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Advertising arbitrage
(2014)
Speculators often advertise arbitrage opportunities in order to persuade other investors and thus accelerate the correction of mispricing. We show that in order to minimize the risk and the cost of arbitrage an investor who identifies several mispriced assets optimally advertises only one of them, and overweights it in his portfolio; a risk-neutral arbitrageur invests only in this asset. The choice of the asset to be advertised depends not only on mispricing but also on its "advertisability" and accuracy of future news about it. When several arbitrageurs identify the same arbitrage opportunities, their decisions are strategic complements: they invest in the same asset and advertise it. Then, multiple equilibria may arise, some of which inefficient: arbitrageurs may correct small mispricings while failing to eliminate large ones. Finally, prices react more strongly to the ads of arbitrageurs with a successful track record, and reputation-building induces high-skill arbitrageurs to advertise more than others.
Im vorliegenden Beitrag werden die Ergebnisse der kontrastiven Forschung von phraseologischen Neologismen im Deutschen und Ukrainischen gezeigt. Das Ziel dieses Beitrags besteht darin, die phraseologischen Neologismen, die in der Corona-Pandemie in Deutschland und in der Ukraine in digitalen Medien verwendet wurden, zu analysieren, die strukturell-semantischen Merkmale ausgewählter phraseologischer Einheiten in beiden Sprachen zu beschreiben, ihre konzeptuelle Analyse durchzuführen, die vorhandenen Neologismenpaare einander gegenüberzustellen sowie Äquivalenztypen zu untersuchen. Die Materialbasis bilden diesbezüglich 96 deutsche und 60 ukrainische phraseologische Neologismen der Jahre 2020–2021.
NOSTRIN belongs to the recently defined F-BAR protein family. F-BAR proteins are
multi-domain proteins, which serve as adaptors between plasma membrane and
cytoskeleton components in processes such as membrane protrusion formation,
endocytosis and migration. NOSTRIN encompasses a F-BAR domain at the N-terminus,
which mediates membrane association, followed by a HR1 motif and an intermediate
domain (ID) domain in the middle, and a SH3 domain at the C-terminus. The domain
architecture and ability to form oligomers enable NOSTRIN to coordinate several
interaction partners namely dynamin, caveolin, N-WASP and endothelial nitric oxide
synthase (eNOS) in the process of eNOS trafficking. In this context NOSTRIN was
originally identified and hence termed eNOS traffick inducer. NOSTRIN is expressed in
vascularized tissues (e.g. liver and lung) and in primary endothelial cells.
Aims of the present work were (1) to investigate if NOSTRIN is involved in other
processes besides eNOS trafficking, (2) to analyse the function of NOSTRIN in vivo
through knockdown of NOSTRIN in developing zebrafish and (3) to study the
consequences of the loss of NOSTRIN on signal transduction in a primary cell culture
model derived from NOSTRIN knockout mice.
To study the possible involvement of NOSTRIN in other processes besides eNOS
trafficking a yeast two-hybrid screen was performed in which fibroblast growth factor
receptor 1 (FGFR1) was identified as a putative novel interaction partner of NOSTRIN. In
a series of yeast two-hybrid, pulldown and co-immunoprecipitation experiments the
interaction between NOSTRIN and FGFR1 was confirmed to occur between
endogenously expressed proteins and determined to be direct and to depend on the ID
domain of NOSTRIN and the 130 C-terminal amino acid residues of FGFR1. FGFR1 is
activated by binding of fibroblast growth factors (FGFs) and induces several different
signal transduction pathways (e.g. MAPK and Akt pathway). Overexpression of
NOSTRIN in HeLa cells specifically enhanced FGF2-dependent MAPK activation.
Accordingly, depletion of NOSTRIN attenuated FGF2-dependent MAPK activation and
did not affect FGF2-induced Akt activation.
In summary, NOSTRIN has been identified as a novel interaction partner of FGFR1
involved in FGF2-dependent signal transduction.
The morpholino oligonucleotide-mediated knockdown of NOSTRIN in developing
zebrafish caused vascular leakage and irregular vascular patterning e.g. a loss of the
proper trajectory of intersegmental vessel and interruptions of the dorsal longitudinal
anastomotic vessel. The vascular phenotype was consistent upon use of two different
morpholinos and could be rescued in a dose dependent manner by the injection of
zebrafish NOSTRIN mRNA. Detailed analysis involving confocal and time lapse
microscopy in zebrafish with endothelial specific expression of EGFP revealed that the
knockdown of NOSTRIN impacts in vivo on the migration and morphology of endothelial
tip cells and leads to a reduction of filopodia number and length.
Additionally a NOSTRIN knockout mouse was generated. The analysis of FGFR1 signal
transduction in primary mouse lung endothelial cells (MLECs) from NOSTRIN knockout
and wild type mice revealed that FGF2-dependent MAPK activation was attenuated in
MLECs isolated from NOSTRIN knockout mice when compared to MLECs isolated from
wild type mice. The effect of NOSTRIN on FGF2-dependent signal transduction seems to
be specific, since VEGF-induced MAPK activation was not affected in NOSTRIN
knockout MLECs. The importance of NOSTRIN for FGF2 signal transduction in vivo is
demonstrated by the greatly impaired angiogenic response to FGF2 in NOSTRIN
knockout mice in matrigel plug assay. In a detailed biochemical analysis it was
discovered that NOSTRIN interacts with the activated small GTPase Rac1 and that
overexpression of NOSTRIN enhances Rac1 activation. Furthermore, the interactions of
NOSTRIN with both Rac1 and its GEF Sos1 are required for NOSTRIN-mediated
activation of Rac1. In accordance, activation of Rac1 was not detected upon FGF2
stimulation in NOSTRIN knockout MLECs.
In conclusion, the present work describes a novel function of the F-BAR protein
NOSTRIN in FGFR1 signal transduction. Data presented in this work demonstrate that
NOSTRIN is required for the assembly of a complex consisting of FGFR1, Sos1 and
Rac1 and subsequently for the FGF2-dependent activation of Rac1 in endothelial cells.
U radu se preispituju granice frazema s obzirom na tvorenice kao frazemske sastavnice (krenulo je niz brdo (nizbrdo) što, ići na ruku (naruku) komu) ili samostalne jedinice (bogtepitaj, budibogsnama, kvragu) koje prema postojećoj frazemskoj definiciji ne ulaze u frazeološki fond. Posebna se pozornost poklanja frazemskim polusloženicama kao novoustanovljenoj skupini frazema prema frazemskome opsegu (amo-tamo, brže-bolje, danas-sutra, rak-rana, više-manje, zbrda-zdola). Istraživanje je utemeljeno na korpusu hrvatskih pravopisa od Partaša do Babića i Moguša, hrvatskim općim i frazeološkim rječnicima te elektroničkom korpusu Hrvatska jezična riznica Instituta za hrvatski jezik i jezikoslovlje.
Parni prijedlozi
(2007)
U ovome se članku analiziraju poredbeni frazemi jednoga hrvatskog čakavskog govora prikupljeni na terenskome dijalektološkom istraživanju i uspoređuju s poredbenim frazemima hrvatskoga standardnog jezika. Posebna se pozornost poklanja onim čakavskim frazemima koji imaju različitu sliku u pozadini frazema unutar istoga frazemskog koncepta i onima koji nemaju ekvivalenta u standardu.
U radu se račlanjuje odnos reda riječi i negacije u hrvatskome crkvenoslavenskome jeziku. Prvi se vid toga odnosa tiče položaja niječnih izraza ne, ni i bez. U zadanome korpusu oni stoje ispred, odnosno lijevo od jezične jedinice koju niječu. Jedinica ispred koje se niječni izraz nalazi nije nužno glagol, pa ni finitni glagolski oblik. Položaj niječnih izraza povezan je i s razlikom, odnosno s utvrđivanjem razlike između sastavničke negacije, kao negacije nepredikatne sastavnice, i rečenične negacije, negacije predikata. Konačno, o redu riječi ovisi hoće li se ili neće provesti niječno slaganje. U hrvatskome je crkvenoslavenskome jeziku provođenje niječnoga slaganja djelomično (ne i proizvoljno), a ovisi o tome na kojemu se mjestu u rečenici nalazi niječna zamjenica ili prilog.
This paper offers an overview of the presence of the german language and culture in Serbia. The focus lies on the region Vojvodina, as it has the greatest significance for the spread of the German language, culture and literature in Serbia, and there German as a foreign language is still strongly represented in schools. At the same time, it presents the status of the German teacher training in Serbia and discusses some perspectives in this domain.
Two main types of methods are used in gene therapy: integrating vectors and nuclease-based genome engineering. Nucleases are site-specific and are efficient for knock-outs, but inefficient at inserting long DNA sequences. Integrating vectors perform this task with high efficiency, but their insertion occurs at random genomic positions. This can result in transformation of target cells, which leads to severe adverse events in a gene therapy context. Thus, it is of great interest to develop novel genome engineering tools that combine the advantages of both technologies. The main focus of this thesis is on generating such a targetable integrating vector.
The integrating vector used in this project is the Sleeping Beauty (SB) transposon, a DNA transposon characterized by high activity across a wide range of cells. The SB transposase was combined with an RNA-guided Cas9 nuclease domain. This nuclease component was meant to direct transposase integration to specific targets defined by RNAs. The SB transposase was fused to cleavage-inactivated Cas9 (dCas9) to tether it to the target sites. In addition, adapter proteins consisting of dCas9 and domains non-covalently interacting with SB transposase or the SB transposon were generated. All constituent domains of these fusion proteins were tested in enzymatic assays and almost all enzymatic activities could be verified.
Combining the fusion protein dCas9-SB100X with a gRNA binding a sequence from the AluY repetitive element resulted in a weak, but statistically significant enrichment around sites bound by the gRNA. This enrichment was ca. 2-fold and occurred within a 300 bp window downstream of target sites, or within the AluY element.
Targeting with adapter proteins and targeting of other targets (L1 elements or single-copy targets) did not result in statistically significant effects. Single-copy targets tested included the HPRT gene and three specifically selected GSH targets that were known to be receptive to SB insertions. The combination with a more sequence-specific transposase mutant also failed to increase specificity to a level allowing targeting of single-copy loci. Genome-wide analysis of insertions however demonstrated, that dCas9-SB100X has a different insertion profile than SB100X, regardless of the gRNA used.
As low efficiency of retargeting is likely a consequence of the high background activity of the SB100X transposase in the fusion constructs, a SB mutant with reduced DNA affinity, SB(C42), was generated. For this mutant, transposition activity was partly dependent on a dCas9 domain being supplied with a multi-copy target gRNA, specifically a 2-fold increase in the presence of a AluY-directed gRNA. Whether using this mutant results in improved targeting remains to be determined.
In a side project, an attempt was made to direct SB insertions to ribosomal DNA by fusing the transposase to a nucleolar protein. This fusion transposase partially localized to nucleoli and insertions catalyzed by this transposase were found to be enriched in nucleolus organizer regions (NORs) and nucleolus-associated domains (NADs).
The aim of a second side project was increasing the ratio between homology-directed repair (HDR) and non-homologous end-joining (NHEJ) at Cas9-mediated double-strand breaks (DSBs). To achieve this, Cas9 was fused to DNA-interacting domains and corresponding binding sequences were fused to the homology donors. While an increased HDR/NHEJ ration could be observed for the fusion proteins, it was not dependent on the presence on the binding sequences in the donor molecules.
In an ideal world all investment products, including hedge funds, would be marketable to all investors. In this ideal world, all investors would fully understand the nature of the products and would be able to make an informed choice whether to invest. Of course the ideal world does not exist – the retail investment market is characterised by asymmetries of information. Product providers know most about the products on offer (or at least they should do). Investment advisers often know rather less than the provider but much more than their retail customers. Providers and intermediary advisers are understandably motivated by the desire to sell their products. There is therefore a risk that investment products will be mis-sold by investment advisers or mis-bought by ill-informed investors. This asymmetry of information is dealt with in most countries through regulation. However, the regulatory response in different countries is not necessarily the same. There are various ways in which protections can be applied and it is important to understand that the cultural background and regulatory histories of countries flavours the way regulation has developed. This means (as will be explained in greater detail later) that some countries are better able than others to admit hedge funds to the retail sector. Following this Introduction, Section II looks at some key background issues. Section III then looks at some important questions raised by the retail hedge fund issue. Many of these are questions of balance. Balance lies at the heart of regulation of course – regulation must always balance the needs of investors and with market efficiency. Understanding the “retail hedge fund” question requires particular attention to balance. Section IV then looks at the UK regime and how the FSA has answered the balance question. Section V offers some international perspectives. Section VI concludes. It will be seen that there is no obviously right answer to the question whether hedge fund products should be marketed to retail investors. Each regulator in each jurisdiction needs to make up its own mind on how to deal with the various issues and balances. It is evident, however, that internationally there is a move towards a greater variety of retail funds. There is nothing wrong with that, provided the regulators and the retail customers they protect, understand sufficiently what sort of protection is, or is not, being offered in the regulatory regime.
This Paper will look at the changing nature of asset management, and will examine the nature of the European framework for collective investment undertakings, enshrined in the UCITS Directive2 in that light. This question whether the UCITS Directive in its current form remains an appropriate European response to the changing investment management landscape is an issue with which the European Commission is actively engaging through its Green Paper on the Enhancement of the EU Framework for Investment Funds, published in July 2005.3 But before considering these important questions, it is necessary to begin with an idea of what a collective investment, more specifically a UCITS actually is and how it fits conceptually in the broader world of pooled investments.....
Aufgrund der starken Heterogenität und Komplexität der akuten myeloischen Leukämie ist diese bis heute nicht zufriedenstellend zu behandeln. Die bestmögliche Therapie wird mittlerweile zunehmend auf die Erkrankung des Einzelnen angepasst. Vermehrt gewinnen Tyrosinkinase-Inhibitoren in der Therapie an Bedeutung. Diese Inhibitoren hemmen Proteine auf zellulärer Ebene.
Bei etwa 30% der AML-Patienten lassen sich Mutationen des FLT3-Gens nachweisen. Das Gen kodiert für die fms like tyrosine kinase 3, eine Rezeptor-Tyrosinkinase an der Zelloberfläche von unreifen Blutzellen des Knochenmarks. Durch Mutationen des FLT3 Gens erhalten diese Zellen einen Proliferationsvorteil gegenüber den physiologischen Blutzellen.
Am häufigsten kommt es zu in frame-Insertionen des FLT3-Gens, vor allem im Bereich der juxtamembranen Domäne: sogenannte interne Tandemduplikationen (ITD). Weiterhin kommen zu einem geringeren Teil Punktmutationen einzelner Codons, zum Beispiel im Bereich des activation loops oder im Bereich des gatekeepers vor. Durch das Auftreten der Punktmutationen, die entweder bereits zum Zeitpunkt der Diagnose vorliegen oder erst während einer Therapie mit einem Tyrosinkinase-Inhibitor entstehen können, verändert sich das Bindungsverhalten vieler solcher gegen FLT3 gerichteten Inhibitoren. Durch Letzteres kann ein mögliches Therapieversagen beispielsweise während der Behandlung mit AC220 (Quizartinib) erklärt werden (Smith et al.).
In der vorliegenden Dissertationsschrift sind Unterschiede der Signalwege zwischen FLT3-ITD und FLT3-ITD mit der zusätzlichen gatekeeper-Punktmutation F691L herausgearbeitet. Dafür wurden die beiden FLT3-Mutationen in den Vektor pMy-IRES-GFP eingebracht und retroviral in Ba/F3-Zellen transduziert. Nach Überprüfung der Expression von FLT3 ITD und dem Wachstumsverhalten unter Zugabe von AC220 (Quizartinib), wurden verschiedene Signalkaskaden von FLT3 mittels Western Blot untersucht. Hierbei zeigten sich sowohl Unterschiede für die Expression von phosphoryliertem ERK als auch von phosphoryliertem STAT5.
Durch verschieden starke Expressionen der FLT3130kDa- und FLT3160kDA-Varianten wurde eine unterschiedliche Lokalisation von FLT3-ITD in Zellen mit und ohne die Mutation F691L postuliert. Allerdings ließ sich diese experimentell mittels Immunfluoreszenz nicht belegen, da die Methode für die verwendeten Suspensionszellen nicht ausreichend geeignet war.
In den durchgeführten Versuchen zum Wachstumsverhalten der Zellen bei der Verwendung von Kinaseinhibitoren konnte bei der Verwendung des SYK-Inhibitors R406 eine dosisabhängige Proliferationshemmung der FLT3-ITD-mutierten Ba/F3- und 32D-Zellen beobachtet werden. Die Hemmung von FLT3 durch R406 wurde in der Literatur bereits beschrieben (Braselmann et al.).
Die abschließenden Experimente der Massenspektrometrie mit SILAC Markierung lassen mit der Detektion von mehreren hundert signifikant regulierten phosphorylierten Proteinen in den beiden FLT3-ITD-exprimierenden Populationen auf die Aktivierung unterschiedlicher Signalwege schließen. Durch das Vergleichen einzelner Teilexperimente ergaben sich Proteine, deren Phosphorylierung mehrfach in die gleiche Richtung reguliert war. Für Zellen, die zusätzlich zur ITD-Mutation die Mutation F691L besaßen, konnten insgesamt sieben hoch-regulierte, phosphorylierte Proteine ermittelt werden, bei denen ein zellulärer Effekt durch die Phosphorylierung der entsprechenden Aminosäurereste in der Literatur beschrieben ist.
Das im Western Blot nachgewiesene, in Zellen mit der Mutation F691L stärker phosphorylierte STAT5 ist aller Voraussicht nach Ursache der nachgewiesenen verstärkten Phosphorylierung von RPS6 im Experiment der globalen Phosphorylierung. Die PIM-Kinasen als Substrate einer STAT5-induzierten Transkription phosphorylieren RPS6 an Serin 235. Dies führt seinerseits zu einer verstärkten Translation von mRNA weiterer Gene. Die genauen Zusammenhänge der hier ermittelten Unterschiede müssen jedoch weiter untersucht werden.
In Zukunft könnte zudem die Untersuchung der beiden Proteine SHP 1 oder HSP90 weitere Aufschlüsse über die unterschiedlichen Signalwege geben. Für beide Proteine wurden Phosphorylierungen detektiert, die in den untersuchten Zellen mit FLT3-ITD bzw. der zusätzlichen Punktmutation F691L unterschiedlich reguliert sind.
Rhodopsins are the most universal biological light-energy transducers and abundant phototrophic mechanisms that evolved on Earth and have a remarkable diversity and potential for biotechnological applications. Recently, the first sodium-pumping rhodopsin KR2 from Krokinobacter eikastus was discovered and characterized. However, the existing structures of KR2 are contradictory, and the mechanism of Na+ pumping is not yet understood. Here, we present a structure of the cationic (non H+) light-driven pump at physiological pH in its pentameric form. We also present 13 atomic structures and functional data on the KR2 and its mutants, including potassium pumps, which show that oligomerization of the microbial rhodopsin is obligatory for its biological function. The studies reveal the structure of KR2 at nonphysiological low pH where it acts as a proton pump. The structure provides new insights into the mechanisms of microbial rhodopsins and opens the way to a rational design of novel cation pumps for optogenetics.
One of the aims of the SPARC collaboration [1] at FAIR is to perform precision atomic physics expe- riments with highly charged heavy ions at the High Energy Storage Ring (HESR). An internal target is indis- pensably an integral part for many such experiments. Ions with different charge states, which are obtained as a result of interaction of an ion beam with the target, need to be effectively separated and detected. In this work we present ion optical studies unambiguously showing the feasibility of SPARC experiments at the HESR.
Se discute aquí la reseña de Friedrich Blanckenburg sobre "Las penas del joven Werther" (1774) de J. W. Goethe. La reseña, de la que ofrecemos la traducción al español de varios pasajes, fue publicada unos meses más tarde que la polémica y revolucionaria novela de Goethe y constituye un documento valioso no solo de su recepción, sino también de la teorización acerca del género en el contexto de finales de la Segunda Ilustración en Alemania. Da cuenta, en efecto, de un rasgo central de este periodo: la recepción sensibilista, 'empfindsam', que tendría un efecto benefactor sobre la sociabilidad y las costumbres. Además, en una relación en cierto modo ambigua con este llamado a la empatía socialmente útil del crítico y del lector, el autor presenta elementos que señalan llamativamente hacia una doctrina de la autonomía de la esfera estética. Lo que queda sin saberse es si se trata de una "desprolijidad" de la reseña o de una lúcida interpretación de la "voz doble" que plantea Goethe en su famosa novela epistolar.
"Österreich - USA: Künstlerischer und interkultureller Dialog". Konferenz der Austrian Studies Association (ASA) an der Universität Wien, 14.-17. März 2016
Zum zweiten Mal seit Bestehen der 1961 ins Leben gerufenen Austrian Studies Association (ASA) fand die jährliche ASA-Konferenz in Europa, und zwar wieder in Wien, statt. Organisiert wurde sie von Pia Janke (Forschungsplattform Elfriede Jelinek, Universität Wien), Maria-Regina Kecht (Rice University) und Teresa Kovacs (Forschungsplattform Elfriede Jelinek, Universität Wien). Die Veranstaltung vernetzte durch ein vielfältiges Programm an wissenschaftlichen Vorträgen und künstlerischen Programmpunkten die Universität Wien mit anderen in Wien beheimateten Institutionen, die als Kooperationspartner fungierten, namentlich mit dem Wien Museum, dem Österreichischen Filmmuseum und dem Amerika-Haus.
"… die ehernen Blöcke männlichen Schaffens umkreisen" - Elfriede Jelinek queert Lessing und Goethe
(2016)
Der Beitrag verschränkt kommunikations-, informations-, kulturwissenschaftliche sowie philosophische Ansätze zur Störung mit gender- und queer theory, um Elfriede Jelineks 'Gattung' des Sekundärdramas analytisch zu beschreiben. Jelinek verfasst ihre Sekundärdramen zu kanonisierten Dramen des deutschsprachigen Raums und stellt über ihr typisches, intertextuelles Verfahren Bezug zu den Stücken her, fordert gleichzeitig aber auch die Kombination der Sekundärdramen mit ihren Bezugstexten im Moment der Inszenierung und geht damit über ihr bisheriges Verfahren hinaus. Ausgehend von der Feststellung, dass Jelineks Sekundärdramen in den Umsetzungen am Theater meist als weibliche Gegenschreibung interpretiert werden, will der vorliegende Beitrag zeigen, dass die Sekundärdramen vielmehr an einer Auflösung der Kategorien von 'Weiblichkeit' und 'Männlichkeit' arbeiten. Ein besonderes Augenmerk liegt dabei auf der Thematisierung des Inzests, der mit Judith Butler als vorhandene Ordnungen und Relationen verschiebendes Element gelesen werden kann.