as well as established and performance tests have to be carried out with the manufactured dendritic cells. All results gained at this were submitted to the competent authority in form of a validation report.
The object of this research was to contribute to the obtainment of permission for the manufacturing by validation and establishment of different methods. For this purpose different investigations on the dendritic cells were carried out to prove quality and safety of the manufacturing process as well as the manufactured product
Elucidating different pattern of immunoregulation in BALB/c and C57BL/6 mice and their F1 progeny
© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the articleâs Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the articleâs Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ .Helminths are large multicellular parasites that infect one quarter of the human population. To prolong their survival, helminths suppress the immune responses of their hosts. Strongyloides ratti delays its expulsion from the gut by induction of regulatory circuits in a mouse strain-specific manner: depletion of Foxp3+ regulatory T cells (Treg) improves the anti-S. ratti immunity in BALB/c but not in C57BL/6 mice. In the current study we compare the hierarchy of immunoregulatory pathways in BALB/c, C57BL/6 mice and their F1 progeny (BALB/c Ă C57BL/6). Using multicolor flow cytometry, we show that S. ratti induces a distinct pattern of inhibitory checkpoint receptors by Foxp3+ Treg and Foxp3- T cells. Intensity of expression was highest in C57BL/6 and lowest in BALB/c mice, while the F1 cross had an intermediate phenotype or resembled BALB/c mice. Treg subsets expanded during infection in all three mouse strains. Similar to BALB/c mice, depletion of Treg reduced intestinal parasite burden and increased mucosal mast cell activation in S. ratti-infected F1 mice. Our data indicate that Treg dominate the regulation of immune responses in BALB/c and F1 mice, while multiple regulatory layers exist in C57BL/6 mice that may compensate for the absence of Treg.Open Access funding enabled and organized by Projekt DEAL.info:eu-repo/semantics/publishedVersio
A quantitative synthesis study on body mass index and associated factors among adult men and women in Switzerland
Excess weight is caused by multiple factors and has increased sharply in Switzerland since the 1990s. Its consequences represent a major challenge for Switzerland, both in terms of health and the economy. Until now, there has been no cross-dataset overview study on excess weight in adults in Switzerland. Therefore, our aim was to conduct the first synthesis on excess weight in Switzerland. We included all existing nationwide Swiss studies (eight total), which included information on body mass index (BMI). Mixed multinomial logistic regression analyses were performed to assess the associations between different socio-demographic, lifestyle cofactors and the World Health Organization (WHO) categories for BMI. Along with lifestyle factors, socio-demographic factors were among the strongest determinants of BMI. In addition, self-rated health status was significantly lower for underweight, pre-obese and obese men and women than for normal weight persons. The present study is the first to synthesise all nationwide evidence on the importance of several socio-demographic and lifestyle factors as risk factors for excess weight. In particular, the highlighted importance of lifestyle factors for excess weight opens up the opportunity for further public health interventions
Handreichung Anrechnung Teil 1. Ein theoretischer Ăberblick
Diese Handreichung gibt in neun Kapiteln einen theoretischen Einblick in das Thema Anrechnung. Dabei werden u. a. Anrechnungsverfahren, zentrale Konzepte und Bezugsrahmen sowie die QualitĂ€tssicherung in Anrechnungsprozessen in den Blick genommen. Die Handreichung wird ergĂ€nzt durch einen zweiten Teil, der Praxiserfahrungen mit Anrechnung einbezieht. Diese Publikation ist im Rahmen der wissenschaftlichen Begleitung des Bund-LĂ€nder-Wettbewerbs âAufstieg durch Bildung: offene Hochschulenâ entstanden. (Hrgs.
Structural and mechanistic aspects influencing the ADAM10-mediated shedding of the prion protein
Background: Proteolytic processing of the prion protein (PrPC) by endogenous proteases generates bioactive membrane-bound and soluble fragments which may help to explain the pleiotropic roles of this protein in the nervous system and in brain diseases. Shedding of almost full-length PrPC into the extracellular space by the metalloprotease ADAM10 is of peculiar relevance since soluble PrP stimulates axonal outgrowth and is protective in neurodegenerative conditions such as Alzheimerâs and prion disease. However, molecular determinates and mechanisms regulating the shedding of PrP are entirely unknown.
Methods: We produced an antibody recognizing the neo-epitope of shed PrP generated by ADAM10 in biological samples and used it to study structural and mechanistic aspects affecting the shedding. For this, we investigated genetically modified cellular and murine models by biochemical and morphological approaches.
Results: We show that the novel antibody specifically detects shed PrP in cell culture supernatants and murine brain. We demonstrate that ADAM10 is the exclusive sheddase of PrPC in the nervous system and reveal that the glycosylation state and type of membrane-anchorage of PrPC severely affect its shedding. Furthermore, we provide evidence that PrP shedding can be modulated by pharmacological inhibition and stimulation and present data suggesting that shedding is a relevant part of a compensatory network ensuring PrPC homeostasis of the cell.
Conclusions: With the new antibody, our study introduces a new tool to reliably investigate PrP-shedding. In addition, this study provides novel and important insight into the regulation of this cleavage event, which is likely to be relevant for diagnostic and therapeutic approaches even beyond neurodegeneration
Belagerte Moderne: Krieg und Kommune in der französischen Druckgraphik 1870/71 ; Begleitheft zur Ausstellung
Der Deutsch-Französische Krieg und die gewaltsamen Auseinandersetzungen um die Pariser Kommune stellen einen denkbar scharfen Kontrast zum kulturellen Leben der modernen Metropole Paris in den Jahren vor 1870 dar. Die 1860er Jahre waren auch in den bildenden KĂŒnsten von einem produktiven Aufbruch gekennzeichnet: Ădouard Manet hatte mit ersten Skandalen in Ausstellungen auf sich aufmerksam gemacht; Maler wie Claude Monet und Camille Pissarro begannen damit, den Impressionismus herauszubilden; und eine Reihe von ambitionierten Druckgraphikern hatte die Radierung als anspruchsvolles und durchaus modernes Bildmedium wiederbelebt. WĂ€hrend Krieg und Kommune in der offiziellen Kunst und im Impressionismus vergleichsweise wenige Spuren hinterlassen haben, lassen sich die einschneidenden Ereignisse der Jahre 1870 und 1871 in der Druckgraphik gut nachvollziehen. Radierungen von Adolphe Martial PotĂ©mont, Maxime Lalanne oder François Pierdon fĂŒhren vor Augen, wie die KĂŒnstler mit ihren zuvor entwickelten kĂŒnstlerischen Mitteln auf die radikal verĂ€nderte Situation zu reagieren versuchten. Ausstellung und Begleitheft stellen ausgewĂ€hlte Druckgraphiken von französischen KĂŒnstlern ins Zentrum, um einen etwas anderen Blick auf den Deutsch-Französischen Krieg und die Kommune zu richten
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