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The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and-extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. (C) 2017 AACR.
Проведен анализ пространственной семантики различных категорий русских существительных, входящих в психолингви-стическую базуданных; особое внимание уделяется абстрактным концептам. Выявлены различия пространственной семантики наименований физических ощущений и действий, эмоций, ментальных процессов. Полученны ерезультаты обсуждаются с точки зрения отдельных подходов в рамках теории воплощенного познания – теории концептуальной метафоры, теории слов как социальных инструментов (WAT, Words As social Tools), нейросемантики.
The conversion of light energy into other molecular energetic degrees of freedom is often dominated by ultrafast, non-adiabatic processes. Femtosecond spectroscopy with optical pulses has helped in shaping our understanding of crucial processes in molecular energy-conversion. The advent of new, ultrashort and bright X-ray free electron laser sources opens the possibility to use X-ray-typical element and site sensitivity for ultrafast molecular research. We present two types of spectroscopy, ultrafast Auger and ultrafast X-ray absorption spectroscopy, and discuss their sensitivity to molecular processes. While Auger spectroscopy is able to monitor bond distance changes in the vicinity of an X-ray created core hole, near-edge absorption spectroscopy can deliver high-fidelity information on non-adiabatic transitions involving lone-pair orbitals. We demonstrate these features on the example of the UV-excited nucleobase thymine, investigated at the oxygen K-edge. We find a C-O bond elongation in the Auger data in addition to pi pi*/n pi* non-adiabatic transition in X-ray near-edge absorption. We compare the results from both methods and draw a conclusive scenario of non-adiabatic molecular relaxation after UV excitation.
The Upper Cretaceous (Campanian-Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is compared to newly discovered contourite drifts in the Maldives. Like the drift deposits in the Maldives, the Orfento Formation fills a channel and builds a Miocene delta-shaped and mounded sedimentary body in the basin that is similar in size to the approximately 350 km(2) large coarse-grained bioclastic Miocene delta drifts in the Maldives. The composition of the bioclastic wedge of the Orfento Formation is also exclusively bioclastic debris sourced from the shallow-water areas and reworked clasts of the Orfento Formation itself. In the near mud-free succession, age-diagnostic fossils are sparse. The depositional textures vary from wackestone to float-rudstone and breccia/conglomerates, but rocks with grainstone and rudstone textures are the most common facies. In the channel, lensoid convex-upward breccias, cross-cutting channelized beds and thick grainstone lobes with abundant scours indicate alternating erosion and deposition from a high-energy current. In the basin, the mounded sedimentary body contains lobes with a divergent progradational geometry. The lobes are built by decametre thick composite megabeds consisting of sigmoidal clinoforms that typically have a channelized topset, a grainy foreset and a fine-grained bottomset with abundant irregular angular clasts. Up to 30 m thick channels filled with intraformational breccias and coarse grainstones pinch out downslope between the megabeds. In the distal portion of the wedge, stacked grainstone beds with foresets and reworked intraclasts document continuous sediment reworking and migration. The bioclastic wedge of the Orfento Formation has been variously interpreted as a succession of sea-level controlled slope deposits, a shoaling shoreface complex, or a carbonate tidal delta. Current-controlled delta drifts in the Maldives, however, offer a new interpretation because of their similarity in architecture and composition. These similarities include: (i) a feeder channel opening into the basin; (ii) an excavation moat at the exit of the channel; (iii) an overall mounded geometry with an apex that is in shallower water depth than the source channel; (iv) progradation of stacked lobes; (v) channels that pinch out in a basinward direction; and (vi) smaller channelized intervals that are arranged in a radial pattern. As a result, the Upper Cretaceous (Campanian-Maastrichtian) bioclastic wedge of the Orfento Formation in the Montagna della Maiella, Italy, is here interpreted as a carbonate delta drift.
Language and aging research
(2019)
Our introduction to the special collection gives an overview of the research projects which were originally presented at the third CLARe network conference. We group the research under four cross-sectional topics that unite the different contributions: the data used in the research, the theoretical frameworks, the languages and varieties which are represented and the situational contexts which are examined. These projects represent the current state of research in this field and allows the reader to orient themselves within this diverse field but also leaves many questions open and provides impetus for future lines of research. The interaction and collaboration between diverse disciplines is the central aspect which unites all contributions to the special collection.
Das Rahmenkonzept der Universitätsschule Potsdam beschreibt die Wertegrundlage und das pädagogisch-didaktische sowie das wissenschaftliche Fundament einer zu gründenden Universitätsschule Potsdam. Wie andere Universitätsschulen soll sich auch diese Schule durch eine enge und institutionalisierte Beziehung zwischen Schule und Universität auszeichnen, die den ständigen Wissenstransfer zwischen Schulpraxis, Wissenschaft, Lehrkräftebildung und Schulverwaltung unterstützt. Das Rahmenkonzept legt die Grundlagen für eine inklusive Schule, deren Schüler:innen einen Querschnitt der Gesellschaft abbilden, und die in ungleichheitssensiblen Bildungsangeboten alle Bildungsabschlüsse des Landes Brandenburg anbietet. Die Universitätsschule soll den starken Segregationsprozessen in Potsdam entgegenwirken.
Im Leitbild werden die Grundwerte (Nachhaltigkeit, Inklusion und Bildungsgerechtigkeit, Menschenrechte und Demokratie, Gemeinschaft, Ganzheitlichkeit) und die Bildungsziele (Transferfähigkeit, kritisch-reflexives Denken und lebensbegleitendes Lernen, Diversitätsbewusstsein und Transkulturalität, Selbstkompetenz und Beziehungskompetenz, Kulturtechniken und digitale Kompetenz) der Universitätsschule dargestellt. Das Pädagogische Konzept veranschaulicht, wie Werte und Bildungsziele in den Bereichen Schulform, Schulkultur, Lernkultur sowie Lernorte und Lernumgebung ausgestaltet werden können. Schließlich wird die Universitätsschule als lernende und lehrende Institution beschrieben, die ein Ort des Transfers von Bildungsinnovationen ist. Dafür soll eine Transferwerkstatt in der Schule verankert werden, die den Wissensaustausch der schulrelevanten Akteur:innen unterstützt und gestaltet.
Die ersten 40 Rechtsprofessoren der Viadrina immatrikulierten sich von 1506 bis 1571 in Frankfurt an der Oder. Sie lassen sich in zwei Gruppen einteilen, die von der Gründung der Universität 1506 bis 1539 Immatrikulierten und die nach Einführung der Reformation im Kurfürstentum Brandenburg 1539/40 bis zum Regierungsantritt des Kurfürsten Johann Georg von Brandenburg 1571 an der Viadrina eingeschriebenen Juristen. Die Profile der vorreformatorischen und der nachreformatorischen Rechtsexperten weisen Gemeinsamkeiten, z.B. die Eheschließung, aber auch Unterschiede auf. Am besten illustriert das Beispiel der Rechtsprofessorendynastien Zoch und Köppen die "Familienuniversität" Viadrina.
Mildred Harnack, geb. Fish, stammte ursprünglich aus Milwaukee, Wisconsin. Zusammen mit ihrem Ehemann Arvid Harnack zog sie nach Deutschland und lebte seit 1930 in Berlin. Hier lehrte die Literaturwissenschaftlerin an der Friedrich-Wilhelms-Universität (heute Humboldt-Universität) und am Berliner Abendgymnasium (heute Peter A. Silbermann-Schule). Bereits kurz nach der Machtübernahme von Adolf Hitler hatte sich um das Ehepaar Harnack ein Kreis von Freunden gebildet, der gegen die Herrschaft der Nationalsozialisten opponierte. Dazu zählten auch Karl Behrens und Bodo Schlösinger, die beide Schüler Mildred Harnacks am Berliner Abendgymnasium waren. Mildred Harnack konnte mit Hilfe ihrer Kontakte zur amerikanischen Botschaft ihren Schülern im nationalsozialistischen Deutschland ansonsten nicht zugängliche Informationen besorgen.
Aufgrund von Funkkontakten des Freundeskreises zur Sowjetunion wurde die Gruppe von den Nationalsozialisten Rote Kapelle genannt – „rot“ bezog sich auf deren linke Haltung und mit „Kapelle“ wurden Funker assoziiert, die wie Pianisten in einer Kapelle spielen. Der Berliner Oppositionszirkel umfasste bis zu seiner Zerschlagung durch die Nationalsozialisten etwa 150 Personen verschiedenster Berufsgruppen, unterschiedlicher parteipolitischer Einstellungen und Konfessionen. Die Gruppe verfertigte oppositionelle Flugblätter und lieferte Informationen an die amerikanische Botschaft sowie an die Sowjetunion. Mildred Harnack wurde – wie viele ihrer Mitstreiterinnen und Mitstreiter – nach ihrer Verhaftung vom Reichskriegsgericht zum Tode verurteilt und am 16. Februar 1943 in Plötzensee guillotiniert.
In diesem Band stellen Studierende der Universität Potsdam sowie Hörerinnen und Hörer der Peter A. Silbermann-Schule (Berlin) nach einem kurzen Überblick zum Widerstand gegen den Nationalsozialismus in Deutschland das Netzwerk der Roten Kapelle sowie die Biographien von Mildred Harnack und ihren Schülern Karl Behrens und Bodo Schlösinger vom Berliner Abendgymnasium eindrücklich vor.
Zinc protoporphyrin IX (ZnPP) is known to accumulate in most meat products during storage. However, the pathway of its formation is not yet completely clarified. To gain more insights into the specificity of ZnPP occurrence, a SEC-HPLC-UV-fluorescence setup was established to screen the proteins in aqueous meat extracts for their ZnPP fluorescence during incubation. In accordance with previous studies it was identified by SDS-PAGE and MALDI-TOF-MS that ZnPP formation takes place in myoglobin. In this study, valuable new insights into the ZnPP forming pathway were gained, as our results indicated that a significant part of ZnPP - after being formed within the protein - is transitioned into free ZnPP during incubation. Additionally, the obtained results implied that ZnPP may also occur in proteins of higher molecular weight (> 100 kDa).
A nova is a cataclysmic event on the surface of a white dwarf in a binary system that increases the overall brightness by several orders of magnitude. Although binary systems with a white dwarf are expected to be overabundant in globular clusters compared with in the Galaxy, only two novae from Galactic globular clusters have been observed. We present the discovery of an emission nebula in the Galactic globular cluster M 22 (NGC 6656) in observations made with the integral-field spectrograph MUSE. We extracted the spectrum of the nebula and used the radial velocity determined from the emission lines to confirm that the nebula is part of NGC 6656. Emission-line ratios were used to determine the electron temperature and density. It is estimated to have a mass of 1-17 x 10(-5) M-circle dot. This mass and the emission-line ratios indicate that the nebula is a nova remnant. Its position coincides with the reported location of a "guest star", an ancient Chinese term for transients, observed in May 48 BCE. With this discovery, this nova may be one of the oldest confirmed extra-solar events recorded in human history.
Almost half of the political life has been experienced under the state of emergency and state of siege policies in the Turkish Republic. In spite of such a striking number and continuity in the deployment of legal emergency powers, there are just a few legal and political studies examining the reasons for such permanency in governing practices. To fill this gap, this paper aims to discuss one of the most important sources of the ‘permanent’ political crisis in the country: the historical evolution of legal emergency power. In order to highlight how these policies have intensified the highly fragile citizenship regime by weakening the separation of power, repressing the use of political rights and increasing the discretionary power of both the executive and judiciary authorities, the paper sheds light on the emergence and production of a specific form of legality based on the idea of emergency and the principle of executive prerogative. In that context, it aims to provide a genealogical explanation of the evolution of the exceptional form of the nation-state, which is based on the way political society, representation, and legitimacy have been instituted and accompanying failure of the ruling classes in building hegemony in the country.
In nature, plants interact with numerous beneficial or pathogenic soil-borne microorganisms. Plants have developed various defense strategies to expel pathogenic microbes, some of which function soon after pathogen infection. We used Medicago truncatula and its oomycete pathogen Aphanomyces euteiches to elucidate early responses of the infected root. A. euteiches causes root rot disease in legumes and is a limiting factor in legume production. Transcript profiling of seedlings and adult plant roots inoculated with A. euteiches zoospores for 2 h revealed specific upregulation of a gene encoding a putative sesquiterpene synthase (M. truncatula TERPENE SYNTHASE 10 [MtTPS10]) in both developmental stages. MtTPS10 was specifically expressed in roots upon oomycete infection. Heterologous expression of MtTPS10 in yeast led to production of a blend of sesquiterpenes and sesquiterpene alcohols, with NMR identifying a major peak corresponding to himalachol. Moreover, plants carrying a tobacco (Nicotiana tabacum) retrotransposon Tnt1 insertion in MtTPS10 lacked the emission of sesquiterpenes upon A. euteiches infection, supporting the assumption that the identified gene encodes a multiproduct sesquiterpene synthase. Mttps10 plants and plants with reduced MtTPS10 transcript levels created by expression of an MtTPS10-artificial microRNA in roots were more susceptible to A. euteiches infection than were the corresponding wild-type plants and roots transformed with the empty vector, respectively. Sesquiterpenes produced by expression of MtTPS10 in yeast also inhibited mycelial growth and A. euteiches zoospore germination. These data suggest that sesquiterpene production in roots by MtTPS10 plays a previously unrecognized role in the defense response of M. truncatula against A. euteiches.
This study addresses the question of how age of acquisition (AoA) affects grammatical processing, specifically with respect to inflectional morphology, in bilinguals. We examined experimental data of more than 100 participants from the Russian/German community in Berlin, all of whom acquired Russian from birth and German at different ages. Using the cross-modal lexical priming technique, we investigated stem allomorphs of German verbs that encode multiple morphosyntactic features. The results revealed a striking AoA modulation of observed priming patterns, indicating efficient access to morphosyntactic features for early AoAs and a gradual decline with increasing AoAs. In addition, we found a discontinuity in the function relating AoA to morphosyntactic feature access, suggesting a sensitive period for the development of morphosyntax.
It is a common finding across languages that young children have problems in understanding patient-initial sentences. We used Tagalog, a verb-initial language with a reliable voice-marking system and highly frequent patient voice constructions, to test the predictions of several accounts that have been proposed to explain this difficulty: the frequency account, the Competition Model, and the incremental processing account. Study 1 presents an analysis of Tagalog child-directed speech, which showed that the dominant argument order is agent-before-patient and that morphosyntactic markers are highly valid cues to thematic role assignment. In Study 2, we used a combined self-paced listening and picture verification task to test how Tagalog-speaking adults and 5- and 7-year-old children process reversible transitive sentences. Results showed that adults performed well in all conditions, while children’s accuracy and listening times for the first noun phrase indicated more difficulty in interpreting patient-initial sentences in the agent voice compared to the patient voice. The patient voice advantage is partly explained by both the frequency account and incremental processing account.
Context. Massive Wolf-Rayet (WR) stars dominate the radiative and mechanical energy budget of galaxies and probe a critical phase in the evolution of massive stars prior to core collapse. It is not known whether core He-burning WR stars (classical WR; cWR) form predominantly through wind stripping (w-WR) or binary stripping (b-WR). Whereas spectroscopy of WR binaries has so-far largely been avoided because of its complexity, our study focuses on the 44 WR binaries and binary candidates of the Large Magellanic Cloud (LMC; metallicity Z approximate to 0.5 Z(circle dot)), which were identified on the basis of radial velocity variations, composite spectra, or high X-ray luminosities. Aims. Relying on a diverse spectroscopic database, we aim to derive the physical and orbital parameters of our targets, confronting evolution models of evolved massive stars at subsolar metallicity and constraining the impact of binary interaction in forming these stars. Methods. Spectroscopy was performed using the Potsdam Wolf-Rayet (PoWR) code and cross-correlation techniques. Disentanglement was performed using the code Spectangular or the shift-and-add algorithm. Evolutionary status was interpreted using the Binary Population and Spectral Synthesis (BPASS) code, exploring binary interaction and chemically homogeneous evolution. Results. Among our sample, 28/44 objects show composite spectra and are analyzed as such. An additional five targets show periodically moving WR primaries but no detected companions (SB1); two (BAT99 99 and 112) are potential WR + compact-object candidates owing to their high X-ray luminosities. We cannot confirm the binary nature of the remaining 11 candidates. About two-thirds of the WN components in binaries are identified as cWR, and one-third as hydrogen-burning WR stars. We establish metallicity-dependent mass-loss recipes, which broadly agree with those recently derived for single WN stars, and in which so-called WN3/O3 stars are clear outliers. We estimate that 45 +/- 30% of the cWR stars in our sample have interacted with a companion via mass transfer. However, only approximate to 12 +/- 7% of the cWR stars in our sample naively appear to have formed purely owing to stripping via a companion (12% b-WR). Assuming that apparently single WR stars truly formed as single stars, this comprises approximate to 4% of the whole LMC WN population, which is about ten times less than expected. No obvious differences in the properties of single and binary WN stars, whose luminosities extend down to log L approximate to 5.2 [L-circle dot], are apparent. With the exception of a few systems (BAT99 19, 49, and 103), the equatorial rotational velocities of the OB-type companions are moderate (v(eq) less than or similar to 250 km s(-1)) and challenge standard formalisms of angular-momentum accretion. For most objects, chemically homogeneous evolution can be rejected for the secondary, but not for the WR progenitor. Conclusions. No obvious dichotomy in the locations of apparently single and binary WN stars on the Hertzsprung-Russell diagram is apparent. According to commonly used stellar evolution models (BPASS, Geneva), most apparently single WN stars could not have formed as single stars, implying that they were stripped by an undetected companion. Otherwise, it must follow that pre-WR mass-loss/mixing (e.g., during the red supergiant phase) are strongly underestimated in standard stellar evolution models.
The German Sonderweg thesis has been discarded in most research fields. Yet in regards to the military, things differ: all conflicts before the Second World War are interpreted as prelude to the war of extermination between 1939-1945. This article specifically looks at the Franco-Prussian War 1870-71 and German behaviour vis-a-vis regular combatants, civilians and irregular guerrilla fighters, the so-called francs-tireurs. The author argues that the counter-measures were not exceptional for nineteenth century warfare and also shows how selective reading of the existing secondary literature has distorted our view on the war.
Der vorliegende Artikel analysiert aus organisationssoziologischer Perspektive, warum die polizeilichen NSU-Ermittlungen auch nach jahrelang erfolglosen Untersuchungen im Bereich der Organisierten Kriminalität eine rechtsextremistische Urheberschaft der NSU-Morde ausschlossen. Um diese Frage zu beantworten, bedient sich der Artikel einer entscheidungstheoretischen Routine- und Lernperspektive. Das mit diesem theoretischen Instrumentarium verfolgte Ziel liegt in der Analyse der Lernobstruktionen der polizeilichen Ermittlungen im NSU-Komplex. Darauf aufbauend werden empirische und analytische Anschlussperspektiven aufgezeigt.