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A thylakoid membrane preparation isolated from the blue-green alga Anacystis nidulans was freed from carboxysomes, soluble enzymes and the pigment P750 by floating in a discontinuous sucrose density gradient. In a buffer containing sucrose and the zwitterionic detergent Miranol S2M-SF the thylakoids were loaded on a linear 10-18% sucrose density gradient which also contained Miranol. The sedimentation yielded three bands, the lower two of which were green and the upper one was orange. The light green band in the middle of the gradient was the only one to show any photosystem II activity. This was measured as light-induced electron transport from diphenylcarbazide (DPC) to dichlorophenol-indophenol (DCPIP). The activity was sensitive to dichlorophenyl-dimethylurea (DCMU).
The red absorption maximum of the particles in this middle band - henceforth called photosystem II particles - was found at 672 nm and the maximum of their low temperature fluorescence emission spectrum at 685 nm upon excitation with blue light. Cytochrome b559 was the only cytochrome found in these particles; it was present at an average ratio of one molecule cytochrome per 40 -50 molecules chlorophyll a. C550 photoreduction with accompanying photooxidation of cytochrome b559 was also observed in the photosystem II particles. Good photosystem II preparations did not contain any detectable amounts of P 700.
By means of sodium dodecylsulfate polyacrylamide gel electrophoresis the polypeptide composition of the photosystem II particles was studied. Dissolution of the chlorophyll protein complexes was done under strongly denaturing conditions; consequently, no green bands were observed on the gels. The polypeptide pattern of the photosystem II particles showed two strong predominant bands of protein components with apparent molecular weights (app. mol. wts.) of about 50 000 and 48 000. These two bands are unique for photosystem II. Two other weaker bands were also found characteristic for photosystem II, the band of a polypeptide with an app. mol. wt. of 38 000 and that of a polypeptide with an app. mol. wt. of 31 000. Sometimes in addition the weak band of a polypeptide with the app. mol. wt. 27 000 was observed on the gel. The polypeptide 38 000 aggregated upon boiling of the sample in the presence of the denaturing agents prior to the electrophoresis, yielding an aggregate with an app. mol. wt. of 50 000. Additional polypeptides which were often found in the photosystem II particle preparation could be identified as subunits of the coupling factor of photophosphorylation CF1. None of the polypeptides described as characteristic for photosystem II are due to proteolytic activity.
As the observed photosystem II activity was found to be DCMU-sensitive it appears that the DCMU-binding protein is among the here described photosystem II polypeptides. Moreover, the authors have reason to believe that one of the major protein components found characteristic for photosystem II is cytochrome b559.
We characterize optimal redistribution in a dynastic family model with human capital. We show how a government can improve the trade-off between equality and incentives by changing the amount of observable human capital. We provide an intuitive decomposition for the wedge between human-capital investment in the laissez faire and the social optimum. This wedge differs from the wedge for bequests because human capital carries risk: its returns depend on the non-diversi
able risk of children's ability. Thus, human capital investment is encouraged more than bequests in the social optimum if human capital is a bad hedge for consumption risk.
We present empirical evidence on the heterogeneity in monetary policy transmission across countries with different home ownership rates. We use household-level data together with shocks to the policy rate identified from high-frequency data. We find that housing tenure reacts more strongly to unexpected changes in the policy rate in Germany and Switzerland –the OECD countries with the lowest home ownership rates– compared with existing evidence for the U.S. An unexpected decrease in the policy rate by 25 basis points increases the home ownership rate by 0.8 percentage points in Germany and by 0.6 percentage points in Switzerland. The response of non-housing consumption in Switzerland is less heterogeneous across renters and mortgagors, and has a different pattern across age groups than in the U.S. We discuss economic explanations for these findings and implications for monetary policy.
In der vorliegenden Arbeit wurde erstmals die Interaktion von A. baumannii mit humanem Plasminogen untersucht. Mit dem Translations-Elongationsfaktor TufAb, dem äußeren Membranprotein OmpW sowie dem Lipoprotein p41 konnten insgesamt drei Plasminogen-bindende Proteine von A. baumannii identifiziert werden. Außerdem wurde ein grundlegender Beitrag zur funktionellen Charakterisierung von TufAb sowie p41 von A. baumannii erbracht.
Es konnte nachgewiesen werden, dass gereinigtes TufAb humanes Plasminogen bindet und diese Interaktion teilweise durch Lysin-Reste vermittelt und von der Ionenstärke beeinflusst ist. An TufAb-gebundenes Plasminogen war für den Plasminogen-Aktivator u-PA zugänglich und konnte zu Plasmin aktiviert werden, welches das chromogene Substrat S-2251, das physiologische Substrat Fibrinogen und die zentrale Komplementkomponente C3b proteolytisch spaltete. Schließlich konnte TufAb als „Moonlighting“-Protein auf der Zelloberfläche von A. baumannii identifiziert werden.
Für das Lipoprotein p41 konnte ebenfalls gezeigt werden, dass dieses an Plasminogen bindet. Die Bindung von Plasminogen an p41 erfolgte ebenfalls über Lysin-Reste, zeigte sich allerdings von der Ionenstärke unbeeinflusst. Im Fall von p41 konnte mit Hilfe von C-terminal verkürzten p41-Konstrukten gezeigt werden, dass C-terminale Lysin-Reste an der Bindung von Plasminogen beteiligt sind. Weitere Versuche mit p41-Proteinen, bei welchen vier C-terminale Lysin-Reste durch Alanin-Reste substituiert wurden, ergaben, dass die beiden Lysin-Reste K368 und K369 essentiell für die Bindung von Plasminogen an p41 sind. Zudem konnte gezeigt werden, dass sowohl Kringle-Domäne 1 als auch Kringle-Domäne 4 von Plasminogen bei der Interaktion mit p41 involviert sind. An p41 gebundenes Plasminogen ließ sich durch u-PA zu Plasmin aktivieren, welches Fibrinogen sowie die zentrale Komplementkomponente C3b degradierte. p41 ist außerdem in der Lage, die Komplementkomponenten C3, C3b und C5 zu binden und den alternativen Weg zu inhibieren. Zudem ergaben Untersuchungen im Rahmen dieser Arbeit erste Hinweise darauf, dass zumindest die Plasminogen-bindende Region auf der Zelloberfläche von A. baumannii lokalisiert ist.
Die Inaktivierung des p41-kodierenden Gens führte zu einer signifikanten Abnahme im Überleben von A. baumannii-Zellen in der Gegenwart von NHS. Zudem zeigte die Mutante Δp41 einen Defekt in der Plasmin-abhängigen Transmigration durch einen Endothelzell-Monolayer. Beide Versuche untermauern die physiologische Relevanz für die Interaktion von A. baumannii mit Plasminogen.
Translation elongation factor Tuf of Acinetobacter baumannii is a plasminogen-binding protein
(2015)
Acinetobacter baumannii is an important nosocomial pathogen, causing a variety of opportunistic infections of the skin, soft tissues and wounds, urinary tract infections, secondary meningitis, pneumonia and bacteremia. Over 63% of A. baumannii infections occurring in the United States are caused by multidrug resistant isolates, and pan-resistant isolates have begun to emerge that are resistant to all clinically relevant antibiotics. The complement system represents the first line of defense against invading pathogens. However, many A. baumannii isolates, especially those causing severe bacteremia are resistant to complement-mediated killing, though the underlying mechanisms remain poorly understood. Here we show for the first time that A. baumannii binds host-derived plasminogen and we identify the translation elongation factor Tuf as a moonlighting plasminogen-binding protein that is exposed on the outer surface of A. baumannii. Binding of plasminogen to Tuf is at least partly dependent on lysine residues and ionic interactions. Plasminogen, once bound to Tuf can be converted to active plasmin and proteolytically degrade fibrinogen as well as the key complement component C3b. Thus, Tuf acts as a multifunctional protein that may contribute to virulence of A. baumannii by aiding in dissemination and evasion of the complement system.
This thesis deals with several aspects of non-perturbative calculations in low-dimensional quantum field theories. It is split into two main parts:
The first part focuses on method development and testing. Using exactly integrable QFTs in zero spacetime dimensions as toy models, the need for non-perturbative methods in QFT is demonstrated. In particular, we focus on the functional renormalization group (FRG) as a non-perturbative exact method and present a novel fluid-dynamic reformulation of certain FRG flow equations. This framework and the application of numerical schemes from the field of computational fluid dynamics (CFD) to the FRG is tested and benchmarked against exact results for correlation functions. We also draw several conclusions for the qualitative understanding and interpretation of renormalization group (RG) flows from this fluid-dynamic reformulation and discuss the generalization of our findings to realistic higher-dimensional QFTs.
The topics discussed in the second part are also manifold. In general, the second part of this thesis deals with the Gross-Neveu (GN) model, which is a prototype of a relativistic QFT. Even though being a model in two spacetime dimensions, it shares many features of realistic models and theories for high-energy particle physics, but also emerges as a limiting case from systems in solid state physics. Especially, it is interesting to study the model at non-vanishing temperatures and densities, thus, its thermodynamic properties and phase structure.
First, we use this model to test and apply our findings of the first part of this thesis in a realistic environment. We analyze how the fluid-dynamic aspects of the FRG realize themselves in the RG flow of a full-fledged QFT and how we profit from this numeric framework in actual calculations. Thereby, however, we also aim at answering a long-standing question: Is there still symmetry breaking and condensation at non-zero temperatures in the GN model, if one relaxes the commonly used approximation of an infinite number of fermion species and works with a finite number of fermions? In short: Is matter (in the GN model) in a single spatial dimension at non-zero temperature always gas-like?
In general, we also use the GN model to learn about the correct description of QFTs at non-zero temperatures and densities. This is of utmost relevance for model calculations in low-energy quan- tum chromodynamics (QCD) or other QFTs in medium and we draw several conclusions for the requirements for stable calculations at non-zero chemical potential.
We continue previous investigations of the (inhomogeneous) phase structure of the Gross-Neveu model in a noninteger number of spatial dimensions (1≤d<3) in the limit of an infinite number of fermion species (N→∞) at (non)zero chemical potential μ. In this work, we extend the analysis from zero to nonzero temperature T.
The phase diagram of the Gross-Neveu model in 1≤d<3 spatial dimensions is well known under the assumption of spatially homogeneous condensation with both a symmetry broken and a symmetric phase present for all spatial dimensions. In d=1 one additionally finds an inhomogeneous phase, where the order parameter, the condensate, is varying in space. Similarly, phases of spatially varying condensates are also found in the Gross-Neveu model in d=2 and d=3, as long as the theory is not fully renormalized, i.e., in the presence of a regulator. For d=2, one observes that the inhomogeneous phase vanishes, when the regulator is properly removed (which is not possible for d=3 without introducing additional parameters).
In the present work, we use the stability analysis of the symmetric phase to study the presence (for 1≤d<2) and absence (for 2≤d<3) of these inhomogeneous phases and the related moat regimes in the fully renormalized Gross-Neveu model in the μ,T-plane. We also discuss the relation between "the number of spatial dimensions" and "studying the model with a finite regulator" as well as the possible consequences for the limit d→3.
The phase diagram of the (1+1)-dimensional Gross-Neveu model is reanalyzed for (non-)zero chemical potential and (non-)zero temperature within the mean-field approximation. By investigating the momentum dependence of the bosonic two-point function, the well-known second-order phase transition from the Z2 symmetric phase to the so-called inhomogeneous phase is detected. In the latter phase the chiral condensate is periodically varying in space and translational invariance is broken. This work is a proof of concept study that confirms that it is possible to correctly localize second-order phase transition lines between phases without condensation and phases of spatially inhomogeneous condensation via a stability analysis of the homogeneous phase. To complement other works relying on this technique, the stability analysis is explained in detail and its limitations and successes are discussed in context of the Gross-Neveu model. Additionally, we present explicit results for the bosonic wave-function renormalization in the mean-field approximation, which is extracted analytically from the bosonic two-point function. We find regions -- a so-called moat regime -- where the wave function renormalization is negative accompanying the inhomogeneous phase as expected.
The phase diagram of the (1+1)-dimensional Gross-Neveu model is reanalyzed for (non-)zero chemical potential and (non-)zero temperature within the mean-field approximation. By investigating the momentum dependence of the bosonic two-point function, the well-known second-order phase transition from the Z2 symmetric phase to the so-called inhomogeneous phase is detected. In the latter phase the chiral condensate is periodically varying in space and translational invariance is broken. This work is a proof of concept study that confirms that it is possible to correctly localize second-order phase transition lines between phases without condensation and phases of spatially inhomogeneous condensation via a stability analysis of the homogeneous phase. To complement other works relying on this technique, the stability analysis is explained in detail and its limitations and successes are discussed in context of the Gross-Neveu model. Additionally, we present explicit results for the bosonic wave-function renormalization in the mean-field approximation, which is extracted analytically from the bosonic two-point function. We find regions -- a so-called moat regime -- where the wave function renormalization is negative accompanying the inhomogeneous phase as expected.
The phase diagram of the (1+1)-dimensional Gross-Neveu model is reanalyzed for (non-)zero chemical potential and (non-)zero temperature within the mean-field approximation. By investigating the momentum dependence of the bosonic two-point function, the well-known second-order phase transition from the Z2 symmetric phase to the so-called inhomogeneous phase is detected. In the latter phase the chiral condensate is periodically varying in space and translational invariance is broken. This work is a proof of concept study that confirms that it is possible to correctly localize second-order phase transition lines between phases without condensation and phases of spatially inhomogeneous condensation via a stability analysis of the homogeneous phase. To complement other works relying on this technique, the stability analysis is explained in detail and its limitations and successes are discussed in context of the Gross-Neveu model. Additionally, we present explicit results for the bosonic wave-function renormalization in the mean-field approximation, which is extracted analytically from the bosonic two-point function. We find regions -- a so-called moat regime -- where the wave function renormalization is negative accompanying the inhomogeneous phase as expected.
Gene targeting in embryonic stem (ES) cells remains best practice for introducing complex mutations into the mouse germline. One aspect in this multistep process that has not been streamlined with regard to the logistics and ethics of mouse breeding is the efficiency of germline transmission: the transmission of the ES cell-derived genome through the germline of chimeras to their offspring. A method whereby male chimeras transmit exclusively the genome of the injected ES cells to their offspring has been developed. The new technology, referred to as goGermline, entails injecting ES cells into blastocysts produced by superovulated homozygous Tsc22d3 floxed females mated with homozygous ROSA26-Cre males. This cross produces males that are sterile due to a complete cell-autonomous defect in spermatogenesis. The resulting male chimeras can be sterile but when fertile, they transmit the ES cell-derived genome to 100% of their offspring. The method was validated extensively and in two laboratories for gene-targeted ES clones that were derived from the commonly used parental ES cell lines Bruce4, E14, and JM8A3. The complete elimination of the collateral birth of undesired, non-ES cell-derived offspring in goGermline technology fulfills the reduction imperative of the 3R principle of humane experimental technique with animals. genesis 54:326-333, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc.
The p53-family member p73 plays a role in various cellular signaling pathways during development and growth control and it can have tumor suppressor properties. Several isoforms of p73 exist with considerable differences in their function. Whereas the functions of the N-terminal isoforms (TA and delta Np73) and their opposing pro- and antiapoptotic roles have become evident, the functional differences of the distinct C-terminal splice forms of TAp73 have remained unclear. Here, we characterized the global genomic binding sites for TAp73alpha and TAp73beta by chromatin immunoprecipitation sequencing as well as the transcriptional responses by performing RNA sequencing. We identified a specific p73 consensus binding motif and found a strong enrichment of AP1 motifs in close proximity to binding sites for TAp73alpha. These AP1 motif-containing target genes are selectively upregulated by TAp73alpha, while their mRNA expression is repressed upon TAp73beta induction. We show that their expression is dependent on endogenous c-Jun and that recruitment of c-Jun to the respective AP1 sites was impaired upon TAp73beta expression, in part due to downregulation of c-Jun. Several of these AP1-site containing TAp73alpha-induced genes impinge on apoptosis induction, suggesting an underlying molecular mechanism for the observed functional differences between TAp73alpha and TAp73beta.
Im Rahmen dieser Beispielanalyse werden Aspekte und Phänomene der Textgrammatik (vgl. Rickheit & Schade 2002, Stede 2007) veranschaulicht. Am Beispiel einer privaten E-Mail wird gezeigt, wie ein satzgrenzenüberschreitender Zusammenhang und damit Textkohärenz hergestellt werden kann. Dabei werden vor allem die Besonderheiten eines konzeptionell mündlichen Textes (vgl. Schwitalla 2006) der neuen Medien in Bezug auf Kohärenzherstellung herausgearbeitet.
Die vorliegende Beispielerhebung erfasst und analysiert die Sprachbiographien von Freiburger Studierenden mit Migrationshintergrund. Sprachbiographien dienen der Darstellung eines Lebens bzw. einer Lebensspanne unter dem Gesichtspunkt der Sprachentwicklung mit dem Ziel der Rekonstruktion eines Gesamtbildes der sprachlichen Entwicklung einer Person in ihrem gesellschaftlichen Umfeld. Mithilfe der Sprachbiographien lassen sich Rückschlüsse auf die sprachliche und soziale Identität der Personen sowie auf den Zusammenhang zwischen der individuellen Sprachentwicklung und den für sie relevanten Lebensbedingungen ziehen. Besondere Bedeutung kommt hierbei der Rolle von (sprachlicher) Identität beim Integrationsprozess zu.
Behavior is characterized by sequences of goal oriented conducts, such as food uptake, socializing and resting. Classically, one would define for each task a corresponding satisfaction level, with the agent engaging, at a given time, in the activity having the lowest satisfaction level. Alternatively, one may consider that the agent follows the overarching objective to generate sequences of distinct activities. To achieve a balanced distribution of activities would then be the primary goal, and not to master a specific task. In this setting the agent would show two types of behaviors, task-oriented and task-searching phases, with the latter interseeding the former. We study the emergence of autonomous task switching for the case of a simulated robot arm. Grasping one of several moving objects corresponds in this setting to a specific activity. Overall, the arm should follow a given object temporarily and then move away, in order to search for a new target and reengage. We show that this behavior can be generated robustly when modeling the arm as an adaptive dynamical system. The dissipation function is in this approach time dependent. The arm is in a dissipative state when searching for a nearby object, dissipating energy on approach. Once close, the dissipation function starts to increase, with the eventual sign change implying that the arm will take up energy and wander off. The resulting explorative state ends when the dissipation function becomes again negative and the arm selects a new target. We believe that our approach may be generalized to generate self-organized sequences of activities in general.
The YaeJ protein is a codon-independent release factor with peptidyl-tRNA hydrolysis (PTH) activity, and functions as a stalled-ribosome rescue factor in Escherichia coli. To identify residues required for YaeJ function, we performed mutational analysis for in vitro PTH activity towards rescue of ribosomes stalled on a non-stop mRNA, and for ribosome-binding efficiency. We focused on residues conserved among bacterial YaeJ proteins. Additionally, we determined the solution structure of the GGQ domain of YaeJ from E. coli using nuclear magnetic resonance spectroscopy. YaeJ and a human homolog, ICT1, had similar levels of PTH activity, despite various differences in sequence and structure. While no YaeJ-specific residues important for PTH activity occur in the structured GGQ domain, Arg118, Leu119, Lys122, Lys129 and Arg132 in the following C-terminal extension were required for PTH activity. All of these residues are completely conserved among bacteria. The equivalent residues were also found in the C-terminal extension of ICT1, allowing an appropriate sequence alignment between YaeJ and ICT1 proteins from various species. Single amino acid substitutions for each of these residues significantly decreased ribosome-binding efficiency. These biochemical findings provide clues to understanding how YaeJ enters the A-site of stalled ribosomes.
A convex body is unconditional if it is symmetric with respect to reflections in all coordinate hyperplanes. We investigate unconditional lattice polytopes with respect to geometric, combinatorial, and algebraic properties. In particular, we characterize unconditional reflexive polytopes in terms of perfect graphs. As a prime example, we study the signed Birkhoff polytope. Moreover, we derive constructions for Gale-dual pairs of polytopes and we explicitly describe Gröbner bases for unconditional reflexive polytopes coming from partially ordered sets.
Eisbildende Prozesse sind für die Wolkenbildung von großer Bedeutung und haben erhebliche Auswirkungen auf das Wetter und Klima der Erde, indem sie den Strahlungsantrieb und die Niederschlagsbildung beeinflussen. In den mittleren Breiten entsteht der meiste Niederschlag in sogenannten Mischphasenwolken (MPC), welche sowohl aus unterkühlten Wolkentröpfchen als auch aus Eiskristallen bestehen. Bei Temperaturen zwischen 0°C und -38°C erfolgt die Bildung von Eiskristallen in MPC in Gegenwart von Aerosolpartikeln, die als sogenannte Eiskeime (INP) die Fähigkeit besitzen, auf ihrer Oberfläche Eis zu nukleieren. Trotz der großen wissenschaftlichen Fortschritte in den letzten Jahrzehnten, weist der heterogene Eisbildungsprozess, als einer der wichtigsten in der Atmosphäre auftretenden Aerosol-Wolken-Wechselwirkungsprozesse, immer noch große Unsicherheiten auf. Um zukünftige Klimavorhersagen und -projektionen in Modellen besser abbilden zu können, ist es somit notwendig den Wissensgrad der räumlichen und zeitlichen Heterogenität von INP in Bezug auf Herkunft, Anzahl und Zusammensetzung zu erhöhen. Im Zentrum dieser Arbeit steht der Eiskeimzähler FINCH (Fast Ice Nucleus Chamber), der für Labor- und Feldexperimente von der Johann Wolfgang Goethe-Universität in Frankfurt am Main entwickelt wurde. Durch das Mischen des Probenstroms mit einem warm-feuchten und einem kalten-trockenen Luftstrom wird eine Übersättigung in der in-situ Eiskammer erreicht, die benötigt wird, eisbildende Partikel zu aktivieren. Die aktivierten Partikel können beim Durchströmen der Kammer zu Wassertropfen oder Eiskristallen anwachsen. Am Ausgang der Kammer wird die Anzahl und Größe der Partikel durch die FINCH-Optik erfasst. Als grundlegender Schritt und aufbauend auf den Charakterisierungsmessungen von Frank (2017) wurden in der vorliegenden Arbeit die Leistung, die Zuverlässigkeit sowie die Reproduzierbarkeit von FINCH in Validierungsexperimenten im Labor überprüft. Im Zuge dessen wurden heterogene Gefrierexperimente mit definierten Referenzaerosolproben (bspw. K-Feldspat) bei wasserübersättigten Bedingungen und verschiedenen Gefriertemperaturen durchgeführt. Für den Großteil der erzielten Resultate konnte eine zufriedenstellende Übereinstimmung mit Literaturwerten von anderen INP-Messinstrumenten aus der ganzen Welt erzielt werden. Es zeigte sich, dass die Leistungsfähigkeit von FINCH messtechnische Limitationen für Messexperimente bei Temperaturen >-10°C und <-30°C aufweist, was eine Einschränkung des Messbereichs bedeutet. Hinsichtlich der Quantifizierung des Unsicherheitsbereiches des Messgerätes in Bezug auf Temperatur und relativer Feuchte bedarf es im Nachgang an dieser Arbeit weiterer Charakterisierungsmessungen. Im Rahmen der Ice Nuclei Research Unit (INUIT) Forschergruppe wurde FINCH mit einem gepumpten Gegenstrom-Impaktor PCVI und dem online Einzelpartikel-Massenspektrometer ALABAMA gekoppelt. Diese spezielle Messmethodik dient zur chemischen und mikrophysikalischen Charakterisierung der INP und der Eispartikelresiduen (IPR). Der Fokus lag zunächst darauf die Funktionalität des gekoppelten Messsystems im Labor zu überprüfen. Ausführliche Charakterisierungsmessungen zeigten unter eisübersättigten und unterkühlten Bedingungen, dass das Prinzip der Trennung der INP von nicht-aktivierten Aerosolen und unterkühlten Tropfen hinter FINCH durch den PCVI funktioniert. Ebenso konnten erste quantitative Aussagen zur chemischen Zusammensetzung der IPR getroffen werden. Es zeigte sich, dass bei den Aktivierungsexperimenten ein geringer Anteil an Partikeltypen metallischer Art von ALABAMA detektiert wurden, der nicht dem untersuchten Aerosoltyp zugeordnet werden konnte. Der Ursprung dieser Kontamination konnte im Rahmen dieser Arbeit nicht abschließend geklärt werden und bedarf weiterer Validierungsmessungen im Labor. Atmosphärische Eiskeimkonzentrationen wurden im Rahmen von Feldmesskampagnen an der Hochalpinen Forschungsstation Jungfraujoch (JFJ) in den Schweizer Alpen und am Campus Riedberg der Johann Wolfgang Goethe-Universität in Frankfurt am Main untersucht. Hier konnten erste Erfahrungen mit Außenluftmessungen bezüglich der Leistungsfähigkeit und der Nachweisgrenze (LOD) des Messgerätes gesammelt werden. Durch den Einfluss der freien Troposphäre am JFJ waren die Messungen hauptsächlich von aerosolpartikelarmer Luft mit einer geringen Anzahl von Eiskeimen geprägt, so dass sich die gemessenen INP-Konzentrationen oftmals unter die Nachweisgrenze von FINCH fielen. Unter Einsatz eines Aerosolkonzentrators konnte die Detektionseffizienz verbessert und das LOD herabgesetzt werden. Am JFJ wurden die INP im Mittel bei einer Temperatur von -23°C und einem Wassersättigungsverhältnis von 107% beprobt. Die mediane (mittlere) INP-Konzentration inklusive LOD lag bei 2,1 (3,3) sL-1 und oberhalb des LOD bei 3,1 (4,5) sL-1. Ein Vergleich mit den Messungen am Campus Riedberg unter annähernd gleichen Bedingungen resultiert in ähnlichen Konzentrationen.
Treffen im Titel eines Sammelbandes zwei Worte aufeinander, die auf einigermaßen aktuelle kulturwissenschaftliche "Turns" verweisen, im vorliegenden Fall auf den "Iconic" und den "Performative Turn", so liegt der Verdacht nahe, dass hier entweder alter Wein in neue Schläuche verpackt wird oder dass modische Schlagworte inhaltliche Leere verdecken sollen. Beide Befürchtungen erweisen sich im vorliegenden Band glücklicherweise als unbegründet. Stattdessen zeigt sich deutlich, wie gerade das Konzept der Performanz zu einem neuen Verständnis der Rolle von Bildern und ihrer Wirksamkeit im hoch- und spätmittelalterlichen lateinischen Europa beitragen kann. Um diesen zeitlichen und räumlichen Schwerpunkt herum, der sich aus der Zusammenarbeit der Brüsseler Groupe de recherche en histoire médiéval (GRHM) und der Pariser Groupe d’anthropologie historique de l’Occident médiéval (GAHOM) ergibt, versammeln sich Beiträge, die zudem auch die (christliche) Antike, Byzanz, die Frühe Neuzeit und sogar das 20. und 21. Jahrhundert in den Blick nehmen. ...
Der Beitrag beschäftigt sich mit der historischen Überlieferung zu Burgen und anderen Befestigungen zwischen ca. 750 und 900 u. Z. Anhand von vier Beispielen aus unterschiedlichen Quellengattungen wird gezeigt, dass Befestigungen ein zentraler Bestandteil der karolingischen Welt waren. Die Bezeichnungen für Befestigungen umfassen ein großes terminologisches Spektrum, das sich mit den Begriffen deckt, die auch für städtische Siedlungen verwendet wurden (urbs, civitas, castellum, oppidum). Dies zeigt, dass Befestigungen und städtische Siedlungsformen zeitgenössisch nicht konsequent unterschieden wurden. Sie müssen daher zusammen betrachtet werden. Im zweiten Teil des Beitrags geht es um die Träger von Befestigungen, zunächst um die fränkischen Könige, die man in der Forschung zumeist für die alleinigen Träger des Burgenbaus hält. Aber auch andere Träger waren bedeutend: Bischöfe übernahmen die Verantwortung für die Befestigungen ihrer Städte, wie an den Beispielen Worms und Rom gezeigt wird, und auch Laien, wie etwa die bayerische Familie der „Waltriche“ und der Franke Iring, verfügten über Burgen. Unterhalten und erbaut wurden Burgen in fränkischer Zeit mithilfe von Dienstverpflichtungen, die für alle Freien galten, aber auch im Rahmen von Grundherrschaften.
Seit jeher haben Konfliktparteien die Kontrolle über die Wasserversorgung genutzt, um ihre Herrschaft zu stabilisieren, Gegner zu schwächen oder territoriale Gewinne zu erzielen. Durch den globalen Klimawandel und die damit verbundene Wasserknappheit wird diese Praxis noch wirksamer und schädlicher. Um das Bewusstsein für dieses lang vernachlässigte Phänomen zu schärfen und die betroffene Bevölkerung zu unterstützen, ist ein interdisziplinärer Forschungsansatz unabdingbar.
Am 30.11.2023 eröffnete die Ausstellung „Bilder werfen: Grabungsarbeiten zur studentischen Filmkultur in Frankfurt“ im Schopenhauer-Studio, dem Kommunikations- und Ausstellungsraum der Universitätsbibliothek. Sie widmet sich der Geschichte der Film- und Kinoarbeit an der Goethe-Universität, von der Gründung des Film-Studios 1951 bis heute in Form der Pupille – Kino in der Uni...
Gutartige Schilddrüsenknoten stellen ein häufiges klinisches Problem dar, bei dem minimalinvasive, thermoablative Therapien wie die Radiofrequenzablation (RFA), als Alternative zur chirurgischen Behandlung, immer relevanter werden. Da es sich bei den Beschwerden oftmals um Symptome handelt, die von der lokalen Raumforderung und Größe abhängen, ist die Reduktion des Knotenvolumens ein zentraler Bestandteil der Therapie. Hierbei stellt die bipolare RFA eine neuartige Technologie zur minimalinvasiven Behandlung von gutartigen Schilddrüsenknoten dar und soll die Nachteile der monopolaren RFA, die das bislang am häufigsten verwendete System darstellt, überwinden. Jedoch gibt es aktuell keine offiziellen Leitlinien bezüglich der zu verwendenden Ablationstechnik. Aus diesem Grund war die Zielrichtung dieser Arbeit, erstmalig die Behandlung gutartiger Schilddrüsenknoten mittels bipolarer RFA in Kombination mit der sogenannten multiple overlapping shot technique („MOST“) anhand der Volumenreduktion nach 3 Monaten zu untersuchen. Hierzu wurden 18 Patienten (4 männliche, 14 weibliche Patienten; mittleres Alter: 50 Jahre, Altersspannweite: 15–72 Jahre) mit insgesamt 20 gutartigen Schilddrüsenknoten (17 hypofunktionelle und 3 hyperfunktionelle Knoten) behandelt und anschließend sonographisch ausgewertet. Mit einer medianen Volumen-reduktion (ΔV) von 5,3 ml (Spannweite: 0,13– 43,1 ml) nach 3 Monaten, was einer mittleren relativen Volumenreduktion von 56 ± 17,9 % entspricht, ergab sich ein signifikantes (p < 0,0001) Ergebnis. Das mediane Knotenvolumen reduzierte sich von anfangs 8 ml (Spannweite: 0,48– 62 ml) auf 2,3 ml (Spannweite: 0,3–32 ml) bei der Kontrolluntersuchung. Es kam bei allen Knoten zu einer Volumenreduktion, welche in 70 % der Fälle über 50 % betrug. Schwere Komplikationen wie anhaltende Stimmveränderungen, Nervenläsionen, Knoten-rupturen und Infektionen, ebenso wie immunogene Überfunktionen oder persistierende Schmerzen, traten während des Follow-ups nicht auf. Alle Patienten mit hypofunktionellen Knoten (15) blieben euthyreot, während sich Patienten mit hyperfunktionellen Knoten zum Zeitpunkt der Kontrolluntersuchung entweder in einer euthyreoten (2) oder latent hypothyreoten (1) Stoffwechsellage befanden. Ein medikationspflichtiger Hypothyreoidismus entstand bei keinem der Patienten. Daher stellt die bipolare RFA in Kombination mit der angewandten MOST ein effektives und sicheres thermoablatives Verfahren für die Behandlung gutartiger Schilddrüsenknoten dar.
Hintergrund: Aphasien gehören nicht zu den typischen klinischen Manifestationen lakunärer Hirninfarkte, sind jedoch im Rahmen seltener atypischer lakunärer Syndrome beschrieben.
Ziel der Arbeit: Beschreibung von Aphasiemustern und betroffener Fasertrakte bei lakunären Infarkten.
Material und Methoden: Fallserie von drei Patienten mit in der Magnetresonanztomographie nachgewiesenen lakunären Hirninfarkten und Aphasie. Identifikation betroffener Faserbahnen mittels Fasertraktographie der koregistrierten Schädigungsorte in Gehirnen zweier gesunder Probanden.
Ergebnisse: Radiologisch waren die Lakunen, die Aphasien hervorriefen, weit lateral im Marklager der linken Hemisphäre gelegen und befanden sich im Vergleich zu der Lakune eines nichtaphasischen Kontrollpatienten weiter rostrodorsal. Klinisch fand sich trotz Aussparung des Kortex, Thalamus und weiter Teile der Basalganglien eine leichte bis moderate nichtflüssige Aphasie mit syntaktischen Defiziten. In der Fasertraktographie zeigten die aphasischen im Vergleich zum nichtaphasischen Patienten eine stärkere Affektion der Fasern des linken Fasciculus arcuatus sowie eine Beteiligung des frontostriatalen und frontalen Aslant-Trakts.
Diskussion: Links lateral gelegene lakunäre Infarkte können durch Beteiligung sprachrelevanter Fasertrakte eine klinisch relevante Aphasie hervorrufen.
Einleitung: Die stereotaktische Laserthermoablation (SLTA) stellt eine minimal-invasive Behandlung für therapierefraktäre Epilepsien auf dem Boden eines hypothalamischen Hamartoms (HH) dar. Durch die weitreichenden Folgen einer therapierefraktären Epilepsie können hohe direkte Kosten entstehen, die durch eine zu erzielende Anfallsfreiheit gesenkt werden können.
Methoden: Anhand einer Patientin mit einem HH sollen die Auswirkungen einer solchen Erkrankung beleuchtet und der Krankheitsverlauf nach erfolgter SLTA dargestellt werden. Zur Beurteilung der Kosteneffizienz der SLTA wurden die direkten Kosten, basierend auf den Krankenversicherungsdaten der Patientin, über die Versicherungsjahre 2017 bis 2020 analysiert.
Ergebnisse:
Bei der Patientin bestand eine hochaktive, medikamentenrefraktäre Epilepsie mit erhöhtem Verletzungsrisiko und zunehmender Verschlechterung der schulischen Leistung und der psychischen Verfassung. Begleitend bestand durch das HH eine Pubertas praecox. Nach SLTA entwickelte die Patientin mit einem Follow-up von 26 Monaten eine vollständige Anfallsfreiheit sowie eine endokrinologische Stabilisierung, sodass die antikonvulsive als auch die hormonelle Medikation im Verlauf beendet werden konnten. Relevante persistierende Komplikationen wurden nicht beobachtet. Die direkten jährlichen Kosten (stationär [ausschließlich der SLTA selbst]/ambulant/Medikamente) reduzierten sich von € 6603 in 2017 und € 12.903 in 2018 auf € 3609 in 2019 und zuletzt € 617 in 2020, was einer Reduktion von bis zu 95 % (2018 gegenüber 2020) entsprach. Zusätzlich konnten die Kosten einer geplanten Integrationsassistenz von schätzungsweise € 18.000/Jahr eingespart werden.
Schlussfolgerung: Die SLTA stellt eine effektive und risikoarme Behandlung von HH dar und führt bereits nach 2 Jahren zu einer relevanten Einsparung der direkten Kosten, was bei der Kosten-Nutzen-Abwägung der SLTA einzubeziehen ist.
Background: Mechanical thrombectomy and systemic thrombolysis are important therapies for stroke patients. However, there is disagreement about the accompanying risk of acute symptomatic seizures.
Methods: A retrospective analysis of patients with an acute ischaemic stroke caused by large vessel occlusion was performed. The patients were divided into four groups based on whether they received either mechanical thrombectomy (MT) or systemic thrombolysis (ST; group 1: MT+/ST−; group 2: MT+/ST+; group 3: MT−/ST+; group 4: MT−/ST−). Propensity score matching was conducted for each group combination (1:3, 1:4, 2:3, 2:4, 1:2, 3:4) using the covariates “NIHSS at admission”, “mRS prior to event” and “age”. The primary endpoint was defined as the occurrence of acute symptomatic seizures.
Results: A total of 987 patients met the inclusion criteria, of whom 208, 264, 169 and 346 belonged to groups 1, 2, 3 and 4, respectively. Propensity score matched groups consisted of 160:160, 143:143, 156:156, 144:144, 204:204 and 165:165 patients for the comparisons 1:3, 1:4, 2:3, 2:4, 1:2 and 3:4, respectively. Based on chi-squared tests, there was no significant difference in the frequency of acute symptomatic seizures between the groups. Subgroups varied in their frequency of acute symptomatic seizures, ranging from 2.8 to 3.8%, 2.8–4.4%, 3.6–3.8% and 4.9–6.3% in groups 1, 2, 3 and 4, respectively.
Conclusion: There was no association between MT or ST and an increased risk of acute symptomatic seizures in patients with an acute ischaemic stroke caused by large vessel occlusion who were treated at a primary stroke centre.
Magnetic resonance-guided laser interstitial laser therapy (MRgLITT) and radiofrequency ablation (RFA) represent two minimally invasive methods for the treatment of drug-refractory mesial temporal lobe epilepsy (mTLE). We performed a systematic review and a meta-analysis to compare outcomes and complications between MRgLITT, RFA, and conventional surgical approaches to the temporal lobe (i.e., anterior temporal lobe resection [ATL] or selective amygdalohippocampectomy [sAHE]). Forty-three studies (13 MRgLITT, 6 RFA, and 24 surgery studies) involved 554, 123, 1504, and 1326 patients treated by MRgLITT, RFA, ATL, or sAHE, respectively. Engel Class I (Engel-I) outcomes were achieved after MRgLITT in 57% (315/554, range = 33.3%–67.4%), RFA in 44% (54/123, range = 0%–67.2%), ATL in 69% (1032/1504, range = 40%–92.9%), and sAHE in 66% (887/1326, range = 21.4%–93.3%). Meta-analysis revealed no significant difference in seizure outcome between MRgLITT and RFA (Q = 2.74, p = .098), whereas ATL and sAHE were both superior to MRgLITT (ATL: Q = 8.92, p = .002; sAHE: Q = 4.33, p = .037) and RFA (ATL: Q = 6.42, p = .0113; sAHE: Q = 5.04, p = .0247), with better outcome in patients at follow-up of 60 months or more. Mesial hippocampal sclerosis (mTLE + hippocampal sclerosis) was associated with significantly better outcome after MRgLITT (Engel-I outcome in 64%; Q = 8.55, p = .0035). The rate of major complications was 3.8% for MRgLITT, 3.7% for RFA, 10.9% for ATL, and 7.4% for sAHE; the differences did not show statistical significance. Neuropsychological deficits occurred after all procedures, with left-sided surgeries having a higher rate of verbal memory impairment. Lateral functions such as naming or object recognition may be more preserved in MRgLITT. Thermal therapies are effective techniques but show a significantly lower rate of Engel-I outcome in comparison to ATL and sAHE. Between MRgLITT and RFA there were no significant differences in Engel-I outcome, whereby the success of treatment seems to depend on the approach used (e.g., occipital approach). MRgLITT shows a similar rate of complications compared to RFA, whereas patients undergoing MRgLITT may experience fewer major complications compared to ATL or sAHE and might have a more beneficial neuropsychological outcome.
Background: Patients with epilepsy often require a specialized treatment, which may differ because of the responsibility of the federal states for healthcare policy in Germany.
Objective: State-specific differences in healthcare structures based on inpatient hospital cases of epilepsy patients between 2000 and 2020 in relation to specialized treatment offers.
Material and methods: The inpatient hospital cases of the German federal states were evaluated using the Friedman test and time series trend analysis. A state-specific inpatient undertreatment or overtreatment of inpatient hospital cases outside the registered state was analyzed by comparing residence-related and treatment site-related case numbers with a threshold of ±5%.
Results: After age adjustment, significantly more inpatient cases were found in the “new states” compared to the “old states” (p < 0.001); the highest number of cases nationwide was found in Saarland with 224.8 ± 11.5 cases per 100,000 inhabitants. The trend analysis showed an increase in cases until the end of 2016 with a trend reversal from 2017 and a further significant decrease in hospital cases in the COVID year 2020. A relative inpatient undertreatment was shown for Brandenburg, Lower Saxony, Rhineland-Palatinate, Saxony-Anhalt, Schleswig-Holstein and Thuringia. Additional, possibly compensatory, inpatient care was found for all city states (Hamburg, Bremen and Berlin) and Baden-Wuerttemberg. In federal states with a relative inpatient undertreatment and/or high inpatient hospital case numbers, there was often a lower availability of specialized epilepsy centers, specialized outpatient clinics and epilepsy outpatient clinics.
Conclusion: In Germany there are state-specific differences in the structure of care, with higher inpatient hospital care in the “new states” and Saarland. In addition, there were federal states with disproportionately higher treatment of patients not registered in this federal state. A potential influencing factor may be the availability of centers with specialized treatment for epilepsy patients.
Beim Stichwort Inquisition fällt der Blick zumeist nach Spanien, Portugal oder Italien und nicht auf das Alte Reich, denn dort wurde die Inquisition im Gegensatz zum Süden Europas nie institutionalisiert. Die Frage, warum es im Alten Reich nicht zur Einführung von Tribunalen kam und in welchen anderen Formen die Inquisition dort agierte, stand im Herbst 2009 im Zentrum einer Tagung, deren Ergebnisse nun in einem Sammelband vorliegen. Die Aktivitäten der Inquisition werden nicht nur für den deutschen Sprachraum analysiert, sondern auch mit anderen Ländern in Bezug gesetzt und verglichen. Dies erscheint sinnvoll, da die Inquisition und ihre Rezeption im Alten Reich ohne den Einbezug ihres Wirkens in den romanischen Ländern nicht beurteilt werden kann. Trotz der internationalen Bezüge stammen alle Beiträge, bis auf eine Ausnahme, aus der Feder deutschsprachiger Autoren. Es fällt dann auch auf, dass die spanische Inquisition – abgesehen von den Tribunalen in den spanischen Niederlanden – im Gegensatz zur italienischen und portugiesischen nicht thematisiert wird. Auch in der Einführung wird so gut wie keine aktuelle spanische Literatur genannt. Hier zeigt sich, dass ihre Erforschung auf deutscher Seite bisher kaum betrieben noch rezipiert wurde. Auch die zentrale Frage, ob es Pläne zur Institutionalisierung einer Inquisition in einzelnen katholischen Territorien gab, ist nach wie vor ein Forschungsdesiderat. Auszuschließen ist diese Möglichkeit laut den Herausgebern nicht. Warum es nicht dazu kam, wird mit der Durchsetzung des landesherrlichen Kirchenregiments begründet sowie mit Vorbehalten der Fürsten, für die eine institutionalisierte Inquisition eine Beschränkung ihrer Herrschaftsrechte bedeutet hätte. ...
Acute kidney injury is associated with mortality in COVID-19 patients. However, host cell changes underlying infection of renal cells with SARS-CoV-2 remain unknown and prevent understanding of the molecular mechanisms that may contribute to renal pathology. Here, we carried out quantitative translatome and whole-cell proteomics analyses of primary renal proximal and distal tubular epithelial cells derived from human donors infected with SARS-CoV-2 or MERS-CoV to disseminate virus and cell type–specific changes over time. Our findings revealed shared pathways modified upon infection with both viruses, as well as SARS-CoV-2-specific host cell modulation driving key changes in innate immune activation and cellular protein quality control. Notably, MERS-CoV infection–induced specific changes in mitochondrial biology that were not observed in response to SARS-CoV-2 infection. Furthermore, we identified extensive modulation in pathways associated with kidney failure that changed in a virus- and cell type–specific manner. In summary, we provide an overview of the effects of SARS-CoV-2 or MERS-CoV infection on primary renal epithelial cells revealing key pathways that may be essential for viral replication.
Division of labor and task specialization explain the success of human and insect societies. Social insect colonies are characterized by division of labor, with workers specializing in brood care early and foraging later in life. Theory posits that this task switching requires shifts in responsiveness to task-related cues, yet experimental evidence is weak. Here, we show that a Vitellogenin (Vg) ortholog identified in an RNAseq study on the ant T. longispinosus is involved in this process: using phylogenetic analyses of Vg and Vg-like genes, we firstly show that this candidate gene does not cluster with the intensively studied honey bee Vg but falls into a separate Vg-like A cluster. Secondly, an experimental knockdown of Vg-like A in the fat body caused a reduction in brood care and an increase in nestmate care in young ant workers. Nestmate care is normally exhibited by older workers. We demonstrate experimentally that this task switch is at least partly based on Vg-like A–associated shifts in responsiveness from brood to worker cues. We thus reveal a novel mechanism leading to early behavioral maturation via changes in social cue responsiveness mediated by Vg-like A and associated pathways, which proximately play a role in regulating division of labor.
This work focuses on the investigation of K+, K- and ϕ-meson production in Ag(1.58 A GeV)+Ag collisions. The energetically cheapest channel for direct K+ production in binary NN-collisions NN→NΛK+ lies at exactly this energy. For the remaining K- and ϕ-mesons, an excess energy of 0.31 GeV and 0.34 GeV in the centre of mass system has to be provided by the system. This makes these particles an excellent probe for effects inside the medium.
K+ and K- mesons can be reconstructed directly as they possess a cτ of approximately 3.7 m. Using the approximately 3 billion recorded Ag(1.58 A GeV)+Ag 0-30% most central collision events, all reconstructed K+ and K- within the detector acceptance are investigated for their kinematic properties and their particle production rates compared to a selection of existing models.
Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.
Cytochrome c oxidases (CcOs), members of the heme-copper containing oxidase (HCO) superfamily, are the terminal enzymes of aerobic respiratory chains. The cbb3-type cytochrome c oxidases (cbb3-CcO) form the C-family and have only the central catalytic subunit in common with the A- and B-family HCOs. In Pseudomonas stutzeri, two cbb3 operons are organized in a tandem repeat. The atomic structure of the first cbb3 isoform (Cbb3-1) was determined at 3.2 Å resolution in 2010 (S. Buschmann, E. Warkentin, H. Xie, J. D. Langer, U. Ermler, and H. Michel, Science 329:327-330, 2010, http://dx.doi.org/10.1126/science.1187303). Unexpectedly, the electron density map of Cbb3-1 revealed the presence of an additional transmembrane helix (TMH) which could not be assigned to any known protein. We now identified this TMH as the previously uncharacterized protein PstZoBell_05036, using a customized matrix-assisted laser desorption ionization (MALDI)-tandem mass spectrometry setup. The amino acid sequence matches the electron density of the unassigned TMH. Consequently, the protein was renamed CcoM. In order to identify the function of this new subunit in the cbb3 complex, we generated and analyzed a CcoM knockout strain. The results of the biochemical and biophysical characterization indicate that CcoM may be involved in CcO complex assembly or stabilization. In addition, we found that CcoM plays a role in anaerobic respiration, as the ΔCcoM strain displayed altered growth rates under anaerobic denitrifying conditions.om Pseudomonas stutzeri, a bacterium closely related to the human pathogen Pseudomonas aeruginosa.
Testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by RT-PCR is a vital public health tool in the pandemic. Self-collected samples are increasingly used as an alternative to nasopharyngeal swabs. Several studies suggested that they are sufficiently sensitive to be a useful alternative. However, there are limited data directly comparing several different types of self-collected materials to determine which material is preferable. A total of 102 predominantly symptomatic adults with a confirmed SARS-CoV-2 infection self-collected native saliva, a tongue swab, a mid-turbinate nasal swab, saliva obtained by chewing a cotton pad and gargle lavage, within 48 h of initial diagnosis. Sample collection was unsupervised. Both native saliva and gargling with tap water had high diagnostic sensitivity of 92.8% and 89.1%, respectively. Nasal swabs had a sensitivity of 85.1%, which was not significantly inferior to saliva (p = 0.092), but 16.6% of participants reported they had difficult in self-collection of this sample. A tongue swab and saliva obtained by chewing a cotton pad had a significantly lower sensitivity of 74.2% and 70.2%, respectively. Diagnostic sensitivity was not related to the presence of clinical symptoms or to age. When comparing self-collected specimens from different material, saliva, gargle lavage or mid-turbinate nasal swabs may be considered for most symptomatic patients. However, complementary experiments are required to verify that differences in performance observed among the five sampling modes were not attributed to collection impairment.
Background: To minimize the risk of disease transmission in cornea transplantation, donor screening for blood-derived viral infections is mandatory. Ideally, pre-mortem blood samples are used, but based on availability, cadaveric blood samples of cornea donors may also be used. However, serological and nucleic acid amplification tests (NATs) need to be validated for the use of cadaveric specimens.
Methods: Hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV) 1/2, and Treponema pallidum (syphilis)-specific serological and/or NAT assays were validated on different platforms (Abbott Alinity i, Alinity m, Roche Cobas 6800, and Roche Cobas AmpliPrep/Cobas TaqMan (CAP/CTM)) using (un)spiked paired pre- and post-mortem cornea donor blood samples from the same individual (up to 23.83 h after death) of 28 individuals in accordance with the specifications of the German Federal Institute for Vaccines and Biomedicines (Paul-Ehrlich-Institut [PEI]). In addition, routinely HBV-, HCV- and HIV-PCR-negative tested post-mortem blood samples of 24 individuals were used to assess NAT specificity.
Results: For the majority of serological parameters on the Abbott Alinity i (HBsAg, anti-HBc, anti-HBs, anti-HCV, anti-HIV, anti-HTLV 1/2, and anti-Treponema pallidum), ratios of generated test results of (un)spiked paired pre- and post-mortem blood samples differed ≤25%, with an agreement of qualitative pre- and post-mortem test results ranging from 91.2 to 100%. For NAT parameters (HBV, HCV, and HIV) on the Cobas 6800, Alinity m, and CAP/CTM, no significant deviation in virus concentrations (factor >5) of spiked pre- and post-mortem blood samples could be observed. Ct-values of corresponding internal controls did also not differ significantly (>1.5 Ct-values). In addition, no false-positive test results were generated when specificity was assessed.
Conclusion: Overall, fluctuations of test results for serological and NAT parameters in pre- and post-mortem blood samples examined in this study, were only limited and within the range of what is also observed when routinely testing fresh patient specimens. We conclude that all examined assays are eligible for the screening of blood samples taken up to about 24 h after the occurrence of death.
The plaque reduction neutralization test (PRNT) is a preferred method for the detection of functional, SARS-CoV-2 specific neutralizing antibodies from serum samples. Alternatively, surrogate enzyme-linked immunosorbent assays (ELISAs) using ACE2 as the target structure for the detection of neutralization-competent antibodies have been developed. They are capable of high throughput, have a short turnaround time, and can be performed under standard laboratory safety conditions. However, there are very limited data on their clinical performance and how they compare to the PRNT. We evaluated three surrogate immunoassays (GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (GenScript Biotech, Piscataway Township, NJ, USA), the TECO® SARS-CoV-2 Neutralization Antibody Assay (TECOmedical AG, Sissach, Switzerland), and the Leinco COVID-19 ImmunoRank™ Neutralization MICRO-ELISA (Leinco Technologies, Fenton, MO, USA)) and one automated quantitative SARS-CoV-2 Spike protein-based IgG antibody assay (Abbott GmbH, Wiesbaden, Germany) by testing 78 clinical samples, including several follow-up samples of six BNT162b2 (BioNTech/Pfizer, Mainz, Germany/New York, NY, USA) vaccinated individuals. Using the PRNT as a reference method, the overall sensitivity of the examined assays ranged from 93.8 to 100% and specificity ranged from 73.9 to 91.3%. Weighted kappa demonstrated a substantial to almost perfect agreement. The findings of our study allow these assays to be considered when a PRNT is not available. However, the latter still should be the preferred choice. For optimal clinical performance, the cut-off value of the TECO assay should be individually adapted.
Objectives: Regarding reactogenicity and immunogenicity, heterologous COVID-19 vaccination regimens are considered as an alternative to conventional immunization schemes.
Methods: Individuals receiving either heterologous (ChAdOx1-S [AstraZeneca, Cambridge, UK]/BNT162b2 [Pfizer-BioNTech, Mainz, Germany]; n = 306) or homologous (messenger RNA [mRNA]-1273 [Moderna, Cambridge, Massachusetts, USA]; n = 139) vaccination were asked to participate when receiving their second dose. Reactogenicity was assessed after 1 month, immunogenicity after 1, 3, and/or 6 months, including a third dose, through SARS-CoV-2 antispike immunoglobulin G, surrogate virus neutralization test, and a plaque reduction neutralization test against the Delta (B.1.167.2) and Omicron (B.1.1.529; BA.1) variants of concern.
Results: The overall reactogenicity was lower after heterologous vaccination. In both cohorts, SARS-CoV-2 antispike immunoglobulin G concentrations waned over time with the heterologous vaccination demonstrating higher neutralizing activity than homologous mRNA vaccination after 3 months to low neutralizing levels in the Delta plaque reduction neutralization test after 6 months. At this point, 3.2% of the heterologous and 11.4% of the homologous cohort yielded low neutralizing activity against Omicron. After a third dose of an mRNA vaccine, ≥99% of vaccinees demonstrated positive neutralizing activity against Delta. Depending on the vaccination scheme and against Omicron, 60% to 87.5% of vaccinees demonstrated positive neutralizing activity.
Conclusion: ChAdOx1-S/BNT162b2 vaccination demonstrated an acceptable reactogenicity and immunogenicity profile. A third dose of an mRNA vaccine is necessary to maintain neutralizing activity against SARS-CoV-2. However, variants of concern-adapted versions of the vaccines would be desirable.
Due to globally rising numbers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, resources for real-time reverse-transcription polymerase chain reaction (rRT-PCR)-based testing have been exhausted. In order to meet the demands of testing and reduce transmission, SARS-CoV-2 antigen-detecting rapid diagnostic tests (Ag-RDTs) are being considered. These tests are fast, inexpensive, and simple to use, but whether they detect potentially infectious cases has not been well studied. We evaluated three lateral flow assays (RIDA®QUICK SARS-CoV-2 Antigen (R-Biopharm), SARS-CoV-2 Rapid Antigen Test (Roche)), and NADAL® COVID-19 Ag Test (Nal von Minden GmbH, Regensburg, Germany) and one microfluidic immunofluorescence assay (SARS-CoV-2 Ag Test (LumiraDx GmbH, Cologne, Germany)) using 100 clinical samples. Diagnostic rRT-PCR and cell culture testing as a marker for infectivity were performed in parallel. The overall Ag-RDT sensitivity for rRT-PCR-positive samples ranged from 24.3% to 50%. However, for samples with a viral load of more than 6 log10 RNA copies/mL (22/100), typically seen in infectious individuals, Ag-RDT positivity was between 81.8% and 100%. Only 51.6% (33/64) of the rRT-PCR-positive samples were infectious in cell culture. In contrast, three Ag-RDTs demonstrated a more significant correlation with cell culture infectivity (61.8–82.4%). Our findings suggest that large-scale SARS-CoV-2 Ag-RDT-based testing can be considered for detecting potentially infective individuals and reducing the virus spread.
As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay.
For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated.
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) serological assays are urgently needed for rapid diagnosis, contact tracing, and for epidemiological studies. So far, there is limited data on how commercially available tests perform with real patient samples, and if positive tested samples show neutralizing abilities. Focusing on IgG antibodies, we demonstrate the performance of two enzyme‐linked immunosorbent assay (ELISA) assays (Euroimmun SARS‐CoV‐2 IgG and Vircell COVID‐19 ELISA IgG) in comparison to one lateral flow assay (FaStep COVID‐19 IgG/IgM Rapid Test Device) and two in‐house developed assays (immunofluorescence assay [IFA] and plaque reduction neutralization test [PRNT]). We tested follow up serum/plasma samples of individuals polymerase chain reaction‐diagnosed with COVID‐19. Most of the SARS‐CoV‐2 samples were from individuals with moderate to the severe clinical course, who required an in‐patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5‐9) and from 93.8% to 100% for the later period (days 10‐18).
Die exakte Positionierung von Intraokularlinsen in den Kapselsack ist von entscheidender Bedeutung für das postoperative visuelle Ergebnis nach Kataraktoperation oder refraktivem Linsenaustausch. Schon leichte Dezentrierungen können optische Aberrationen hervorrufen welche das Sehen der Patienten negativ beeinflussen. Besonders kommt dieses Phänomen bei sog. Premium Intraokularlinsen mit speziellen Optiken (asphärisch, torisch oder multifokal, sowie Kombinationen dieser) zum Tragen. Diese Optiken können Ihre gewünschte Wirkung nur bei exakter Positionierung entfalten. Eine postoperative Feinpositionierung ist nicht möglich, was die Ansprüche an den Operateur bei Implantation der Linsen erhöht. Minimalinvasive microinzisionelle Operationstechniken bieten heute gute Möglichkeiten, die Implantate exakt zu positionieren. Neben den Dezentrierungen können Intraokularlinsen auch dislozieren, beispielweise durch intra- oder postoperative Kapselrupturen, Linsenverziehungen oder auch Rotation der Implantate. Hier ist ein weiterer chirurgischer Eingriff von Nöten. Der Vortrag stellt dementsprechend verschiedene Videos und praktische Hinweise zur Handhabung postoperativer Linsendislokationen vor.
Im Rahmen des Vortrags wird zunächst ein Überblick über die aktuell angewandten Linsensysteme in der (refraktiven) Kataraktchirurgie sowie im Rahmen des RLA gesprochen. Hierzu zählen die monofokalen sphärischen Standardlinsen, aber auch asphärische, torische und multifokale Implantate.
Speziell wird auf die Ergebnisse einer Studie zu einem neuen multifokalen-torischen Implantat eingegangen. Der Schwerpunkt des Vortrages liegt dann weiterhin auf den trifokalen Korrektionsmöglichkeiten. Zum einen wird die sog. binokulare Trifokalität, bei der zwei multifokale Intraokularlinsen unterschiedlicher Addition implantiert werden, besprochen. Durch die Anpassung jeweils eines Auges an den Intermediär- bzw. Nahbereich soll so bei verringerten optischen Phänomenen ein deutliches Sehen in drei Hauptdistanzen ermöglicht werden. Weiterhin befasst sich der Vortrag aber auch mit den neuen echten trifokalen Optiksystemen, welche ebenfalls deutliches Sehen in verschiedenen Entfernungen gewährleisten können.
Im dritten Teil des Vortrages werden aktuelle Langzeitergebnisse aus einer FDA Studie zur Evaluation einer kammerwinkelgestützten phaken Intraokularlinse, mit speziellem Augenmerk auf den cornealen Endothelzellverlust, sowie eine neuartige sulcusgestütze phake Intraokularlinse mit zentralem Loch zur Glaukomvermeidung vorgestellt.