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Der viel diskutierte Begriff der "Multinormativität" steht heute in Konkurrenz zu dem des "Rechtspluralismus" und der "Diversität" des Rechts. Alle drei Begriffe verfügen nicht über eine inhaltliche und funktionale Eindeutigkeit und zeigen kein bestimmtes Verhältnis zu- und untereinander. Eine sehr vage Gemeinsamkeit solcher "Rechtspluralitäten" besteht allein in deren Unterscheidung oder Abweichung vom Gegenbegriff einer "Rechtseinheit" bzw. der ideal gedachten Einheit der Rechtsordnung, wie sie von den Kodifikatoren des Privatrechts im Zeitalter der Aufklärung versucht wurde zu verwirklichen. In einem solchen Spannungsverhältnis zwischen Einheitlichkeit oder Vielfalt gesellschaftlicher und staatlicher Rechtsgestaltung steht jedes organisierte Gemeinwesen. Das ist eine historische Erfahrung, die sich seit der römischen Antike in der rechtssystematischen Einteilung in ein "ius universale " und "ius speciale/particulare" zeigt. In der aktuellen Diskussion scheint "Multinormativität" als der umfassendere Begriff für die Rechtevielfalt gebraucht zu werden. In der rechtstheoretisch orientierten Literatur kann man je nach disziplinärer Einteilung bis zu sieben "Rechtspluralismen" unterscheiden, die die Definitionsnot und sprachliche Bedeutungsvielfalt nachdrücklich belegen. Dieser "Pluralismus" kann durch Rechte oder auch "Rechts-Ordnungen" in der Interaktion zwischen einer herrschenden und einer alternativen "Rechts-Ordnung" bestimmt sein. Die Konkretisierungsbedürftigkeit von "Rechtspluralismus" und "Multinormativität" haben diese beiden Begriffe auch gemeinsam mit dem geläufigen Nachbarbegriff der pluralen "Rechtsquellen", die als Sammelbezeichnung für die Grundlagen rechtlicher Entscheidungen fungieren. Multinormativität kann heute als eine extensive Variante von "Rechtsquellenvielfalt" oder "Rechtsvielfalt" gesehen werden, beschränkt sich jedoch nicht auf die Dimension der rechtlichen Entscheidungsgrundlagen, sondern erweitert diese auch auf die Vielzahl möglicher außerrechtlicher entscheidungsrelevanter "Normen". Das ist der Grund, weshalb heute der Begriff des "normative pluralism" dem des "legal pluralism" vorgezogen wird, um auch das "phenomenon of law beyond the state" in den Griff zu bekommen. In der deutschen Literatur ist heute das beliebte Bild und der vielgebrauchte Begriff der "Rechtsquellen" höchst umstritten, da in ihm mehr das "fließende" Element höchst mobiler rechtlicher Ordnungsinstrumente zum Ausdruck kommt als die Bestimmtheit und Sicherheit rechtlicher Normangebote. Luhmann bezeichnete die eine Rechtspluralität indizierende Rechtsquellenlehre als ein "mehrschichtiges Theoriegebäude mit schwankenden Fundamenten" und Esser sprach sogar von den "doktrinären Peinlichkeiten", vor die sich die Rechtsquellenlehre gestellt sah und gestellt sieht. Multinormativität löst heute weitgehend den "Rechtsquellen"-Begriff ab, indem er ihn vor dem Hintergrund internationaler politischer Praxis und Erfahrungen überlagert und ausweitet. ...
The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression but is currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
The challenges posed by climate and land use change are increasingly complex, with ever-increasing and accelerating impacts on the global environmental system. The establishment of an internationally harmonized, integrated, and long-term operated environmental monitoring infrastructure is one of the major challenges of modern environmental research. Increased efforts are currently being made in Europe to establish such a harmonized pan-European observation infrastructure, and the European network of Long-Term Ecological Research sites – LTER-Europe – is of particular importance. By evaluating 477 formally accredited LTER-Europe sites, this study gives an overview of the current distribution of these infrastructures and the present condition of long-term environmental research in Europe. We compiled information on long-term biotic and abiotic observations and measurements and examined the representativeness in terms of continental biogeographical and socio-ecological gradients. The results were used to identify gaps in both measurements and coverage of the aforementioned gradients. Furthermore, an overview of the current state of the LTER-Europe observation strategies is given. The latter forms the basis for investigating the comparability of existing LTER-Europe monitoring concepts both in terms of observational design as well as in terms of the scope of the environmental compartments, variables and properties covered.
In diesem Beitrag wird korpusbasiert, qualitativ und aus kontrastiver Sicht anhand ausgewählter Einzelbeispiele untersucht, welchen Beitrag die Frame-Semantik bei der Analyse konzeptueller Metaphern im aktuellen Migrationsdiskurs in der deutschen und italienischen Presse leisten kann. Sie macht es möglich, unterschiedliche Perspektivierungen bei der Betrachtung des Phänomens herauszukristallisieren, da semantische Frames ein facettenreiches Angebot für den Blickwinkel der Betrachtung bereitstellen. Auch Metaphern selbst besitzen diese Eigenschaft der Perspektivierung, vor allem auch solche, die charakteristisch für einen kulturspezifischen Kontext stehen. Zu den Möglichkeiten, die der Einsatz von Metaphern bietet, zählt vor allem der "Highlighting und Hiding"-Effekt (LAKOFF/JOHNSON 1980), indem Metaphern bestimmte Aspekte betonen oder verdunkeln. Um welche es sich dabei im Einzelnen handelt, hängt von mehreren Faktoren ab, wie zum Beispiel der politischen Orientierung von Journalisten oder Politikern oder der wirtschaftlichen Lage eines Landes.
In all eukaryotic cells, the nucleolus is functionally and structurally linked to rRNA synthesis and ribosome biogenesis. This compartment contains as well factors involved in other cellular activities, but the functional interconnection between non-ribosomal activities and the nucleolus (structure and function) still remains an open question. Here, we report a novel mass spectrometry analysis of isolated nucleoli from Arabidopsis thaliana plants using the FANoS (Fluorescence Assisted Nucleolus Sorting) strategy. We identified many ribosome biogenesis factors (RBF) and proteins non-related with ribosome biogenesis, in agreement with the recognized multi-functionality of the nucleolus. Interestingly, we found that 26S proteasome subunits localize in the nucleolus and demonstrated that proteasome activity and nucleolus organization are intimately linked to each other. Proteasome subunits form discrete foci in the disorganized nucleolus of nuc1.2 plants. Nuc1.2 protein extracts display reduced proteasome activity in vitro compared to WT protein extracts. Remarkably, proteasome activity in nuc1.2 is similar to proteasome activity in WT plants treated with proteasome inhibitors (MG132 or ALLN). Finally, we show that MG132 treatment induces disruption of nucleolar structures in WT but not in nuc1.2 plants. Altogether, our data suggest a functional interconnection between nucleolus structure and proteasome activity.
O intuito deste trabalho é destacar a importância do escrito juvenil Traumland para a formação do poeta Georg Trakl, por meio de uma leitura cerrada do texto. Sob a forma de uma lembrança do narrador, esse breve relato apresenta uma experiência de iniciação ou perda da inocência oriunda da percepção do mal no mundo, concentrado na figura de uma prima doente, Maria. O conflito entre o anseio romântico (Sehnsucht) pleno de expectativas e entusiasmo e essa realidade aterradora, vivenciado como uma quebra no sentimento (Stimmung) de harmonia cósmica, impulsiona uma transformação no sentimento e na visão de mundo do protagonista, que metaforicamente pode ser lida como a transição de uma poética puramente romântica para uma poética mais sintonizada com as exigências do século XX, especialmente no sentido da dimensão reconhecida ao mal irremediável, que não pode ser completamente romantizado.
Kaum eine geistes- und kulturwissenschaftliche Disziplin hat in Italien in solchem Ausmaß unter Selbstdarstellungs- und Rechtfertigungszwang gestanden und sich über so heftige Widerstände hinwegsetzen müssen wie die Komparatistik. Ein Leserbrief des Literaturwissenschaftlers Armando Gnisci, der in den 1980er- und 1990er-Jahren die Szene der italienischen Komparatistik wesentlich geprägt, aber nur marginal bis ins neue Jahrtausend mitbestimmen konnte, gibt einen konzis-kritischen – wenn auch leicht polemischen – Einblick in das, was seit dem letzten state of the art aus dem Jahre 1991 auf dem Gebiet der Allgemeinen und Vergleichenden Literaturwissenschaft in Italien passiert ist. Entlang dieser Linie verlief nämlich die wichtigste Front im Streit zwischen den Nationalphilologen und den Komparatisten. Gniscis Schreiben mit dem programmatischen wie suggestiven Titel "Comparatisti e italianisti, le due tribù" [Komparatisten und Italianisten, die beiden Stämme] – erschienen am 21. März 2004 in der Kulturbeilage Domenica – ist ein Rundumschlag gegen die seinerzeit in Italien weitverbreitete Ansicht, die Allgemeine und Vergleichende Literaturwissenschaft als "sub-category of Italian literature departments" zu betrachten.
We study platform design in online markets in which buying involves a (nonmonetary) cost for consumers caused by privacy and security concerns. Firms decide whether to require registration at their website before consumers learn relevant product information. We derive conditions under which a monopoly seller benefits from ex ante registration requirements and demonstrate that the profitability of registration requirements is increased when taking into account the prospect of future purchases or an informational value of consumer registration to the firm. Moreover, we consider the effectiveness of discounts (store credit) as a means to influence the consumers’ registration decision. Finally, we confirm the profitability of ex ante registration requirements in the presence of price competition.
We study the effect of the chiral symmetry restoration (CSR) on heavy-ion collisions observables in the energy range sNN=3–20GeV within the Parton-Hadron-String Dynamics (PHSD) transport approach. The PHSD includes the deconfinement phase transition as well as essential aspects of CSR in the dense and hot hadronic medium, which are incorporated in the Schwinger mechanism for particle production. Our systematic studies show that chiral symmetry restoration plays a crucial role in the description of heavy-ion collisions at sNN=3–20GeV, realizing an increase of the hadronic particle production in the strangeness sector with respect to the non-strange one. Our results provide a microscopic explanation for the horn structure in the excitation function of the K+/π+ ratio: the CSR in the hadronic phase produces the steep increase of this particle ratio up to sNN≈7GeV, while the drop at higher energies is associated to the appearance of a deconfined partonic medium. Furthermore, the appearance/disappearance of the horn structure is investigated as a function of the system size. We additionally present an analysis of strangeness production in the (T,μB)-plane (as extracted from the PHSD for central Au+Au collisions) and discuss the perspectives to identify a possible critical point in the phase diagram.
Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIα were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution.
The paper presents the possibilities for analyzing deverbal derivatives from verbs ending in -ier(en); in many cases these exist as doublets, with the suffix -ung and/or the suffix -(at)ion. Based on selected examples of these doublets, the paper demonstrates how both monolingual and bilingual dictionaries fail to take sufficient account of the semantic differences between such competing forms. The author also presents research questions connected with this issue, and outlines a methodology for addressing these questions based on metalexicographic and corpus analysis; this methodology is demonstrated using the example of the doublet Diskrimination and Diskriminierung
We have determined the crystal structures of two decachlorocyclopentasilanes, namely bis(tetra-n-butylammonium) dichloride decachlorocyclopentasilane dichloromethane disolvate, 2C16H36N+·2Cl−·Si5Cl10·2CH2Cl2, (I), and bis(tetraethylammonium) dichloride decachlorocyclopentasilane dichloromethane disolvate, 2C8H20N+·2Cl−·Si5Cl10·2CH2Cl2, (II), both of which crystallize with discrete cations, anions, and solvent molecules. In (I), the complete decachlorocyclopentasilane ring is generated by a crystallographic twofold rotation axis. In (II), one cation is located on a general position and the other two are disordered about centres of inversion. These are the first structures featuring the structural motif of a five-membered cyclopentasilane ring coordinated from both sides by a chloride ion. The extended structures of (I) and (II) feature numerous C—H⋯Cl interactions. In (II), the N atoms are located on centres of inversion and as a result, the ethylene chains are disordered over equally occupied orientations.
Rho GTPases control fundamental cellular processes and Cdc42 is a well-studied member of the family that controls filopodia formation and cell migration. Although the regulation of Cdc42 activity by nucleotide binding is well documented, the mechanisms driving its proteostasis are not clear. Here, we demonstrate that the highly conserved, RING domain containing E3 ubiquitin ligase XIAP controls the protein stability of Cdc42. XIAP binds to Cdc42 and directly conjugates poly ubiquitin chains to the Lysine 166 of Cdc42 targeting it for proteasomal degradation. Depletion of XIAP led to an increased protein stability and activity of Cdc42 in normal and tumor cells. Consistently, loss of XIAP enhances filopodia formation in a Cdc42-dependent manner and this phenomenon phenocopies EGF stimulation. Further, XIAP depletion promotes lung colonization of tumor cells in mice in a Cdc42-dependent manner. These observations shed molecular insights into ubiquitin-dependent regulation of Cdc42 and that of actin cytoskeleton.
The value of plant ecological datasets with hundreds or thousands of species is principally determined by the taxonomic accuracy of their plant names. However, combining existing lists of species to assemble a harmonized dataset that is clean of taxonomic errors can be a difficult task for non-taxonomists. Here, we describe the range of taxonomic difficulties likely to be encountered during dataset assembly and present an easy-to-use taxonomic cleaning protocol aimed at assisting researchers not familiar with the finer details of taxonomic cleaning. The protocol produces a final dataset (FD) linked to a companion dataset (CD), providing clear details of the path from existing lists to the FD taken by each cleaned taxon. Taxa are checked off against ten categories in the CD that succinctly summarize all taxonomic modifications required. Two older, publicly-available lists of naturalized Asteraceae in Australia were merged into a harmonized dataset as a case study to quantify the impacts of ignoring the critical process of taxonomic cleaning in invasion ecology. Our FD of naturalized Asteraceae contained 257 species and infra-species. Without implementation of the full cleaning protocol, the dataset would have contained 328 taxa, a 28% overestimate of taxon richness by 71 taxa. Our naturalized Asteraceae CD described the exclusion of 88 names due to nomenclatural issues (e.g. synonymy), the inclusion of 26 updated currently accepted names and four taxa newly naturalized since the production of the source datasets, and the exclusion of 13 taxa that were either found not to be in Australia or were in fact doubtfully naturalized. This study also supports the notion that automated processes alone will not be enough to ensure taxonomically clean datasets, and that manual scrutiny of data is essential. In the long term, this will best be supported by increased investment in taxonomy and botany in university curricula.
Erasmus of Rotterdam was a scholar with a broad range of interests living in the Renaissance and Reformation period, and he has become the eponymous figurehead of a European university mobility programme initiated thirty years ago. With reference to the partnership between the University of Ostrava (Czech Republic) and the Zittau/Görlitz University of Applied Sciences (Germany), this paper demonstrates the key importance of this programme for university courses in translation studies, showing how the programme is implemented in line with Erasmus of Rotterdam's ideas and convictions.
OBJECTIVE: The role of supraglottic airway devices in emergency airway management is highlighted in international airway management guidelines. We evaluated the application of the new generation laryngeal tube suction (LTS-II/LTS-D) in the management of in-hospital unexpected difficult airway and cardiopulmonary resuscitation.
METHODS: During a seven-year period, patients treated with a laryngeal tube who received routine anesthesia and had an unexpected difficult airway (Cormack Lehane Grade 3-4), who underwent cardiopulmonary resuscitation, or who underwent cardiopulmonary resuscitation outside the operating room and had a difficult airway were evaluated. Successful placement of the LTS II/LTS-D, sufficient ventilation, time to placement, number of placement attempts, stomach content, peripheral oxygen saturation/end-tidal carbon dioxide development (SpO2/etCO2) over 5 minutes, subjective overall assessment and complications were recorded.
RESULTS: In total, 106 adult patients were treated using an LTS-II/LTS-D. The main indication for placement was a difficult airway (75%, n=80), followed by cardiopulmonary resuscitation (25%, n=26) or an overlap between both (18%, n=19). In 94% of patients (n=100), users placed the laryngeal tube during the first attempt. In 93% of patients (n=98), the tube was placed within 30 seconds. A significant increase in SpO2 from 97% (0-100) to 99% (5-100) was observed in the whole population and in cardiopulmonary resuscitation patients. The average initial etCO2 of 39.5 mmHg (0-100 mmHg) decreased significantly to an average of 38.4 mmHg (10-62 mmHg) after 5 minutes. A comparison of cardiopulmonary resuscitation patients with non-cardiopulmonary resuscitation patients regarding gastric contents showed no significant difference.
CONCLUSIONS: LTS-D/LTS-II use for in-hospital unexpected difficult airway management provides a secure method for primary airway management until other options such as video laryngoscopy or fiber optic intubation become available.
Mutualistic interactions between plants and animals can affect both plant and animal communities, and potentially leave imprints on plant demography. Yet, no study has simultaneously tested how trait variation in plant resources shapes the diversity of animal consumers, and how these interactions influence seedling recruitment. Here, we analyzed whether (i) phylogenetic diversity and functional diversity of fruiting plants were correlated with the corresponding diversity of frugivorous birds, and (ii) whether phylogenetic diversity and functional identity of plant and bird communities influenced the corresponding diversity and identity of seedling communities. We recorded mutualistic interactions between fleshy-fruited plants and frugivorous birds and seedling communities in 10 plots along an elevational gradient in the Colombian Andes. We built a phylogeny for plants/seedlings and birds and measured relevant morphological plant and bird traits that influence plant-bird interactions and seedling recruitment. We found that phylogenetic diversity and functional diversity of frugivorous birds were positively associated with the corresponding diversities of fruiting plants, consistent with a bottom-up effect of plants on birds. Moreover, the phylogenetic diversity of seedlings was related to the phylogenetic diversity of plants, but was unrelated to the phylogenetic diversity of frugivorous birds, suggesting that top-down effects of animals on seedlings were weak. Mean seed mass of seedling communities was positively associated with the mean fruit mass of plants, but was not associated with the mean avian body mass in the frugivore communities. Our study shows that variation in the traits of fleshy-fruited plants was associated with the diversity of frugivorous birds and affected the future trajectory of seedling recruitment, whereas the morphological traits of animal seed dispersers were unrelated to the phylogenetic and functional structure of seedling communities. These findings suggest that bottom-up effects are more important than top-down effects for seed-dispersal interactions and seedling recruitment in diverse tropical communities.
Bestimmung des klinischen Nutzens systemischer adjuvanter Therapien beim frühen Mammakarzinom
(2017)
Die onkologische Therapie befindet sich im Umbruch. Hohe Erwartungen sind mit einer Reihe innovativer zielgerichteter Medikamente verknüpft, die sich derzeit in der klinischen Entwicklung befinden. Vor diesem Hintergrund erfahren Diskussionen um die Begriffe klinischer Nutzen oder klinische Relevanz neue Aktualität. Dies gilt auch für die Weiterentwicklungen der adjuvanten systemischen Therapie des frühen Mammakarzinoms. In Anbetracht der kurativen Zielsetzung erfolgt die Beurteilung des klinischen Nutzens einer adjuvanten Therapie maßgeblich anhand von Wirksamkeitsendpunkten. Der Fokus liegt hierbei auf Verbesserungen des krankheitsfreien Überlebens und des Rezidivrisikos. Eine Aussage zum Gesamtüberleben ist aufgrund der heute erreichten niedrigen Mortalitätsraten erst nach sehr langen Beobachtungszeiten möglich. Folgerichtig sollte neuen Medikamenten für die adjuvante Therapie ein klinischer Nutzen zugesprochen werden, wenn sie eine weitere Reduktion des Rezidivrisikos über den heutigen hohen Standard hinaus ermöglichen. Die Evidenz für etablierte adjuvante Therapiestandards beim frühen Mammakarzinom kann als objektiver Maßstab zum Vergleich herangezogen werden. Am Beispiel der adjuvanten endokrinen Therapie, der adjuvanten Polychemotherapie und der adjuvanten Anti-HER2-Therapie werden in diesem Übersichtsartikel die Anforderungen für den klinischen Nutzen neuer adjuvanter Therapien beim frühen Mammakarzinom abgeleitet.