Refine
Year of publication
- 2019 (3302) (remove)
Document Type
- Article (1600)
- Part of Periodical (396)
- Book (265)
- Doctoral Thesis (211)
- Contribution to a Periodical (195)
- Part of a Book (182)
- Preprint (164)
- Review (141)
- Working Paper (96)
- Conference Proceeding (35)
Language
- English (1831)
- German (1308)
- Portuguese (67)
- French (31)
- Multiple languages (23)
- Turkish (16)
- Spanish (15)
- Italian (5)
- Ukrainian (4)
- mis (2)
Has Fulltext
- yes (3302) (remove)
Is part of the Bibliography
- no (3302)
Keywords
- Literatur (69)
- Deutsch (61)
- taxonomy (60)
- Experiment (47)
- Sprache (33)
- new species (32)
- Literarisches Experiment (30)
- Deutsch als Fremdsprache (27)
- Geschichte (25)
- Digitalisierung (23)
Institute
- Medizin (574)
- Präsidium (346)
- Physik (295)
- Frankfurt Institute for Advanced Studies (FIAS) (189)
- Informatik (159)
- Wirtschaftswissenschaften (144)
- Biowissenschaften (117)
- Sustainable Architecture for Finance in Europe (SAFE) (106)
- Gesellschaftswissenschaften (104)
- Neuere Philologien (90)
Warum versucht sich ein zu diesem Zeitpunkt berühmter Gelehrter wie Georg Simmel, der ja 1900 "Philosophie des Geldes" publiziert, in der Dichtung? Ganz unabhängig von seinem Scheitern in diesem Fach möchte ich im Folgenden diese Frage ausweiten und in den Kontext einer umfassenderen Beobachtung stellen. Nämlich der, dass sich im Laufe der langen Jahrhundertwende Texte herausbilden, die in ihrer Form einmalig oder zumindest besonders sind und zu denen auch viele Arbeiten von Georg Simmel gehören – nicht nur die, die er als Momentbilder publiziert. In einem ersten Schritt werde ich diese neuen Texte der langen Jahrhundertwende beschreiben, um im Anschluss Überlegungen dazu anzustellen, welche Bedingungen diese Formen begünstigt haben. Abschließend wende ich mich kurz einem Vergleich von Simmel und Benjamin zu, um auf diese Weise aufzuzeigen, dass für diese Texte die Formation mehr ist als nur Grundlage für die Vermittlung von Konzepten und selbst eine konzeptuelle Funktion übernehmen soll. Daher ist es hilfreich, die jeweils formalen Strukturen und Modi genauer unter die Lupe zu nehmen. Ich werde mich Simmel also nicht aus der Perspektive der Soziologie oder Kunstphilosophie nähern, sondern aus der einer kulturwissenschaftlichen Literaturwissenschaft.
We analyze cyclical co-movement in credit, house prices, equity prices, and longterm interest rates across 17 advanced economies. Using a time-varying multi-level dynamic factor model and more than 130 years of data, we analyze the dynamics of co-movement at different levels of aggregation and compare recent developments to earlier episodes such as the early era of financial globalization from 1880 to 1913 and the Great Depression. We find that joint global dynamics across various financial quantities and prices as well as variable-specific global co-movements are important to explain fluctuations in the data. From a historical perspective, global co-movement in financial variables is not a new phenomenon, but its importance has increased for some variables since the 1980s. For equity prices, global cycles play currently a historically unprecedented role, explaining more than half of the fluctuations in the data. Global cycles in credit and housing have become much more pronounced and longer, but their importance in explaining dynamics has only increased for some economies including the US, the UK and Nordic European countries. We also include GDP in the analysis and find an increasing role for a global business cycle.
We propose a simple modification of the time series filter by Hamilton (2018) that yields reliable and economically meaningful real-time output gap estimates. The original filter relies on 8-quarter-ahead forecast errors of a simple autoregression of log real GDP. While this approach yields a cyclical component of GDP that is hardly revised with new incoming data due to the one-sided filtering approach, it does not cover typical business cycle frequencies evenly, but short business cycles are muted and medium length business cycles are amplified. Further, the estimated trend is as volatile as GDP itself and can thus hardly be interpreted as potential GDP. A simple modification that is based on the mean of 4- to 12-quarter-ahead forecast errors shares the favorable real-time properties of the Hamilton filter, but leads to a much better coverage of typical business cycle frequencies and a smooth estimated trend. Based on output growth and inflation forecasts and a comparison to revised output gap estimates from policy institutions, we find that real-time output gaps based on the modified Hamilton filter are economically much more meaningful measures of the business cycle than those based on other simple statistical trend-cycle decomposition techniques such as the HP or the Bandpass filter.
Introduction: The Retro-IDEAL (ILUVIEN Implant for chronic DiabEtic MAcuLar edema) study is a retrospective study designed to assess real-world outcomes achieved with the ILUVIEN® (0.19 mg fluocinolone acetonide (FAc)) in patients with chronic diabetic macular edema (DME) in clinical practices in Germany.
Methods: This study was conducted across 16 sites in Germany and involved 81 eyes (63 patients) with persistent or recurrent DME and a prior suboptimal response to a first-line intravitreal therapy (primarily anti-VEGF intravitreal therapies).
Results: Patients were followed-up for 30.8 ± 11.3 months (mean ± standard deviation) and had a mean age of 68.0 ± 10.4 years. Best-recorded visual acuity (BRVA) improved by +5.5 letters at month 9 (P ⩽ 0.005, n=56; from a baseline of 49 letters) and this was maintained through to month 30 (P ⩽ 0.05, n = 42). There was a concurrent improvement in central macular thickness with a reduction from 502 µm at baseline to 338 µm at year 1 (P ⩽ 0.0001, n = 43). This effect was sustained to year 3 (i.e. 318 µm; P ⩽ 0.0001, n = 29). Mean intraocular pressure (IOP) remained constant between baseline and year 3 with a peak change of 1.9 mm Hg occurring at year 1. Elevated IOP was observed in a similar percentage of patients prior to (22.2% of cases) and following (27.2%) treatment with the FAc implant. In the majority of cases, these elevations were managed effectively with IOP medications.
Conclusions: Despite substantial amounts of prior intravitreal treatments – primarily with anti–vascular endothelial growth factor (VEGF) drugs – this real-world study showed that sustained structural and functional improvements can last for up to 3 years with a single FAc implant.
Der Begriff Neue Medien nimmt in der Regel Bezug auf neue Technologien. In der Medienwissenschaft wird zwischen digitalen und analogen Medien unterschieden. Digitale Medien resultieren aus der Digitalisierung, die in der zweiten Hälfte des 20. Jahrhunderts entwickelt wurde. Digitalisierung bezeichnet den Prozess der Umwandlung von analogen (stetigen) Informationen in eine digitale (schrittweise, numerische) Form. Als digitale Medien werden meist interaktive Medien auf multimedialer und/oder elektronischer Basis bezeichnet, wie zum Beispiel Internet, CD-Roms, DVDs, MP3-Player, Digitalkameras etc. Mit der rasanten Verbreitung digitaler Technologien entwickelte sich erstmals eine komplexe Vernetzung der Geräte untereinander, die weltweit Daten- und Kommunikationsflüsse ermöglicht. Im Spannungsfeld von Technik, Kultur und Gesellschaft stellen digitale Medien weit mehr als technische Systeme dar und bilden einen untrennbaren Bestandteil einer modernen Gesellschaft. Im Laufe der Zeit wurden neue Medien und v. a. ihre tägliche Nutzung einer starken Kritik unterworfen. Wir möchten feststellen, dass wir es im wirklichen Leben sowie auch im täglichen Unterrichtsprozess für viel wichtiger halten, welche Medien, auf welche Art und Weise, zu welchem Zweck und mit welchem Ziel verwendet werden.
Musik ist ein überall präsentes Phänomen und Menschen sind täglich in ständigem Kontakt mit Musik. Beide Phänomene – Musik und Sprache – bauen auf streng festgelegten Grundlagen auf und sind fest im menschlichen Gehirn verankert. In unserer Arbeit präsentieren wir die Ergebnisse der Zusammenarbeit zwischen Linguisten, Neurologen und Musikern, nämlich eine EEG-Studie. Das Hauptziel war es, Unterschiede beim Vergleich der Gehirnreaktionen von Fremdsprachenlernenden und Nicht-Fremdsprachenlernenden auf kommende Reize zu identifizieren. Es wird erwartet, dass diese Identifizierung für den Bereich der Fremdsprachenmethodik fruchtbar sein kann. Unsere Ergebnisse bestätigten die Existenz eines sogenannten dichotomischen Modells des Gehirns (linke Hemisphäre – Sprache, rechte Hemisphäre – Musik).
ISOE-Newsletter 04/2019
(2019)
Alltagsprodukte aus Plastik: Chemikalienmix aus schädlichen und unbekannten Substanzen +++ Kooperationen zwischen Kommunen sichern Lebensqualität im ländlichen Raum +++ IAA im gesellschaftlichen Wandel: Wenn die Verkehrswende der Leitmesse die Show stiehlt +++ „Wasserwende“ gegen Versorgungsengpässe +++ Zielgruppengerechte Ansprache für energieeffizientes und sicheres Wohnen im Alter +++ Wasser in Plastik – Plastik im Wasser. Warum es schwierig ist, die Ökobilanz von PET-Flaschen zu erstellen +++ Lehrveranstaltungen im Wintersemester 2019/20 +++ ISOE unterstützt „Globale Aktionswoche gegen die Klimakrise“ +++ Aus dem ISOE +++ Termine +++ Publikationen
ISOE-Newsletter 05/2019
(2019)
Zukunft gestalten im Anthropozän: Gestaltungsprinzipien für eine kritische Nachhaltigkeitsforschung +++ Institutsbericht 2019 des ISOE erschienen +++ 30 Jahre ISOE: Aufbruch in die Gegenwart. Die sozial-ökologische Zukunft heute gestalten +++ Das ISOE auf Instagram +++ Forschungsergebnisse aus der Schweiz zu nachhaltigem Mobilitätsverhalten +++ Klimaanpassung in den Städten: Was Infrastrukturen dazu beitragen können +++ Kipppunkte in Ökosystemen: Maßnahmen zum Erhalt der Savannen im südlichen Afrika +++ Termine +++ Publikationen
Resistance
(2019)
The term 'resistance', as it appears in the writings of Walter Benjamin, marks the attempt to think a politics that emerges out of a certain experience of history and time. This entry shows that 'Widerstand' is conceived here principally as a resistance against the course of a catastrophic history - a desire for time to cease its flow and come to a standstill.
Im Folgenden erörtert Alexander Nebrig den Zusammenhang zwischen der international anschlussfähigen Philosophie Spinozas in Auerbachs Werk einerseits und der internationalen Verbreitung ebendieses Werkes andererseits. Es geht um die ideellen Eigenschaften von Literatur, die ihren Entstehungs- und primären Vertriebsraum überschreitet und in Übersetzungen Erneuerung findet. Bislang wurden Auerbachs Erzählungen vornehmlich mit dem Pantheismus Spinozas in Verbindung gebracht. Die Spinoza-Rezeption lässt sich aber noch stärker präzisieren. Zu zeigen ist, dass die Affektenlehre der spinozistischen Ethik für Auerbachs Figurenpsychologie strukturbildend wurde (I, II). Im Anschluss an die Überprüfung dieser Hypothese wird in einem zweiten Schritt Auerbachs Spinoza-Rezeption in Verbindung mit seiner Einstellung auf internationale Kontrolle des Werkes gebracht (III, IV). Das neue grenzüberschreitende Verwertungsbewusstsein wurde von der Entstehung des übersetzungsrechtlichen Denkens ermöglicht. Auerbach verfolgte aufmerksam die urheberrechtliche Entwicklung und trat selbst als Lobbyist internationaler Urheberübereinkünfte auf, was ihn zu einem Pionier internationaler Werkherrschaft macht. Leitend ist an dieser Zusammenführung von literarischer Hermeneutik und Urheberrechtsgeschichte die bereits an anderen Fällen erörterte These, dass Vertriebs- und Vermittlungslösungen in einem wechselseitigen Verhältnis mit der Werkstruktur stehen können.
The financial crisis of 2007-08 has stressed the importance of a sound financial system. Unlike other studies weighing the pros and cons of market versus bank-based systems, this paper investigates whether the main elements of the German financial system can be regarded as complementary and consistent. This assessment refers to the idea that there is a potential for positive interaction between different elements in the system that is actually used to make it more valuable to economy and society and more robust to crises. It is shown that the old German bank-based system, where the risk of long-term lending by large private commercial banks was limited by the membership in supervisory boards and strong personal ties between all stakeholders, was a consistent system of well-adjusted complementary elements. After reunification, a hybrid system has emerged where, on the one hand, public savings banks and cooperative banks maintain their role as lenders, but on the other, large private banks have withdrawn from their former dominant role in financing and corporate governance. It is argued that this transition to stronger capital-market and, accordingly, shareholder value orientations has occurred at the expense of consistency.
In his widely acclaimed book “Das Kalte Herz” (The Cold Heart), economic historian Werner Plumpe tells the story of the history of capitalism, which in his view represents a sober form of economics which has proved itself superior and higher performing than other systems. To this day, the long tradition of capitalism criticism has not understood that in capitalism, great wealth is utilized to produce goods that are usually affordable for people with small incomes.
The volume under review is the result of a conference on historical graffiti held at the Ludwig-Maximilians-University of Munich in 2017. The aim of this book is to analyse — for the first time — graffiti from the ancient, medieval and modern periods in their historical and geographical contexts from an interdisciplinary point of view. Following this comparative approach the authors show the tremendous potential of this nascent area of research by investigating epigraphic material that has been neglected and underestimated by scholars for a long time. ...
It is a rare and wonderful thing when a book of 383 pages leaves a reader wanting to read more, much more in fact. That is certainly the case with this intriguing collection of thirteen assorted essays on the Rhine economy from 1815 to the present, organized in six broad topical sections: origins, enterprises, sectors and clusters, infrastructures, transport, and environment. ...
Partant des conditions de mise en place de l’une des dernières commissions d’historiens bilatérales en date – à savoir la commission germano-italienne en 2008 – et du constat de la nature à la fois ambigüe et excessive des attentes formulées à son encontre, cet ouvrage collectif dirigé par deux historiens du temps présent (l’Allemand Christoph Cornelißen et l’Italien Paolo Pezzino) place au cœur de la réflexion la figure de l’historien confronté à une demande d’expertise croissante dans le contexte de l’après guerre froide. Il examine les usages pratiques (voire politiques) des savoirs académiques historiques et leurs effets sur les standards de production de ces savoirs assurant la légitimité professionnelle et sociale des historiens. ...
Within the last decades, western democracies have experienced a rise of inequality, with the gap between lower and upper class citizens steadily increasing and a widespread sentiment of growing inequalities also in the political sphere. Against this background, and in the context of the current “crisis of democracy”, democratic innovations such as direct democratic instruments are discussed as a very popular means to bring citizens back in. However, research on direct democracy has produced rather inconsistent results with regard to the question of which effects referenda and initiatives have on equality. Studies in this field are often limited to single countries and certain aspects of equality. Moreover, most existing studies look at the mere availability of direct democratic instruments instead of actual bills that are put to a vote. This paper aims to take a first step to fill these gaps by giving an explorative overview of the outputs of direct democratic bills on multiple equality dimensions, analyzing all national referenda and initiatives in European democracies between 1990 and 2015. How many pro- and contra-equality bills have been put to a vote, how many of those succeeded at the ballot, and are there differences between country groups? Our findings show that a majority of direct democratic bills was not related to equality at all. Regarding the successful bills, we detect some regional differences along with the general tendency that there are more pro- than contra-equality bills. Our paper sheds new light on the question if direct democracy can serve as an appropriate means to complement representative democracy and to shape democratic institutions in the future. The potential of direct democracy in fostering or impeding equality should be an important criterion for the assessment of claims to extend decision-making by citizens.
This contribution aims to describe privacy, publicness and anonymity as essential analytic dimensions for media linguistic research. The dimensions are not inherent in and predetermined by the technical features and forms of communication provided by mobile devices, but are used by the participants as an orientation grid for shaping their online and offline practices in and with mobile media. Considering both mobile device use in the public realm and the dissemination of increasingly private content in social media (which is said to lead to ‘blurred boundaries’ between the private and the public), the paper provides a brief overview of the main developments in mobile media research: Studies adopting various approaches – e. g. sociological-ethnographic, linguistic and media studies – illustrate how publicness, privacy and anonymity are actively shaped and brought about by mobile media users in face-to-face and remote social encounters. As this shows that publicness, privacy and anonymity are still relevant concepts for users, future media linguistics studies should focus on the dynamic multimodal practices by which they are contextualized and accomplished.
The hillfort settlement of Monkodonja, located in the vicinity of the town Rovinj, is representative of the Bronze Age Castellieri culture in Istria. Twelve years of excavations that lasted one month each year revealed a proto-urban settlement with extensive fortification system, and a tripartite division of its interior that could well reflect the hierarchical social structure of its inhabitants. Remarkably, a change in the fortification concept during the time of the settlement’s existence could also be observed. With regard to bronze objects and ceramic finds the settlement is dated generally between the developed Early Bronze Age and the beginning of the Middle Bronze Age, or in Br A2 and Br B1 periods according to the chronology of Paul Reinecke. Moreover, about 40 radiocarbon dates from the Monkodonja settlement have also been analysed. The foundation of the settlement is dated to around 1800 cal BC. The second extensive building phase, including the rebuilding of the fortification system according to new defensive concepts, is dated approximately to 1600 cal BC, while the destruction of the settlement occurred around 1500 cal BC or in the middle of the 15th century BC at the latest.
Hofmannsthal ist seit seiner Kindheit mit der orientalischen Welt vertraut. Erst nach langjähriger Beschäftigung mit dem Orient hat Hofmannsthal eine Reise in den Orient unternommen. Hofmannsthals "Reise nach Nordafrika" im Jahre 1925 war sein erster und letzter direkter Kontakt mit dem Orient. Er reiste mit der Familie Zifferer nach Marokko, Algerien und Tunesien. Die Städte Fés und Saleh hatten ihn beeindruckt. Er schrieb einen Reisebericht über diese Reise. Der erste Teil seines Reiseberichts Fez berichtet über die Atmosphäre der Stadt und die Einwohner sowie Hofmannsthals Eindrücke und Wahrnehmungen. Er wurde am 12. April 1925 im Berliner Tageblatt publiziert. Im zweiten Teil des Berichts "Das Gespräch in Saleh" handelt es sich um ein Gespräch über das Vorhandensein der Franzosen in Marokko und Reflexionen über die französische und die deutsche Sprache und Kultur. Er wurde am 31. Mai 1925 in der Wiener Freien Presse veröffentlicht. In diesem Aufsatz wird Hofmannsthals Orientbild anhand seines Reiseberichts analysiert.
Immunosuppressive compounds affect the fungal growth and viability of defined aspergillus species
(2019)
Immunosuppressive drugs are administered to a number of patients; e.g., to allogeneic hematopoietic stem cell transplant recipients. Immunosuppressive drugs impair the immune system and thus increase the risk of invasive fungal disease, but may exhibit antifungal activity at the same time. We investigated the impact of various concentrations of three commonly used immunosuppressive compounds—cyclosporin A (CsA), methylprednisolone (mPRED), and mycophenolic acid (MPA)—on the growth and viability of five clinically important Aspergillus species. Methods included disc diffusion, optical density of mycelium, and viability assays such as XTT. MPA and CsA had a species-specific and dose-dependent inhibitory effect on the growth of all Aspergillus spp. tested, although growth inhibition by MPA was highest in A. niger, A. flavus and A. brasiliensis. Both agents exhibited species-specific hyphal damage, which was higher when the immunosuppressants were added to growing conidia than to mycelium. In contrast, mPRED increased the growth of A. niger, but had no major impact on the growth and viability of any of the other Aspergillus species tested. Our findings may help to better understand the interaction of drugs with Aspergillus species and ultimately may have an impact on individualizing immunosuppressive therapy.
Suppression of light nuclei production in collisions of small systems at the Large Hadron Collider
(2019)
We show that the recently observed suppression of the yield ratio of deuteron to proton and of helium-3 to proton in p+p collisions compared to those in p+Pb or Pb+Pb collisions by the ALICE Collaboration at the Large Hadron Collider (LHC) can be explained if light nuclei are produced from the coalescence of nucleons at the kinetic freeze-out of these collisions. This suppression is attributed to the non-negligible sizes of deuteron and helium-3 compared to the size of the nucleon emission source in collisions of small systems, which reduces the overlap of their internal wave functions with those of nucleons. The same model is also used to study the production of triton and hypertriton in heavy-ion collisions at the LHC. Compared to helium-3 in events of low charged particle multiplicity, the triton is less suppressed due to its smaller size and the hypertriton is even more suppressed as a result of its much larger size.
The term structure of interest rates is crucial for the transmission of monetary policy to financial markets and the macroeconomy. Disentangling the impact of monetary policy on the components of interest rates, expected short rates and term premia, is essential to understanding this channel. To accomplish this, we provide a quantitative structural model with endogenous, time-varying term premia that are consistent with empirical findings. News about future policy, in contrast to unexpected policy shocks, has quantitatively significant effects on term premia along the entire term structure. This provides a plausible explanation for partly contradictory estimates in the empirical literature.
We study how the mass and magnetic moment of the quarks are dynamically generated in nonequilibrium quark matter. We derive the equal-time transport and constraint equations for the quark Wigner function in a magnetized quark model and solve them in the semi-classical expansion. The quark mass and magnetic moment are self-consistently coupled to the Wigner function and controlled by the kinetic equations. While the quark mass is dynamically generated at the classical level, the quark magnetic moment is a pure quantum effect, induced by the quark spin interaction with the external magnetic field.
In the course of the crisis, the European System of Central Banks (ESCB) has acted several times to support the EU Member States and banking systems in financial distress by purchasing debt instruments: Covered Bonds Programmes (CBP), Securities Market Programmes (SMP), Long Term Refinancing Operations (LTRO), and Targeted Long Term Refinancing Operations (TLTRO), followed by the Outright Monetary Transactions (OMT) and then the Extended Asset Purchase Programmes (EAPP) – colloquially labelled as Quantitative Easing (QE).
Initially, the support measures of the ESCB might have to be judged as monetary policy but the selectivity of OMT and – even more – SMP in conjunction with the transfer of risks to the ESCB speak against it.
Ceritinib-induced regression of an insulin-like growth factor-driven neuroepithelial brain tumor
(2019)
The insulin-like growth factor (IGF) pathway plays an important role in several brain tumor entities. However, the lack of inhibitors crossing the blood–brain barrier remains a significant obstacle for clinical translation. Here, we targeted the IGF pathway using ceritinib, an off-target inhibitor of the IGF1 receptor (IGF1R) and insulin receptor (INSR), in a pediatric patient with an unclassified brain tumor and a notch receptor 1 (NOTCH1) germline mutation. Pathway analysis of the tumor revealed activation of the sonic hedgehog (SHH), the wingless and integrated-1 (WNT), the IGF, and the Notch pathway. The proliferation of the patient tumor cells (225ZL) was inhibited by arsenic trioxide (ATO), which is an inhibitor of the SHH pathway, by linsitinib, which is an inhibitor of IGF1R and INSR, and by ceritinib. 225ZL expressed INSR but not IGF1R at the protein level, and ceritinib blocked the phosphorylation of INSR. Our first personalized treatment included ATO, but because of side effects, we switched to ceritinib. After 46 days, we achieved a concentration of 1.70 µM of ceritinib in the plasma, and after 58 days, MRI confirmed that there was a response to the treatment. Ceritinib accumulated in the tumor at a concentration of 2.72 µM. Our data suggest ceritinib as a promising drug for the treatment of IGF-driven brain tumors.
Der betongraue Bunker ist von Zwangsarbeitern der Nationalsozialisten im Zweiten Weltkrieg errichtet worden. Geplant war er als Luftschutzbunker für die Mitarbeiter und Kunden der Reichsbahn, damit sie sich im Ernstfall vom nah gelegenen Bahnhof, dem heutigen Bahnhof Friedrichstrasse, vor dem Bombenhagel retten konnten; bis zu 2.500 Menschen finden darin Platz. Nach dem Ende des Zweiten Weltkrieges wurde der Bunker sehr unterschiedlich genutzt: Zuerst diente er als Kriegsgefängnis der Roten Armee, danach als Lager für Textilien und anschließend für Südfrüchte, was ihm den Namen „Bananenbunker“ einbrachte. Nach dem Mauerfall ging das Gebäude in den Besitz des Bundes über und die Kultur Berlins zog ein: Erst in Form eines Techno-Clubs, in welchem auch Theaterstücke aufgeführt wurden, bis der Bund das Gebäude vorerst schloss. Der Werbeagentur-Inhaber Christian Boros erwarb zusammen mit seiner Frau Karen Boros den Bunker schließlich und baute ihn fünf Jahre lang um: Seit 2008 werden die Kunstwerke aus Boros’ privater Kunstsammlung präsentiert. ...
The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet, the molecular determinants governing interactions in protein-RNA networks are not well understood. Here we investigated the relationship between the structure of an RNA and its ability to interact with proteins. Analysing in silico, in vitro and in vivo experiments, we find that the amount of double-stranded regions in an RNA correlates with the number of protein contacts. This relationship —which we call structure-driven protein interactivity— allows classification of RNA types, plays a role in gene regulation and could have implications for the formation of phase-separated ribonucleoprotein assemblies. We validate our hypothesis by showing that a highly structured RNA can rearrange the composition of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs.
Rhabdomyosarcomas are the most common pediatric soft tissue sarcoma and are a major cause of death from cancer in young patients requiring new treatment options to improve outcomes. High-risk patients include those with metastatic or relapsed disease and tumors with PAX3-FOXO1 fusion genes that encode a potent transcription factor that drives tumourigenesis through transcriptional reprogramming. Polo-Like Kinase-1 (PLK1) is a serine/threonine kinase that phosphorylates a wide range of target substrates and alters their activity. PLK1 functions as a pleiotropic master regulator of mitosis and regulates DNA replication after stress. Taken together with high levels of expression that correlate with poor outcomes in many cancers, including rhabdomyosarcomas, it is an attractive therapeutic target. This is supported in rhabdomyosarcoma models by characterization of molecular and phenotypic effects of reducing and inhibiting PLK1, including changes to the PAX3-FOXO1 fusion protein. However, as tumor re-growth has been observed, combination strategies are required. Here we review preclinical evidence and consider biological rationale for PLK1 inhibition in combination with drugs that promote apoptosis, interfere with activity of PAX3-FOXO1 and are synergistic with microtubule-destabilizing drugs such as vincristine. The preclinical effects of low doses of the PLK1 inhibitor volasertib in combination with vincristine, which is widely used in rhabdomyosarcoma treatment, show particular promise in light of recent clinical data in the pediatric setting that support achievable volasertib doses predicted to be effective. Further development of novel therapeutic strategies including PLK1 inhibition may ultimately benefit young patients with rhabdomyosarcoma and other cancers.
Since Inhibitor of Apoptosis (IAP) proteins have been implicated in cellular adaptation to endoplasmic reticulum (ER) stress, we investigated the regulation of ER stress-induced apoptosis by small-molecule second mitochondria-derived activator of caspase (Smac) mimetics that antagonize IAP proteins. Here, we discover that Smac mimetic suppresses tunicamycin (TM)-induced apoptosis via resolution of the unfolded protein response (UPR) and ER stress. Smac mimetics such as BV6 selectively inhibit apoptosis triggered by pharmacological or genetic inhibition of protein N-glycosylation using TM or knockdown of DPAGT1, the enzyme that catalyzes the first step of protein N-glycosylation. In contrast, BV6 does not rescue cell death induced by other typical ER stressors (i.e., thapsigargin (TG), dithiothreitol, brefeldin A, bortezomib, or 2-deoxyglucose). The protection from TM-triggered apoptosis is found for structurally different Smac mimetics and for genetic knockdown of cellular IAP (cIAP) proteins in several cancer types, underlining the broader relevance. Interestingly, lectin microarray profiling reveals that BV6 counteracts TM-imposed inhibition of protein glycosylation. BV6 consistently abolishes TM-stimulated accumulation of ER stress markers such as glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and reduces protein kinase RNA-like ER kinase (PERK) phosphorylation and X box-binding protein 1 (XBP1) splicing upon TM treatment. BV6-stimulated activation of nuclear factor-κB (NF-κB) contributes to the resolution of ER stress, since NF-κB inhibition by overexpression of dominant-negative IκBα superrepressor counteracts the suppression of TM-stimulated transcriptional activation of CHOP and GRP78 by BV6. Thus, our study is the first to show that Smac mimetic protects from TM-triggered apoptosis by resolving the UPR and ER stress. This provides new insights into the regulation of cellular stress responses by Smac mimetics.
Telecommunications Law and Practice in Nigeria -Perspectives on Consumer Protection is intended primarily to provide an indigenous source of information on the theoretical and legal framework of the regulation of telecommunications in Nigeria with respect to how such legal framework assists in addressing the consumers problems in the field of telecommunications. The book covers the evolution of telecommunications the world over and its variant in Nigeria, a variety of issues including the early controlling organs, regulatory regimes, the deregulation era, interconnectivity and privacy law, telecommunications and intellectual property, international trade and drafting of international trade contracts, encryption technology and privacy in telecommunications. The book should be an invaluable companion on the Nigerian telecommunications law and practice with perspectives on consumer protection.
Highlighting the problematiques of working with a narrow version of greenhouse effects or global warming, this book posits the theory of necroclimatism that encompasses broader versions of greenhouse effects and global warming. Conceiving cultures, societies, moral sensibilities, epistemologies, polities, economies, legal systems and religions of the formerly colonised peoples as greenhoused and entrapped in the heat of global apartheid and neo-colonialism, the book refuses to be confined to the pufferies of physical conceptualisations of greenhousing and global warming. Underlining the supposed disposability and dispensability of colonised peoples, the notion of necroclimatism explicates ways in which some people suffer various forms of death, which have increasingly become a feature of global apartheid and neo-colonialism that are cast in spectral sacrificial logics. Deemed to constitute disposable bodies, disposable cultures, disposable polities, disposable societies, disposable epistemologies, disposable religions, disposable laws and disposable economies, the sacrificed are, in the age of climate catastrophism, once again reminded that they have duties to die, to become extinct in order to save the global spaceship that is sinking due to climate change and global warming. This book therefore argues that in a sacrificial world (dis)order, binaries between humans and animals, good and evil, moral and immoral, the dead and the living necessarily vanish in the nefarious logic of what marks the era of climate catastrophism and the attendant necroclimatism. The book further argues that a sacrificial world (dis)order is necessarily a posthumanist and postanthropocentric world (dis)order, which should be never granted space in African worlds and even beyond. The book thus, raises fundamental questions for African anticipatory regimes, and for this reason it is handy for scholars in political science, sociology, social anthropology, development studies, environmental studies, agricultural studies, legal studies, food science, geography, religious studies and decolonial fields of studies.