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The Tijanya brotherhood founded by Cheikh Ahmed TIJANI in the second half of the XVIIIth century achieved a spectacular breakthrough in West Africa by the middle of the XIXth century. It was adopted and championed by the main figures of the resistance to the French colonial penetration : Cheikh Umar al-Futi TALL and Ahmadou Mahdiyu BA who were introduced to it respectively by Mohamed el-Ghali in Medina and Mohamed el-Hafez, and Id-on-Ali in Mederdra, Mauritania. Mamadou Lamine Dramé from the Gajaaga and Samba Diadana Ac also were figures of the anticolonial resistance who embraced Tijanya. Ahmadou Cheikhou, Cheikh Umar TALL's successor and eldest son, too was a tijane anticolonial hero whom Archinard's men killed in 1891, after his empire had gone through a long period of turmoil.
Motivated by recent experimental suggestions of charge-order-driven ferroelectricity in organic charge-transfer salts, such as κ-(BEDT-TTF)2Cu[N(CN)2]Cl, we investigate magnetic and charge-ordered phases that emerge in an extended two-orbital Hubbard model on the anisotropic triangular lattice at 3/4 filling. This model takes into account the presence of two organic BEDT-TTF molecules, which form a dimer on each site of the lattice, and includes short-range intramolecular and intermolecular interactions and hoppings. By using variational wave functions and quantum Monte Carlo techniques, we find two polar states with charge disproportionation inside the dimer, hinting to ferroelectricity. These charge-ordered insulating phases are stabilized in the strongly correlated limit and their actual charge pattern is determined by the relative strength of intradimer to interdimer couplings. Our results suggest that ferroelectricity is not driven by magnetism, since these polar phases can be stabilized also without antiferromagnetic order and provide a possible microscopic explanation of the experimental observations. In addition, a conventional dimer-Mott state (with uniform density and antiferromagnetic order) and a nonpolar charge-ordered state (with charge-rich and charge-poor dimers forming a checkerboard pattern) can be stabilized in the strong-coupling regime. Finally, when electron–electron interactions are weak, metallic states appear, with either uniform charge distribution or a peculiar 12-site periodicity that generates honeycomb-like charge order.
Au Tchad, à cause de ses retombées financières une attention particulière est prêtée aux arbres à karité (Vitella- ria paradoxa C.F.Gaertn.). Cependant, cette culture est menacée par les plantes vasculaires parasites de la famille des Lo- ranthaceae. La présente étude a été effectuée dans 3 sites dans la région du Mandoul pour évaluer l’ampleur des attaques de Loranthaceae (gui africain) sur des arbres en fonction des classes de circonférence du tronc à 1,5 cm du sol. Elle a consisté à dénombrer sur une de surface, les arbres à karité infestés et les touffes de parasites rencontrées sur ces arbres, afin de dé- terminer leur taux et leur intensité d’infestation. Les résultats obtenus montrent que Tapinanthus dodoneifolus (DC) Danser a été trouvée comme la seule espèce de Loranthaceae qui parasite les arbres karité étudiés dans la zone d’étude. Le taux moyen d’infestation estimé à 73% augmente avec l’âge des arbres karité. La moyenne d’intensité de l’infestation/arbre (2,75 touffes à Békôh, 2,27 à Yomi and 2,04 à Bébopen) montre que Tapinanthus dodoneifolus constitue une réelle menace pour les peu- plements de karité dans la zone d’étude. Il reste à rechercher le seuil d’infestation qui provoque une réduction significative de la fructification. Pour l’instant, bien que pénible à cause de la hauteur des arbres adultes, la lutte mécanique contre les Ta- pinanthus par la coupe systématique des branches infestées est urgente dans les parcs à karité dans cette zone d’étude.
A 24-year-old patient from Cameroon presented to our hospital because of a foreign structure in her left eye. To our knowledge, for the first time, fluorescent microscopy revealed motile microfilariae, and the diagnosis of loiasis was established. Despite substantial microfilaremia, eosinophilia only unmasked after the initiation of antiparasitic therapy.
Background: In the past, protease inhibitors (PIs) and the reverse transcriptase inhibitor abacavir were identified increasing the risk for thromboembolic complications and cardiovascular events (CVE) of HIV infected patients taking a combination antiretroviral therapy (cART). Results of the previous HIV-PLA I-study lead to the assumption that platelet activation could play a substantial role in increasing CVE risks.
Methods: The open label, monocentric HIV-PLA II-study investigated HIV-1-infected, therapy-naïve adults (n=45) starting with cART, consisting either of boosted PI (atazanavir, n= 6, darunavir, n=11), NNRTI (efavirenz, n=14) or integrase inhibitor (raltegravir, n=14), each plus tenofovir/emtricitabine co-medication. Main exclusion criteria were tobacco smoking, the intake of NSAIDs or abacavir or past CVE. Platelet adhesive molecule p-selectin (CD62P) and FITC anti-human Integrin α-IIb/Integrin β-3 (CD41/CD61) antibody (PAC-1) binding, monocyte CD11b/monocyte-associated CD41 expression and the endogenous thrombin potential (ETP) were assessed ex vivo-in vitro at baseline, weeks 4, 12 and 24. Therapy regimens were blinded to the investigators for laboratory and statistical analyses.
Results: CD11b and ETP showed no significant changes or differences between all study groups. In contrast, the mean + SD mean fluorescence units (MFI) of CD62P and PAC-1 increased significantly in patients taking PI, indicating an enhanced potential for thrombocyte activation and aggregation.
Conclusion: CD62P expression, detecting the ɑ-platelet degranulation of pro-inflammatory and pro-thrombotic factors and adhesive proteins, and PAC-1 expression, representing a marker for conformation changes of the GIIb/IIIa receptor, increased significantly in patients taking HIV protease inhibitors. The findings of this study revealed a yet unknown pathway of platelet activation, possibly contributing to the increased risk for CVE under HIV protease inhibitor containing cART.
Clinical Trial Registration No.: DRKS00000288.
This paper reflects on legal pluralism. How did medieval societies incorporate both unwritten customs and written law at the same time? How did they constitute the process of finding justice? What is the essense of legal pluralism, and will it help us understand the situation of Taiwan’s indigenous population?
We aim to solve these problems by taking a closer look at medieval Saxony: for around 400 years, both laws given by the authorities and traditional customs in Saxony worked fine in parallel. The latter were put into writing by the legal practitioner Eike von Repgow around 1230 for reasons unknown. We refer to his collection of laws and customs of the Saxons as the Sachsenspiegel ("Mirror of Saxons").
While Saxons certainly differed from Taiwan’s indigenous population for many reasons, such as the supposedly weaker egalitarianism among the Saxons than among at least some indigenous groups, the two show some remarkable similarities nonetheless. Just like the Taiwanese Gaya, the Sachsenspiegel’s spiritual origin raises the claim to validity. Furthermore, comparing the handling of a person’s sale of inherited property, the legal situations in the Sachsenspiegel and Taiwan’s unwritten customs resemble each other. The heir can transfer only property he acquired personally. Furthermore, the author discusses the different character of courts and procedure under oral law in contrast to written modern law.
Finally, the paper concludes with some remarks about a learned commentary on the Sachsenspiegel written around 1325, combined with an outlook on the possible future of Taiwanese customs.
Ob eine Suche nach Rechtsbegriffen des Mittelalters förderlich sei, erscheine – so Harald Siems – zweifelhaft. Theoretische Reflexionen über Recht habe man im Frühen Mittelalter kaum angestellt. Jedenfalls nicht in der Intensität, dass sie sich zum Begriff verdichtet hätten. Die Frage nach dem Rechtsbegriff sei auch deshalb fehl am Platze, weil im Frühmittelalter so etwas zur Lösung von Rechtsfragen nichts hätte beitragen können. Warum sollte jemand auf die Idee kommen, "quasi auf Vorrat" Rechtsbegriffe zu entwickeln? Schon wenn es um konkrete Rechtsfragen wie beispielsweise die Behandlung von Diebstahl oder Raub geht, fehle es "noch lange an Begriff und System". Diese knappe Feststellung bringt Siems’ Ausführungen für einen kurzen Moment in die Nähe von Überlegungen, die Pilch anstellt und die auf dieser Tagung zu verfolgen sind. Aber wirklich nur für einen Augenblick blitzt das auf: Siems sagt, Rechtsbegriffe seien eine schwierige, abstrakte Kategorie, für die heute die Vertreter der Rechtstheorie und der Rechtsphilosophie zuständig seien. ...
The effect of a single site mutation of Arg-54 to methionine in Paracoccus denitrificans cytochrome c oxidase was studied using a combination of optical spectroscopy, electrochemical and rapid kinetics techniques, and time-resolved measurements of electrical membrane potential. The mutation resulted in a blue-shift of the heme a alpha-band by 15 nm and partial occupation of the low-spin heme site by heme O. Additionally, there was a marked decrease in the midpoint potential of the low-spin heme, resulting in slow reduction of this heme species. A stopped-flow investigation of the reaction with ferrocytochrome c yielded a kinetic difference spectrum resembling that of heme a(3). This observation, and the absence of transient absorbance changes at the corresponding wavelength of the low-spin heme, suggests that, in the mutant enzyme, electron transfer from Cu(A) to the binuclear center may not occur via heme a but that instead direct electron transfer to the high-spin heme is the dominating process. This was supported by charge translocation measurements where Deltapsi generation was completely inhibited in the presence of KCN. Our results thus provide an example for how the interplay between protein and cofactors can modulate the functional properties of the enzyme complex.
Background and Purpose: Activation of hepatic thyroid hormone receptor β (THR-β) is associated with systemic lipid lowering, increased bile acid synthesis, and fat oxidation. In patients with non-alcoholic steatohepatitis (NASH), treatment with THR-β agonists decreased hepatic steatosis and circulating lipids, and induced resolution of NASH. We chose resmetirom (MGL-3196), a liver-directed, selective THR-β agonist, as a prototype to investigate the effects of THR-β activation in mice with diet-induced obesity (DIO) and biopsy-confirmed advanced NASH with fibrosis.
Experimental Approach: C57Bl/6J mice were fed a diet high in fat, fructose, and cholesterol for 34 weeks, and only biopsy-confirmed DIO-NASH mice with fibrosis were included. Resmetirom was administered at a daily dose of 3 mg·kg−1 p.o., for 8 weeks. Systemic and hepatic metabolic parameters, histological non-alcoholic fatty liver disease (NAFLD) activity and fibrosis scores, and liver RNA expression profiles were determined to assess the effect of THR-β activation.
Key Results: Treatment with resmetirom did not influence body weight but led to significant reduction in liver weight, hepatic steatosis, plasma alanine aminotransferase activity, liver and plasma cholesterol, and blood glucose. These metabolic effects translated into significant improvement in NAFLD activity score. Moreover, a lower content of α-smooth muscle actin and down-regulation of genes involved in fibrogenesis indicated a decrease in hepatic fibrosis.
Conclusion and Implications: Our model robustly reflected clinical observations of body weight-independent improvements in systemic and hepatic metabolism including anti-steatotic activity.
Do sentido interno
(2009)
Religion und Gesellschaft
(2016)
Abstract
Indoor air pollution with harmful particulate matter (PM) is mainly caused by cigarette smoke. Super-Slim-Size-Cigarettes (SSL) are considered a less harmful alternative to King-Size-Cigarettes (KSC) due to longer filters and relatively low contents. We ask if “Combined Mainstream and Sidestream Smoke” (CMSS)-associated PM levels of SSL are lower than of KSC and thus are potentially less harmful. PM concentrations in CMSS (PM10, PM2.5, and PM1) are measured from four cigarette types of the brand Vogue, using an “automatic-environmental-tobacco-smoke-emitter” (AETSE) and laser aerosol spectrometry: SSL-BLEUE, -MENTHE, -LILAS and KSC-La Cigarette and -3R4F reference. This analysis shows that SSL MENTHE emitted the highest amount of PM, and KSC-La Cigarette the lowest. 3R4F reference emitted PM in the middle range, exceeding SSL BLEUE and falling slightly below SSL LILAS. It emerged that PM1 constituted the biggest proportion of PM emission. The outcome shows significant type-specific differences for emitted PM concentrations. Our results indicate that SSL are potentially more harmful for passive smokers than the respective KSC. However, this study cannot give precise statements about the general influence of the size of a cigarette on PM. Alarming is that PM1 is responsible for the biggest proportion of PM pollution, since smaller particles cause more harmful effects.
The genus Sibogasyrinx has to date included only four species of rare deep-water Conoidea, each known from few specimens. In shell characters it strongly resembles three distantly-related genera, two of which, Comitas and Leucosyrinx, belong to a different family, the Pseudomelatomidae. A molecular phylogenetic analysis of a large amount of material of Conoidea has revealed the existence of much additional undescribed diversity within Sibogasyrinx from the central Indo-Pacific and temperate Northern Pacific. Based on partial sequences of the mitochondrial cox1 gene and morphological characters of 54 specimens, 10 species hypotheses are proposed, of which six are described as new species: S. subula sp. nov., S. lolae sp. nov., S. maximei sp. nov., S. clausura sp. nov., S. pagodiformis sp. nov. and S. elbakyanae Kantor, Puillandre & Bouchet sp. nov. One of the previously described species was absent in our material. Most of the new species are very similar and are compared to Leucosyrinx spp. Species of Sibogasyrinx are unique among Conoidea on account of the high intrageneric variability in radular morphology. Three distinct radula types are found within Sibogasyrinx, two of which are confined to highly supported subclades.
The status of five genera recognized within subfamily Buccininae (Buccinidae) is critically re-assessed based on the molecular phylogenetic analysis of the cox-1, 16S, and 28S gene fragments. Our results suggest restoring Volutharpa P. Fischer, 1856 from synonymy of Buccinum and we also consider Plicibuccinum Golikov & Gulbin, 1977 as valid genus. New molecular data provide further support for the synonimization of Bathybuccinum Golikov & Sirenko, 1988 with Buccinum Linnaeus, 1758. Furthermore, our data demonstrate that Thysanobuccinum Golikov #38; Gulbin in Golikov, 1980 and Ovulatibuccinum Golikov & Sirenko, 1988 as currently construed are nested within Buccinum and their subgeneric rank is not confirmed. Therefore, we synonymize these genera with Buccinum. In the absence of molecular data the monotypic genus Corneobuccinum Golikov & Gulbin, 1977 is provisionally considered valid. Two new species, Buccinum hasegawai sp. nov. and B. bizikovi sp. nov. are described from the Kurile Islands; these species were previously erroneously identified as Bathybuccinum bombycinum (Dall, 1907) and Ovulatibuccinum ovulum (Dall, 1907), respectively. New replacement names are proposed for the secondary junior homonym Buccinum perlatum (Fraussen & Chino, 2009) and the primary junior homonyms Buccinum coronatum Golikov, 1980 and Buccinum costatum Golikov 1980.
Die kulturhistorische Forschung hat Gertrud Kantorowicz (1876-1945) - anders als ihren Cousin, den berühmten Mediävisten Ernst Kantorowicz - nur gelegentlich beachtet. Dabei hat die Simmel-Vertraute, promovierte Kunsthistorikerin und wohl einzige Dichterin des George-Kreises ein nicht unbeträchtliches Werk hinterlassen, darunter etwa eine bislang nicht gewürdigte Reihe von Michelangelo-Nachdichtungen und die bedeutende Übersetzung von Bergsons "L'évolution créatrice".
Wie nehmen Sie die Goethe-Universität heute in Zeiten des stärkeren nationalen und internationalen Wettbewerbs der Hochschulen wahr?
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Objective. Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.
Measurements and Main Results. Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.
Conclusions. This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.
Die Flechte Cladonia stygia (Fr.) Ruoss wurde anlässlich einer Bestandsaufnahme der Rentierflechten 2009 erstmals aus Hessen gemeldet. Da die Unterscheidung von der ähnlichen C. rangiferina (L.) F. H. Wigg. anhand morphologischer Merkmale oft unsicher ist, wurden molekulargenetische Daten zur Identifizierung der hessischen Belege der Art herangezogen. Phylogenetische Stammbäume auf der Grundlage von sechs mitochondrialen und nuklearen Genloci untermauern die Abgrenzung beider Arten. Nur zwei von sieben gemeldeten hessischen Vorkommen gehören nach diesen Ergebnissen zu C. stygia, die übrigen zu C. rangiferina. Eine gezielte Suche nach C. stygia und eine durch molekulargenetische Daten untermauerte Bestimmung der Belege erscheint notwendig, um den Status der Art in Hessen zuverlässig beurteilen zu können.
Anlass für diese molekular-genetische Studie war der Verdacht, dass die seit 1986 bekannten und seitdem stark expandierten Populationen des Zwerg- Sonnenröschens (Fumana procumbens) im Naturschutzgebiet "Scheid bei Volkmarsen" in Nordhessen angesalbt wurden. Die Art war zuvor aus Nordhessen nicht gemeldet; lediglich in Südhessen waren isolierte Vorkommen auf kalkreichen Sanddünen bekannt. Eine Split-Netzwerk-Analyse basierend auf AFLP-Profilen von 69 Individuen an acht Lokalitäten konnte aufdecken, dass sich die südhessischen und französischen Populationen im Netzwerk jeweils klar als eigene Gruppen abgrenzen, während sich die nordhessischen Individuen mit den thüringischen, sachsen-anhaltinischen und gotländischen Aufsammlungen mischen. Die Frage nach der Ansalbung der Bestände lässt sich durch die Studie nicht beantworten. Wurde angesalbt, dann stammte das Ausgangsmaterial höchstwahrscheinlich aus den östlich sich anschließenden Populationen.
Za svojega kratkoga boravka u Petrogradu 1912. I. Milcetic; opisao je bogatu Bercicevu zbirku glagoljickih rukopisa i tiskanih knjiga iz Ruske nacionalne knjižnice, ali nije stigao podrobno prouciti svaki sastavni dio Berciceve grade. U Milceticevu opisu kodeksa br. 1 (Klimantovicev zbornik, 1514.) spominje se prolog Muke, ali se ne upozorava da se u nastavku toga prologa nalazi ulomak iz srednjovjekovnoga prikazanja sa scenom Judine izdaje Isusa. Ta je scena u srednjem vijeku ponajviše uznemiravala puk jer se tada od svega najviše mrzila laž, izdaja i prijetvornost. U radu se opisuju i prvi put objavljuju ulomci nepoznate redakcije Muke Isuhrstove iz petrogradske Berciceve zbirke (sign. Bc 1), koji predstavljaju za sada najstariji zapisani prolog i scenu hrvatskoga srednjovjekovnoga prikazanja pasionske tematike. Stihovi ulomaka usporeduju se s mladom ciklickom Mukom Spasitelja našega iz glagoljickoga Zbornika prikazanja (1556.), s kojom se u korpusu hrvatskoga srednjovjekovnoga pjesništva ti ulomci najviše podudaraju.
Reconstructions of the vegetation of Europe during the Last Glacial Maximum (LGM) are an enigma. Pollen-based analyses have suggested that Europe was largely covered by steppe and tundra, and forests persisted only in small refugia. Climate-vegetation model simulations on the other hand have consistently suggested that broad areas of Europe would have been suitable for forest, even in the depths of the last glaciation. Here we reconcile models with data by demonstrating that the highly mobile groups of hunter-gatherers that inhabited Europe at the LGM could have substantially reduced forest cover through the ignition of wildfires. Similar to hunter-gatherers of the more recent past, Upper Paleolithic humans were masters of the use of fire, and preferred inhabiting semi-open landscapes to facilitate foraging, hunting and travel. Incorporating human agency into a dynamic vegetation-fire model and simulating forest cover shows that even small increases in wildfire frequency over natural background levels resulted in large changes in the forested area of Europe, in part because trees were already stressed by low atmospheric CO2 concentrations and the cold, dry, and highly variable climate. Our results suggest that the impact of humans on the glacial landscape of Europe may be one of the earliest large-scale anthropogenic modifications of the earth system.
Im nordwestlichen Westfalen und der Grafschaft Bentheim wurde eine Bestandserhebung von Hypericum elodes durchgeführt. Mit Vorkommen an etwa 50 Gewässern dürfte diese Art innerhalb der Bundesrepublik Deutschland in der untersuchten Region ihren Verbreitungsschwerpunkt besitzen. Aspekte der Bestandsschwankungen und Gefährdung werden diskutiert.
In den Jahren 1986 bis 1990 wurde Ranunculus ololeucos (Reinweißer Hahnenfuß) im nordwestlichen Westfalen und südöstlichen Niedersachsen an 17 Gewässern beobachtet. Einen Verbreitungsschwerpunkt bildet der Naturraum "Gildehauser Venn". Ursache für viele Neu- und Wiederfunde dürfte der für Ranunculus ololeucos günstige Witterungsverlauf der letzten Jahre mit mehreren trockenen Sommerhalbjahren gewesen sein. Noch stärker als durch Eutrophierung erscheint die Art wie auch andere Littorelletea-Arten durch die zunehmende Versauerung der nährstoffarmen Stillgewässer gefährdet.
Vom Pillenfarn sind im Untersuchungsgebiet 22 aktuelle Fundorte bekannt; einen Verbreitungsschwerpunkt besitzt er im westfälisch-niedersächsischen Grenzgebiet, im Bereich des Gildehauser Venns und der Brechte. Der Pillenfarn besiedelt heute fast ausschließlich neu angelegte, meist nährstoffärmere, schwach saure bis neutrale, aber auch schwach basische Gewässer. Vorkommen an natürlichen Heideweihern (Witte Venn, Gildehauser Venn) sind heute erloschen. Wichtigste Ursache hierfür dürfte die Gewässerversauerung der letzten Jahrzehnte sein. Wasseranalysen ergaben bei einigen Faktoren recht uneinheitliche Werte. Insbesondere fielen bei einzelnen (z. T. belasteten) Gewässern erhöhte Stickstoff- und Calciumwerte auf. Unter optimalen Bedingungen bildet der Pillenfarn in dichten Rasen wachsend die Pillenfarn-Gesellschaft (Pilularietum globuliferae). Die Ausbildung von kennartenarmen und kennartenreichen Beständen dürfte vor allem auf die floristische Ausstattung des Standortes und seiner näheren Umgebung bei Anlage der Gewässer zurückzuführen sein. Die aus der Abb. 3 ersichtliche Vegetationszonierung kann als typisch für viele nährstoffärmere Pioniergewässer der nordwestdeutschen Sandgebiete angesehen werden.
Die im Gebiet des mittleren Teutoburger Waldes auftretenden Sedimentationsanomalien der turbiditischen "Rothenfelder Grünsande" und der "submarinen Großgleitung im Raum Halle" werden in das Ober-Turon gestellt und feinstratigraphisch neu gedeutet. Dabei können die "Rothenfelder Grünsande" erstmals mit einer Lage im Steinbruch Foerth, Halle/ Westf., nachgewiesen werden. Unbekannt war auch bisher das Vorkommen einer submarinen Gleitung im Steinbruch Anneliese, Bad Laer, in der ein weiterer Turbidit eingeschaltet ist. Die turbiditischen Rothenfelder Grünsande gehören lithostratigraphisch in die hohe "Untere Plänerkalk-Einheit (Iower limestone unit)" (ERNST& WOOD& RASEMANN 1984), biostratigraphisch in die untere Subprionocyclus normalis - Ammonitenzone und in die untere Inoceramus aff. frechi & Inoceramus cf. websteri - Inoceramen-Faunenzone. Eventstratigraphisch sind sie durch ihre Lage von einigen Metern über dem Tuff F und dem Micraster-Event gekennzeichnet. Die Untergrenzen der submarinen Gleitungen von HalielWestf. und vom Steinbruch Anneliese, Bad Laer, befinden sich lithostratigraphisch in der "Grauweißen Wechselfolge" (WOOD& ERNST& RASEMANN 1984). Im Steinbruch Foerth, HalLe/Westf., liegt die Basis der submarinen Gleitungen nur knapp über dem Beginn der Grauweißen Wechselfolge. In den verrutschten Gesteinsmassen läßt sich eine stratigraphische Abfolge vom hohen Ober-Turon bis in das Mittel-Coniac erkennen. Die Basis der submarinen Gleitung von Bad Laer liegt einige Meter höher als in HalielWestf. Ihre Mächtigkeit beträgt nur 5 m im Gegensatz zu der weit über 100 m mächtigen Rutschung von Halle/Westf.
Germany’s educational system has undergone a series of transformations during the last 40 years. In recent years, marked increases in enrolment have occurred. In response, admission requirements have been relaxed and new universities have been established. Academic distance education in the former Federal Republic of Germany (West Germany) was ushered in by the educational radio broadcasts around the end of the 1960s. Aside from the formation of the FernUniversität (Open University) in West Germany in 1975, there were significant developments in distance education occurring at the major universities in the German Democratic Republic (East Germany). After German reunification in 1990, the new unitary state launched programs to advance the development of distance education programs at conventional universities. Germany’s campus-based universities (Präsenzuniversitäten) created various entities, including central units and consortia of universities to design and market distance education programs. Hybridisation provides the necessary prerequisites for dual mode delivery, such as basic and continuing education programs, as well as for the combination of distance and campus-based education (Präsenzstudium). Hybridisation also has also opened the door for the creation of new programs. Following an initial phase in which distance education research is expected to centralize a trend towards decentralisation is likely to follow. The German Association for Distance Education (AG-F) offers a viable research network in distance education. Two dual mode case studies are also be surveyed: The Master of Arts degree, offered by the University of Koblenz-Landau, with Library Science as the second major, and the University of Kaiserslautern, where basic education will continue to be captured within the domain of the Präsenzstudium or campus-based education. The area in which distance education is flourishing most is within the field of academic continuing education, where external experts and authors are broadening the horizon of the campus. Multimedia networks will comprise the third generation of distance education.
RNA interference (RNAi) has emerged as a powerful tool to induce loss-of-function phenotypes by post-transcriptional silencing of gene expression. In this study we wondered whether inducible RNAi-cassettes integrated into cellular DNA possess the power to trigger neoplastic growth. For this purpose inducible RNAi vectors containing tetracycline (Tet)-responsive derivatives of the H1 promoter for the conditional expression of short hairpin RNA (shRNA) were used to target human polo-like kinase 1 (Plk1), which is overexpressed in a broad spectrum of human tumors. In the absence of doxycycline (Dox) HeLa clones expressing TetR, that carry the RNAi-cassette stably integrated, exhibited no significant alteration in Plk1 expression levels. In contrast, exposure to Dox led to marked downregulation of Plk1 mRNA to 3% and Plk1 protein to 14% in cell culture compared to mismatch shRNA/Plk1-expressing cells. As a result of Plk1 depletion cell proliferation decreased to 17%. Furthermore, for harnessing RNAi for silencing disease-related genes in vivo we transplanted inducible RNAi-HeLa cells onto nude mice. After administration of Dox knockdown of Plk1 expression was observed correlating to a significant inhibition of tumor growth. Taken together, our data revealed that genomically integrated RNAi-elements are suitable to hamper tumor growth by conditional expression of shRNA.
The interaction of fibroblast growth factors (FGFs) with their fibroblast growth factor receptors (FGFRs) are important in the signaling network of cell growth and development. SSR128129E (SSR),[1, 2] a ligand of small molecular weight with potential anti-cancer properties, acts allosterically on the extracellular domains of FGFRs. Up to now, the structural basis of SSR binding to the D3 domain of FGFR remained elusive. This work reports the structural characterization of the interaction of SSR with one specific receptor, FGFR3, by NMR spectroscopy. This information provides a basis for rational drug design for allosteric FGFR inhibitors.
Music is an effective means of stress-reduction. However, to date there has been no systematic comparison between musical and language-based means of stress reduction in an ambulatory setting. Furthermore, although the aim for listening to music appears to play a role in its effect, this has not yet been investigated thoroughly. We compared musical means, language-based means like guided relaxation or self-enhancement exercises, and a combination of both with respect to their potential to reduce perceived stress. Furthermore, we investigated whether the aim one wants to achieve by listening to these means had an impact on their effect. We tested 64 participants (age: M = 40.09 years; 18 female) for 3–10 days during their everyday life using an app containing three means: musical means, language-based means, and a combination of both. For the music and the combination conditions participants were asked to select an aim: relaxation or activation. We measured perceived stress, relaxation, activation, and electrical skin resistance (ESR) as a marker of sympathetic nervous system (SNS) activity before and after using the app. Participants were instructed to use the app as often as desired. Overall, perceived stress was reduced after using the app, while perceived relaxation and activation were increased. There were no differences between the three means regarding their effect on perceived stress and relaxation, but music led to a greater increase in ESR and perceived activation compared to the other means. There was a decrease in ESR only for music. Moreover, perceived stress was reduced and perceived relaxation was increased to greater extent if the aim “relaxation” had been selected. Perceived activation, however, showed a larger increase if the aim had been “activation,” which was even more marked in the case of music listening. Our results indicate that all three means reduced perceived stress and promoted feelings of relaxation and activation. For enhancing feelings of activation music seems to be more effective than the other means, which was reflected in increased SNS activity as well. Furthermore, the choice of an aim plays an important role for the reduction of stress, and promotion of relaxation and activation.
The COVID-19 pandemic has caused strains on health systems worldwide disrupting routine hospital services for all non-COVID patients. Within this retrospective study, we analyzed inpatient hospital admissions across 18 German university hospitals during the 2020 lockdown period compared to 2018. Patients admitted to hospital between January 1 and May 31, 2020 and the corresponding periods in 2018 and 2019 were included in this study. Data derived from electronic health records were collected and analyzed using the data integration center infrastructure implemented in the university hospitals that are part of the four consortia funded by the German Medical Informatics Initiative. Admissions were grouped and counted by ICD 10 chapters and specific reasons for treatment at each site. Pooled aggregated data were centrally analyzed with descriptive statistics to compare absolute and relative differences between time periods of different years. The results illustrate how care process adoptions depended on the COVID-19 epidemiological situation and the criticality of the disease. Overall inpatient hospital admissions decreased by 35% in weeks 1 to 4 and by 30.3% in weeks 5 to 8 after the lockdown announcement compared to 2018. Even hospital admissions for critical care conditions such as malignant cancer treatments were reduced. We also noted a high reduction of emergency admissions such as myocardial infarction (38.7%), whereas the reduction in stroke admissions was smaller (19.6%). In contrast, we observed a considerable reduction in admissions for non-critical clinical situations, such as hysterectomies for benign tumors (78.8%) and hip replacements due to arthrosis (82.4%). In summary, our study shows that the university hospital admission rates in Germany were substantially reduced following the national COVID-19 lockdown. These included critical care or emergency conditions in which deferral is expected to impair clinical outcomes. Future studies are needed to delineate how appropriate medical care of critically ill patients can be maintained during a pandemic.
1881 Viyana doğumlu olan Stefan Zweig, savaş ortamını bizzat yaşamış ve eserlerinde daima savaş karşıtı bir tutum sergilemiştir. Zweig'ın tek isteği, yaşanılan savaş sonrasında, insanların huzuru ve barışı yakalamasıdır. 1938-1942 yılları arasında Brezilya'da sürgündeyken kaleme aldığı "Satranç" adlı son eseri de göstermek istediği değerler açısından büyük bir öneme sahiptir. Zweig, insan ruhunun derinliklerine inerek, betimlemelerle ve benzetmelerle Nazizm'in/ Nazi Almanya'sının ülke ve insanlar üzerinde bıraktığı sosyal ve psikolojik etkileri yansıtmaya çalışır. Savaşın insanlığı getirdiği noktada, yazarın intiharından önce bıraktığı bir veda mektubu niteliği taşıyan bu eserde, Hitler iktidarının toplama kamplarının haricinde aydınlar için kullandığı başka bir yönteme dikkat çekilir. Zweig'e göre kullanılan bu yöntem, belki de toplama kamplarındaki insanların yaşadıklarından bile daha ağır bir zulümdür.
Alman Edebiyatı'nda önemli bir yere sahip olan Stefan Zweig, "Satranç" adlı eserinde, satranç oyunu üzerinden, yaşanılan tüm olumsuzluklara rağmen savaş döneminde bireylerin ayakta kalma/ var olmaya çalışma süreçlerini aktarır. Otobiyografik özellik gösteren eserde, savaş döneminde Naziler tarafından tutuklandıktan sonra yersiz-yurtsuzluğa mahkûm edilen bir karakterle, dünya satranç şampiyonu olan bir karakterin satranç mücadelesi ele alınır. 20. yüzyılın acımasızlığı gözler önüne serilirken, tarihsel olayların bıraktığı izlere ve o izlerle yaşamaya çalışmanın ne demek olduğuna yakından tanık olmak mümkündür. Bu çalışmada, eserden hareketle (metne bağlı/werkimmanent yaklaşımla) Nasyonal Sosyalizmin toplumda ve insanlar üzerinde bıraktığı izler, yarattığı yıkımlar ve Nasyonal Sosyalizm dönemi aktarılmaya çalışılmıştır.
Zeitgenössische autobiographische Textauszüge dienen als eine gute Inspiration zum biographischen Schreiben, denn in ihnen begegnen dem Leser Themen wie Kindheit, Jugend, Schule, Reisen, Stadt, Heimatort. Diese Ich-Geschichten sind erinnernd, beschreibend, berichtend und erzӓhlend. Das Ziel dieser Arbeit ist es darzulegen, inwieweit ein Portfolioeinsatz einen Beitrag bzw. eine Anregung zum Schreiben über eigene Lebenserfahrungen anhand von beschreibenden, berichtenden und erzählenden Aufzeichnungen von Erinnerungen zu leisten vermag. Durch das Lesen von Auszügen autobiographischer Texte erlangen die Studierenden grundlegende Kenntnisse über die Funktion von beschreibenden, berichtenden und erzӓhlenden Darstellungsweisen und nutzen diese bei der schriftlichen Darstellung ihrer eigenen Erlebnisse und Erfahrungen. Insgesamt wird nicht nur die Dokumentation der eigenen Schreibprodukte, sondern auch die inhaltliche sowie formale Gestaltung des Schreib-Portfolios für die Produktion von biographischen Texten als wirksam angesehen. Die Studierenden sahen sich in ihrem handwerklichen Tun bei der Produktion eigener autobiographischer Texte bestӓrkt und ermutigt.
Fremdsprachige Literatur impliziert bei Lernenden durchaus noch große Berührungsängste auch im fortgeschrittenen Stadium. Im Sinne einer sprachlichen und kulturellen Bildung sollte auf die Lektüre in der Originalsprache keinesfalls verzichtet werden. So wird insbesondere im deutschen Kulturraum das Vorlesen als Grundlage zur Entwicklung von Lesemotivation und Lesesozialisation eingesetzt. Das Vorlesen trägt in besonderer Weise zur Bildung, zur Sprachentwicklung, zur Aneignung der Kommunikations- und Ausdrucksfähigkeit bei. Durch Vorlesen kann der Zugang zur Literatur unterstützt und in unterschiedlichen Bildungsphasen gefördert werden. Untersuchungen haben nachgewiesen, dass das Vorlesen positive Auswirkungen auf die Lesemotivation und im Anschluss auf die Lesekompetenz haben kann. Wesentlich sind hier u.a. das Wissen der Lehrperson um die unterschiedlichen Vorlesephasen, sowie die Textauswahl. In diesem Beitrag geht es um die Relevanz des Vorlesens bei der Leseförderung im DaF/DaZ-Bereich, somit in der sprachlichen und kulturellen Bildung. Als Ausgangspunkt dient in diesem Kontext ein Blick auf die Vorlesetradition in der türkischen und deutschen Gesellschaft, um auf die unterschiedlichen Entwicklungen in der Vorlesekultur hinzuweisen. In diesem Rahmen liegt der Fokus auf der Frage: Wie kann die Literalität im Fremdsprachenunterricht eingesetzt werden, um das Erlernen einer Sprache zu unterstützen? Darauf aufbauend werden Erfahrungen von Lehrpersonen und empirische Ergebnisse zum Vorlesen in der deutschen Gesellschaft thematisiert und erlӓutert und einige Konzepte vorgestellt. Ausgehend davon werden schließlich Überlegungen und Möglichkeiten für die Praxis, sowie konkrete Tipps zur Umsetzbarkeit im DaF/ DaZ-Bereich am Beispiel von Uwe Timms Kinderroman "Die Zugmaus" diskutiert. In diesem Roman nimmt eine Maus die Leser auf eine Reise durch unterschiedliche Länder mit. Dadurch ist das Buch abwechslungsreich und spannend zugleich und zum Vorlesen besonders geeignet. Dies kann als Zeichen dafür gewertet werden, dass das Vorlesen als Leseförderungsmaßnahme für Jugendliche und junge Erwachsene auch im Studium Freude bereiten kann.
Begegnung mit orientalischer Kultur und orientalischen Denkmustern in den Romanen von Rafik Schami
(2018)
Rafik Schami gehört zu den Autoren mit Migrationserfahrung, und als solcher stellt er in seinem literarischen Schaffen den Blick des Deutschen (Okzidentalen) und den Blick des Orientalen auf die jeweils andere Kultur dar. Ziel der Untersuchung ist es, herauszufinden, wie Rafik Schami den Orient in seinen Romanen verarbeitet. Ferner wird versucht Antworten auf folgende Fragen zu finden: Welche kulturellen Aspekte werden in den für die Untersuchung ausgewählten Romanen reflektiert? Welche Erfahrungen werden in Bezug auf die kulturelle Fremdheit gemacht? In unserem Fall geht es um eine kontrastive Betrachtung der orientalischen Kultur und der westlichen Kulturen. Die Leser Schamis werden mit zwei Wertesystemen konfrontiert, was unwillkürlich zu einer Auseinandersetzung mit kulturellen Unterschieden führt. Dem Autor gelingt damit ein gesteigertes Interesse beim Leser zu erzielen sowie Verständnis und Sensibilität gegenüber beiden Kulturen zu wecken. Die für die Untersuchung herangezogenen Romane von Rafik Schami wurden nach dem hermeneutischen Ansatz und der werkimmanenten Methode im Rahmen literatur- und kulturwissenschaftlicher Theorien analysiert.
Als einer der wesentlichen und natürlichen Bestandteile der sprachlichen Kompetenz weisen Kollokationen sowohl in alltäglichen als auch in formellen Kommunikationssituationen einen elementaren Stellenwert auf. Für die Fremdsprachenlerner machen diese vorgeformten Mehrworteinheiten Produktionsschwierigkeiten aus, da sie in den meisten Fällen zahlreiche strukturelle und semantische Unterschiede zwischen Mutter- und zu lernender Fremdsprache aufweisen. Bei der Sprachproduktion neigen die Lerner häufig dazu, die Kollokationen in ihrer Muttersprache wörtlich in die Zielsprache zu übertragen, was vor allem im Falle von Divergenzen zu eventuellen Interferenzfehlern führen kann. Aus diesem Grund verdient die kontrastive Erfassung von Kollokationen in fremdsprachendidaktischer Diskussion ein besonderes Interesse. Ausgehend von diesen Diskussionen bezweckt die vorliegende Untersuchung primär, die somatischen Kollokationen im Deutschen und Türkischen im Rahmen der kontrastiven Phraseologie unter die Lupe zu nehmen und im Lichte dieser interlingualen Betrachtung die Äquivalenzbeziehungen zwischen beiden Sprachen in diesem lexikalischen Bereich darzulegen. Von den bei der Analyse beschriebenen Erkenntnissen sollen einige didaktische Folgerungen für türkische Deutschlerner abgeleitet werden.
The purpose of this study was to examine if prosodic patterns in oral reading derived from Recurrence Quantification Analysis (RQA) could distinguish between struggling and skilled German readers in Grades 2 (n = 67) and 4 (n = 69). Furthermore, we investigated whether models estimated with RQA measures outperformed models estimated with prosodic features derived from prosodic transcription. According to the findings, struggling second graders appear to have a slower reading rate, longer intervals between pauses, and more repetitions of recurrent amplitudes and pauses, whereas struggling fourth graders appear to have less stable pause patterns over time, more pitch repetitions, more similar amplitude patterns over time, and more repetitions of pauses. Additionally, the models with prosodic patterns outperformed models with prosodic features. These findings suggest that the RQA approach provides additional information about prosody that complements an established approach.
Crustal structure at the western end of the North Anatolian Fault Zone from deep seismic sounding
(2001)
The first deep seismic sounding experiment in Northwestern Anatolia was carried out in October 1991 as part of the "German - Turkish Project on Earthquake Prediction Research" in the Mudurnu area of the North Anatolian Fault Zone. The experiment was a joint enterprise by the Institute of Meteorology and Geophysics of Frankfurt University, the Earthquake Research Institute (ERI) in Ankara, and the Turkish Oil Company (TPAO). Two orthogonal profiles, each 120 km in length with a crossing point near Akyazi, were covered in succession by 30 short period tape recording seismograph stations with 2 km station spacing. 12 shots, with charge sizes between 100 and 250 kg, were fired and 342 seismograms out of 360 were used for evaluation. By coincidence an M b = 4.5 earthquake located below Imroz Island was also recorded and provided additional information on Moho and the sub-Moho velocity. A ray tracing method orginally developed by Weber (1986) was used for travel time inversion. From a compilation of all data two generalized crustal models were derived, one with velocity gradients within the layers and one with constant layer velocities. The latter consists of a sediment cover of about 2 km with V p » 3.6 km/s, an upper crystalline crust down to 13 km with V p » 5.9 km/s, a middle crust down to 25 km depth with V p » 6.5 km/s, a lower crust down to 39 km Moho depth with V p » 7.0 km/s and V p » 8.05 km/s below the Moho. The structure of the individual profiles differs slightly. The thickest sediment cover is reached in the Izmit-Sapanca-trough and in the Akyazi basin. Of particular interest is a step of about 4 km in the lower crust near Lake Sapanca and probably an even larger one in the Moho (derived from the Imroz earthquake data). After the catastrophic earthquake of Izmit on 17 August 1999 this significant heterogeneity in crustal structure appears in a new light with regard to the possible cause of the Izmit earthquake. Heterogeneities in structure are frequently also heterogeneities in strength and stress that impede or even lock rupture. The Izmit earthquake is discussed in relation to a large stepover or jog at the North Anatolian Fault.
Background The role of the Fcgamma receptor IIa (FcgammaRIIa), a receptor for C-reactive protein (CRP), the classical acute phase protein, in atherosclerosis is not yet clear. We sought to investigate the association of FcgammaRIIa genotype with risk of coronary heart disease (CHD) in two large population-based samples. Methods FcgammaRIIa-R/H131 polymorphisms were determined in a population of 527 patients with a history of myocardial infarction and 527 age and gender matched controls drawn from a population-based MONICA- Augsburg survey. In the LURIC population, 2227 patients with angiographically proven CHD, defined as having at least one stenosis [greater than or equal to]50%, were compared with 1032 individuals with stenosis <50%. Results In both populations genotype frequencies of the FcgammaRIIa gene did not show a significant departure from the Hardy-Weinberg equilibrium. FcgammaRIIa R(-131)->H genotype was not independently associated with lower risk of CHD after multivariable adjustments, neither in the MONICA population (odds ratio (OR) 1.08; 95% confidence interval (CI) 0.81 to 1.44), nor in LURIC (OR 0.96; 95% CI 0.81 to 1.14). Conclusion Our results do not confirm an independent relationship between FcgammaRIIa genotypes and risk of CHD in these populations.
Katerina Karakassi beleuchtet am Beispiel des Briefromans "Leandros" von Panagiotis Soutsos, wie in Griechenland selbst die politischen Wirren und die Belastung durch den Krieg literarisch ihren Niederschlag finden. Das Werk von Panagiotis Soutsos ist in der Hinsicht nicht nur ein Zeugnis der politischen Irrungen und Wirrungen seiner Zeit, sondern auch ein Exemplum der intellektuellen Bemühungen, anhand von abendländischem Gedankengut das Bewusstsein der jungen Nation zu untermauern. Dass dies kein leichtes Unternehmen war, zeigt auch der Briefroman "Leandros", den Panagiotis Soutsos 1834 veröffentlichte und dem dieser Beitrag gewidmet ist. Die Lektüre des Romans, die Karakassi hier vorschlägt, geht davon aus, dass das Werk nicht nur gewissermaßen als Manifest für die Gattung Roman fungieren sollte und somit auf den "modernen Bürger" samt seinen Neurosen als ein bedeutendes Sujet hinwies, sondern auch ein neues "nationales Subjekt" nach den Prämissen der politischen Romantik - wie Carl Schmitt sie später skizzierte - zu konzipieren suchte. Die immanenten Widersprüche der politischen Romantik sind jedoch auch im Roman von Panagiotis Soutsos sichtbar: Sie äußern sich als antinomische Ideologeme, als politischer Opportunismus, als intellektuelle und affektive Ambiguität gegenüber der Zukunft und der Vergangenheit der Nation. Dabei wird der neu gegründete Nationalstaat im Text transzendiert und der leitenden staatstheoretischen Metapher dieser Ära folgend, als eine organische Einheit jenseits des aktuellen politischen Treibens imaginiert. Dass dies letztlich nur eine Fiktion ist, suggeriert nicht nur der Selbstmord des Helden. Der Text verzichtet nämlich gänzlich auf eine Herausgeberfiktion und benennt somit implizit den Ort, in dem die nationale Identität gesichert werden kann: in der Imagination, in der Literatur, in der Kunst.
The development of resistance to chemotherapeutic agents, such as Doxorubicin (DOX) and cytarabine (AraC), is one of the greatest challenges to the successful treatment of Acute Myeloid Leukemia (AML). Such acquisition is often underlined by a metabolic reprogramming that can provide a therapeutic opportunity, as it can lead to the emergence of vulnerabilities and dependencies to be exploited as targets against the resistant cells. In this regard, genome-scale metabolic models (GSMMs) have emerged as powerful tools to integrate multiple layers of data to build cancer-specific models and identify putative metabolic vulnerabilities. Here, we use genome-scale metabolic modelling to reconstruct a GSMM of the THP1 AML cell line and two derivative cell lines, one with acquired resistance to AraC and the second with acquired resistance to DOX. We also explore how, adding to the transcriptomic layer, the metabolomic layer enhances the selectivity of the resulting condition specific reconstructions. The resulting models enabled us to identify and experimentally validate that drug-resistant THP1 cells are sensitive to the FDA-approved antifolate methotrexate. Moreover, we discovered and validated that the resistant cell lines could be selectively targeted by inhibiting squalene synthase, providing a new and promising strategy to directly inhibit cholesterol synthesis in AML drug resistant cells.
Nach dem letzten Germanistikkongress 2009 in Izmir wurde der zwölfte Germanistikkongress unter dem Motto "Migration und kulturelle Diversität" vom 12. bis 14. Mai 2014 an der Universität Kocaeli veranstaltet. Bei der Veranstaltung des Kongresses hat der türkische Germanistenverband GERDER aktiv mitgewirkt. Der DAAD, das Goethe Institut Ankara, das Österreichische Kulturinstitut und das Schweizer Konsulat Istanbul haben zur Organisation des Kongresses beigetragen, indem sie die Einladung von Professoren zu Plenarvorträgen und die Verwirklichung kultureller sowie sozialer Aktivitäten, wie Konzert und Abendessen unterstützen.
Kovid 19 pandemi sürecinin başlamasıyla Türkiye'de üniversitelerdeki her bölüm, derslerini sahip oldukları uzaktan eğitim olanakları çerçevesinde sürdürmek zorunda kalmıştır. Beklenmeyen bu durum, eğitim sürecinde birçok öğretim alanında olduğu gibi Almanca öğretiminde de birçok problemi beraberinde getirmiştir. Bu bağlamda bu çalışmanın amacı pandemi sürecine bağlı olarak uzaktan eğitimin Almanca eğitimine etkilerini Kovid 19 pandemi süreci ve kısıtlamalara ilişkin genel görüşler, alınan eğitimin uzaktan olmasına ilişkin olumlu ve olumsuz görüşler, teknolojik donanım, öğretim etkinlikleri, materyal boyutu, etkileşim, ölçme ve değerlendirme boyutu ve uzaktan eğitim sürecine ilişkin öneriler olmak üzere sekiz tema altında, Almanca öğretmenliği lisans programında öğrenim görmekte olan öğrencilerin deneyimleri ve görüşleri doğrultusunda araştırmaktır. Bu amaca ulaşmak için nitel araştırma deseni kapsamında olgubilim yöntemi kullanılmıştır. Çalışmanın araştırma grubu Muğla Sıtkı Koçman Üniversitesi Eğitim Fakültesi Almanca Öğretmenliği lisans Programında öğrenim gören öğrencilerden oluşmaktadır. Almanca öğretmeni adaylarının uzaktan eğitime ilişkin görüşlerinin belirlenmesi amacıyla veri toplama tekniklerinden biri olan yarı yapılandırılmış görüşme tercih edilmiştir. Araştırmanın tüm verileri çevrimiçi ortamda videokonferans yoluyla yapılan görüşmelerden elde edilen verilerden oluşmaktadır. Görüşme tekniğiyle elde edilen verilerin analiz edilmesinde betimsel analiz kullanılmıştır. Araştırma sonucunda genel olarak uzaktan eğitimin günlük yaşama ve eğitim hayatına olumsuz etkilerinin daha fazla olduğu sonucuna ulaşılmıştır. Elde edilen bulgulardan Almanca öğretmenliği programındaki alan derslerinin uzaktan eğitime uygun olmadığı, uzaktan eğitim yönteminin 4 temel dil becerisini geliştirmede yeterli olmadığı; ancak uzaktan eğitim sürecinin az da olsa alıcı becerileri geliştirdiği; üretimsel becerileri ise geliştirmediği anlaşılmaktadır.
Yabancı dil öğrenim ve öğretim sürecinde birçok problemle karşılaşmaktayız. Bunun birçok nedeni olmasına rağmen en önemli sorunlardan biri de öğrenme malzemesinin öğrenene anlamlı gelmemesi, aktarılmak istenen konuyla öğrenen arasında köprünün kurulamaması ve öğrenenin öğrenme girdisini içselleştirememesidir. Bunun çözümü olarak da ‒ anlamlı bir öğrenmenin gerçekleşebilmesi için ‒ şekil ve işlev arasındaki ilişkiye dikkat edilmelidir, çünkü anlamlı öğrenme malzemeleri, öğrenen açısından büyük bir öneme sahip ve vazgeçilmezdir. Fakat bu durum öğreten için büyük bir sorumluluk ve işyükü anlamına gelmektedir. Çalışmamızda dilbilgisi dersinde şekil ve işlev arasındaki ilişki Konjunktiv (dilek kipi) konusu ele alınıp dilin şekil ve işlev yönü dikkate alınaraköğrenene aktarılmaya çalışıldı. Geleneksel yabancı dil derslerinde genellikle dilbilgisel yapılar, dilin işlevsel yönüne vurgu yapılmaksızın şekil yönüyle öğrenene aktarılmakta ve öğrenme kazanımı, öğrenen tarafından ezberlenmiş dilbilgisel bir yapı olmaktan çıkamamaktadır. Bu durumda öğrenen edindiği dilbilgisel yapıyı ne konuşma becerisine ne de özellikle yazma becerisine aktarabilmektedir. Öğrenen söz konusu yapıyı nerde, hangi durumda ve nasıl kullanacağını anlayamamakla birlikte konuyu içselleştirememektedir. Bu şekilde düzenlenmiş bir ders çıktısı öğrenci açısından yararlı olmaması nedeniyle çağdaş eğitim anlayışıyla örtüşmemektedir.
Çalışmamızda yabancı dil öğrenim ve öğretim sürecinde öncelikle sadece dilin şekilsel yönüne dikkat çekildiği düşüncesinden hareket ettik. Dilbilgisel yapıyı aktarırken öncelikle öğrenende dil bilinci oluşturarak öğrenme malzemesinin işlevinin biçimden önce ön plana çıkarılması gerektiğini göstermek istedik. Dilin şekil yönünün işlev yönünün anlaşılmasını engellemesinin önüne geçilmesi gerektiğini belirterek öğrenme malzemesi kullanımının önemini örneklerle açıklamaya çalıştık.
Bu çalışmada öğrencilerin öğrenmiş oldukları dilbilgisel yapıyı nasıl işlevsel hale getireceği, pasif halde bulunan dilbilgisel yapının nasıl aktif hale getirileceği teorik ve deneysel bağlamda incelenmiştir. Tek tip pasif alıştırmaların yerine aktif alıştırma tiplerinden seçenek sunularak öğrencilerin bu bilgiyi, dört beceriye aktarımı mümkün kılınmaya çalışılmıştır. Çalışmada dört beceri birbirinden soyutlanmış biçimde değil bütünleştirici şekilde ele alınmıştır.
Bu çalışmada deneysel yöntemin 'kontrol gruplu öntest ve sontest deney' deseni kullanılmıştır. Hem nitel hem de nicel boyutları içeren karma bir çalışmadır. Çalışmada eylemsel ve üretimsel yöntemlerin kullanıldığı deney grubundaki öntest ve sontest puanları arasındaki başarı farkının; geleneksel yöntemin uygulandığı kontrol grubundaki başarı farkından anlamlı derecede fazla olduğu görülmüştür (F(1,48)=366,149; p<0,001). Buradan hareketle deney grubundaki öğrencilerin daha fazla ilerleme gösterdiği ve başarılı oldukları sonucuna varılmıştır.
Dilbilgisi dersinin iletişimsel yetinin geliştirilmesi için bir araç olduğu görüşü deneysel ve uygulamalı olarak araştırılmıştır. Yaratıcı, eyleme ve öğrencilerin üretimine dayalı bir dilbilgisi dersi geliştirilerek geleneksel dilbilgisi dersine alternatif ders modelleri geliştirilmiştir.
Ölçme ve değerlendirme birçok alanda olduğu gibi yabancı dil öğretiminde de büyük bir öneme sahiptir. Ölçme işlemi, öğrenciye not vermenin yanı sıra öğretim sürecinin, programın, yöntemin etkililiği gibi birçok amaç için de yapılmaktadır. Öğretim sürecinin etkililiğini belirlemek için ise amaca hizmet eden ölçme araçlarının hazırlanması önemli bir unsurdur. Almanca dilbilgisi dersinin ölçme sürecinde genellikle boşluk doldurma, eşleştirme gibi ölçme teknikleri kullanılmaktadır. Ancak bu özellikteki ölçme araçları, dilin biçimsel yönünün ölçülmesini sağlarken; dilin kullanım yönünü ölçmede yetersiz kalmaktadır. Bu bağlamda bu çalışmanın amacı Almanca dilbilgisi derslerinde etkili bir ölçme ve değerlendirme yapabilmek için kullanılan ölçme araçlarının hangi özelliklere sahip olması gerektiği, ölçme aracı hazırlarken soruların nitelikleri, yapısı, ölçme aracının amaca hizmet etmesi için hangi özelliklere sahip olması gerektiğine ilişkin önerilerde bulunmaktır. Çalışmanın sonucunda ölçme ve değerlendirme sürecine işlevsellik kazandırmak amacıyla alternatif ölçme araçlarının kullanılması gerektiği vurgulanarak Almanca dilbilgisi dersinin ölçme ve değerlendirme aşamasında kullanılabilecek alternatif ölçme ve değerlendirme tekniklerine ilişkin önerilerde bulunulmuştur.
Bureschia serbica sp. nov., is described from a cave in the Stara Planina Mt in Serbia as a second species in the genus. It is a troglobite amphibious species, predominantly aquatic like the nominal species of the genus, Bureschia bulgarica. The new species is adapted to amphibious life in running groundwater, unlike the nominal one that lives in subterranean lakes and ponds. Body structure changes, most noticeable the significant changes in the structure of the mouthparts, as a result of preadaptation in aquatic and amphibious Synocheta, are discussed.
Two new opilionid species from suborder Cyphophthalmi, family Sironidae, Siro franzi Karaman & Raspotnig sp. nov. and Siro ozimeci Karaman sp. nov., from Austria and Croatia respectively, are described and illustrated. Both species show a close relation to two other relict sironid species from the southern and eastern parts of the Alps, Siro valleorum and Siro crassus. All four species are treated here as a monophyletic, alpine group of genus Siro, opposed to the remaining two European sironids, S. rubens and S. carpaticus (palaeoeuropean Siro group). The history of the alpine Siro group parallels the history of a part of the dynamic European archipelago in the Mediterranean Tethys area, which became a part of the Alpine orogeny. Diversification of the alpine Siro group is the result of the orogenic evolution of the Alps, linked to the Austroalpine and South Alpine tectonic units.
Balkan populations of Rafalskia olympica (KULCZYNSKI, 1903) are distinguished as separate subspecies Rafalskia olympica bulgarica ST ARI::GA, 1963 novo stat. Certain novel details of the R. olympica female body structure are presented. It is stated that Metaplatybunus drenskii SILHAVY, 1965 is not a synonym of R. olympica.
A new family of Cyphophthalmi with disjunct Mediterranean distribution, Parasironidae fam. nov., is proposed. The new family comprises four genera and seven species. Cimmerosiro gen. nov., Tirrenosiro gen. nov. and Ebrosiro gen. nov. are described as new genera, and Tirrenosiro axeli gen. et sp. nov., Cimmerosiro krivolutskyi gen. et sp. nov., C. juberthiei gen. et sp. nov. and C. rhodiensis gen. et sp. nov. as new species. Parasironidae stands out by a set of characteristics that we recognize as predominantly plesiomorphic. These characteristics and the present distribution indicate the great age of the family, probably early Mesosoic. We attribute its origin to the western part of the Cimmerian terrane, and its current distribution and diversification of the major clades to geotectonic events during the Mesozoic. Additionally, a new sensory organ (sensilla) has been discovered in Cyphophthalmi. This organ is located on the pedipalp coxae and is believed to have a potential hygroreceptive function.
Leukemia cells reciprocally interact with their surrounding bone marrow microenvironment (BMM), rendering it hospitable to leukemia cell survival, for instance through the release of small extracellular vesicles (sEVs). In contrast, we show here that BMM deficiency of pleckstrin homology domain family M member 1 (PLEKHM1), which serves as a hub between fusion and secretion of intracellular vesicles and is important for vesicular secretion in osteoclasts, accelerates murine BCR-ABL1+ B-cell acute lymphoblastic leukemia (B-ALL) via regulation of the cargo of sEVs released by BMM-derived mesenchymal stromal cells (MSCs). PLEKHM1-deficient MSCs and their sEVs carry increased amounts of syntenin and syndecan-1, resulting in a more immature B-cell phenotype and an increased number/function of leukemia-initiating cells (LICs) via focal adhesion kinase and AKT signaling in B-ALL cells. Ex vivo pretreatment of LICs with sEVs derived from PLEKHM1-deficient MSCs led to a strong trend toward acceleration of murine and human BCR-ABL1+ B-ALL. In turn, inflammatory mediators such as recombinant or B-ALL cell–derived tumor necrosis factor α or interleukin-1β condition murine and human MSCs in vitro, decreasing PLEKHM1, while increasing syntenin and syndecan-1 in MSCs, thereby perpetuating the sEV-associated circuit. Consistently, human trephine biopsies of patients with B-ALL showed a reduced percentage of PLEKHM1+ MSCs. In summary, our data reveal an important role of BMM-derived sEVs for driving specifically BCR-ABL1+ B-ALL, possibly contributing to its worse prognosis compared with BCR-ABL1− B-ALL, and suggest that secretion of inflammatory cytokines by cancer cells in general may similarly modulate the tumor microenvironment.
In der letzten Zeitwende haben sich viele Forscher den neuesten zeitgenössischen Sprachlernmethoden und Techniken für einen effektiveren Sprachunterricht gewidmet. Diese Veränderungstendenzen in Lehr- und Lernpädagogik erfordern in ihrer Umsetzung die individuelle Führung des Lerners. In diesem Zusammenhang entwickeln sich Konzepte der Beratungslehre. Unter diesem Aspekt wurde unter einer 12 Wochen langen, vielseitigen Forscher/Berater-Beobachtung im Studienjahr 2018-2019 eine Aktionsforschung in der Deutschlehrerausbildungsabteilung der Universität Trakya in Edirne durchgeführt. Beabsichtigt wurde dabei, eine institutionell eingerahmte, professionell konzipierte Sprachlernberatung mit Fokus Schreiben zu realisieren. Fernerhin wird in dieser Forschung der Problemfrage, ob DaF-Lerner durch eine individuelle Schreiblernberatung ihren Schreibprozess fördern können, nachgegangen. Die Schreiblernberatungen werden nach einem von der Forscherin eigenständig gestalteten Model durchgeführt. Die Datensammlungen verlaufen zweiteilig quantitativ und qualitativ. Die Resultate der Forschung zeigen, dass von der Sprachlernberatung profitiert wird, diesbezüglich Blockaden und Defizite beim Deutsch Schreiben behoben werden. In diesem weiterführenden Beitrag werden anhand eines Fallballspieles der Forschungsprozess und die Ergebnisse repräsentativ dargelegt.
Why does the schooling gap close while the wage gap persists across country income comparisons?
(2023)
The schooling gap diminishes because the services sector becomes more pronounced for high-income countries, and the paid hours gap closes. Although gender wage inequality persists across country income groups, differences in schooling years between females and males diminish. We assemble a novel dataset, calibrate a general equilibrium, multi-sector, -gender, and -production technology model, and show that gender-specific sectoral comparative advantages explain the paid hours and schooling gap decline from low- to high-income economies even when the wage gap persists. Additionally, our counterfactual analyses indicate that consumption subsistence and production share heterogeneity across both income groups and genders are essential to explain the co-decline of the schooling and paid hours gaps. Our results highlight effective mechanisms for policies aiming to reduce gender inequality in schooling and suggest that the schooling gap decline and the de-invisibilization of female paid work observed in high-income countries are linked by structural sector movements instead of wage inequality reductions.
Ziel dieser Studie ist es, die Identitätsbildung mit der Fremdsprache bei DaF-Lehramtstudierenden anhand eines Stummfilms zu untersuchen. Es wird der Beitrag der Stummfilme und der Lehramtstudierenden mit und ohne Auslandserfahrung zur Identität mit der zu erlernenden Sprache herausgearbeitet. Als Forschungsfragen gelten: 1- Wie handeln die DaF-Lehramtstudierendenmit und ohne Deutschland-Erfahrung ineiner Gruppe? 2- Imitieren die Lehramtstudierenden ohne Deutschland-Erfahrung die Lehramtstudierenden mit Deutschland-Erfahrung? 3- Fördern sie sich gegenseitig in der Fremdsprache? Diese Studie basiert aus der Sicht des symbolischen Interaktionismus auf einer qualitativen, pragmatischen Betrachtungsweise, die die Perspektive der Soziologie in Bezug zur symbolischen Kommunikation, ausgehend von der Betrachtungsweise Meads, in die Fremdsprachenlehre anzuwenden versucht. Während der Vorführung des Stummfilms wurden an bestimmten Stellen des Vorspielens gestoppt und die Kommentare der Studenten aufgenommen. Nach der Durchführung wurde im offenen Plenar nach ihrer Ansicht und ihrer Bildung zur Identität durch die Zielsprache anhand von halbstrukturierten Interviewfragen nachgefragt, inwieweit Stummfilme zur Übernahme der Handlungsweisen der zu erlernenden Sprache und ihrem Selbstbewusstsein beitragen, die durch die symbolische Kommunikation den bestimmten gesellschaftlichen Prozessen entsprechen. Durch diesen Beitrag wird die Bildung der Identität der Fremdsprachenlerner mit der Gesellschaft, deren Sprache sie lernen, dargelegt und sie soll auf weitere qualitative Analysen in der Fremdsprachenlehre als Grundlage dienen können.
Uzaktan eğitim yaklaşık 200 sene önce mektup aracılığı ile yapılan steno dersleriyle başlamış olsa da kavramın sistematik olarak eğitimde uygulanması teknolojinin gelişmesiyle paralellik gösterir. Yüz yüze eğitimin belirli bir zamanı, mekânı gerektirmek gibi bazı sınırlılıkları vardır. Yeni medyanın insanların hayatına girmesi ile iletişimin şeklinin değişmesi, bilim insanlarının uzaktan eğitime ilgisini arttırmıştır. Çünkü teknolojik ilerlemeler eğitim sistemini kökten değiştirebilecek duruma gelmiştir ve yüz-yüze eğitimdeki zamana ve mekâna bağlı olma zorunluluğunu ortadan kaldırabilecek potansiyele sahiptir. Bu durum dil öğrenen insanlara daha bireysel ve öz yönetimli öğrenme imkanı sağlar. Uzaktan eğitime dair birçok tanımlama çeşitli kuramlar çerçevesinde yapılmıştır. "Uzaktan Eğitim" teknolojinin sunduğu imkânlar ölçüsünde daima geliştirilmeye açık bir eğitim biçimidir. Bazı ülkeler uzaktan eğitimin önemini daha önce görmüş ve bu konuda yoğun çaba göstermişlerdir. Bu çabalar sonucu uzaktan eğitim, geleneksel eğitime hem bir yol arkadaşı hem de onun ezeli rakibi olabilecek duruma gelmiştir. Bireyselleşme olgusunun gün geçtikçe arttığı ve ortamdan bağımsız öğrenme imkânlarının çok kolaylaştığı 2000'li yıllar eğitimde teknolojiyle bütünleşmiş bir dönüşümü zorunlu hale getirmiştir. Birbiri içine bu denli girmiş çok değişkenli süreçler, eğitim-öğretimde öğrenci ve öğretmenlerin geleneksel görev ve sorumluluklarını da değiştirmektedir. Dil öğrenenlerin kendi başlarına öğrenme ortamlarını düzenleyebilmeleri ve bu ortamlardan verimli şekilde yararlanabilmeleri için sınıf içi ve sınıf dışı öğrenme ortamlarının eğitsel ilkeler açısından düzenlenmesi gerekmektedir. Bu amaca ulaşabilmek için dil öğretimi ile ilgilenen kişilerin özerk öğrenmeyi etkileyen etkenleri ve onların öğretimde nasıl uygulanacağını bilmeleri gerekmektedir. Bu çalışmanın amacı uzaktan eğitim kavramını genel hatları ile tanıtmak, uzaktan eğitimde öğrenci özerkliği kavramının ortaya çıkışını temel kuramlar çerçevesinde incelemek ve bu kapsamda dil öğrenme özerkliğini tartışmaktır.
Although overexpression and hyperactivity of protein kinases are causative for a wide range of human cancers, protein kinase inhibitors currently approved as cancer drugs address only a limited number of these enzymes. To identify new chemotypes addressing alternative protein kinases, the basic structure of a known PLK1/VEGF-R2 inhibitor class was formally dissected and reassembled. The resulting 7-(2-anilinopyrimidin-4-yl)-1-benzazepin-2-ones were synthesized and proved to be dual inhibitors of Aurora A kinase and VEGF receptor kinases. Crystal structures of two representatives of the new chemotype in complex with Aurora A showed the ligand orientation in the ATP binding pocket and provided the basis for rational structural modifications. Congeners with attached sulfamide substituents retained Aurora A inhibitory activity. In vitro screening of two members of the new kinase inhibitor family against the cancer cell line panel of the National Cancer Institute (NCI) showed antiproliferative activity in the single-digit micromolar concentration range in the majority of the cell lines.
In dieser Arbeit soll der Einsatz von Filmen als audiovisuelles Unterrichtsmaterial im Fremdsprachenunterricht erörtert werden. Bei räumlichen und kulturellen Entfernungen zum Zielsprachenland ermöglicht Filmmaterial sprachliche und landeskundliche Inhalte in den Unterricht zu bringen. In diesem Rahmen bieten Filme, die Alltagssprache und Alltagsthemen des Zielsprachenlandes präsentieren, vielfältige Einsatzmöglichkeiten zur Erweiterung der sprachlichen und kulturellen Kompetenzen von Lernenden. Kein anderes Medium verfügt über ein so hohes Potential, die Neugierde der Lerner auf das Zielsprachenland und seine Menschen zu wecken, die Lerner zu motivieren, Emotionen auszulösen und Sprech- und Diskussionsanlässe zu schaffen. Der Einsatz von Filmen leistet einen wichtigen Beitrag zur Gestaltung von effizientem Fremdsprachenunterricht.
Tagungsbericht zu 'Comparative Arts - Neue Ansätze zu einer universellen Ästhetik'. 14. Tagung der DGAVL in Münster, 26. bis 28. November 2008
Unter dem Titel 'Comparative Arts - Ansätze zu einer universellen Ästhetik' veranstaltete die DGAVL vom 26. bis zum 28.11. 2008 in Münster ihre 14. turnusmäßige Tagung.
The HADES experiment provides a large acceptance combined with a high mass resolution and therefore makes it possible to study dielectron and hadron production in heavy-ion collisions with unprecedented precision. With the high statistics of seven billion Au+Au collisions at 1.23 AGeV recorded in 2012 the investigation of collective effects and particle correlations is possible with unprecedented accuracy. We present multi-differential data on directed (v1) and elliptic (v2) flow, and the first measurement of triangular flow (v3), of protons and deuterons.
HADES has a large acceptance combined with a good mass-resolution and therefore allows the study of dielectron and hadron production in heavy-ion collisions with unprecedented precision. With the statistics of seven billion Au-Au collisions at 1.23A GeV recorded in 2012, the investigation of higher-order flow harmonics is possible. At the BEVALAC and SIS18 directed and elliptic flow has been measured for pions, charged kaons, protons, neutrons and fragments, but higher-order harmonics have not yet been studied. They provide additional important information on the properties of the dense hadronic medium produced in heavy-ion collisions. We present here a high-statistics, multidifferential measurement of v1 and v2 for protons in Au+Au collisions at 1.23A GeV.
Die deutsche Literatur ist ohne die Märchen der Gebrüder Grimm nicht zu denken. Sie verkörpern die deutsche Kultur und sind sowohl für Kinder und Jugendliche als auch für Erwachsene geeignet. Neben der Kulturvermittlung von Generation zu Generation haben die Märchen der Gebrüder Grimm den Zweck, das Volk zu belehren und aufzuklären. Die Märchen sind nicht nur in europäischen Ländern gängig, sondern stoßen auch in anderen Ländern wie Georgien, Aserbaidschan und der Türkei auf großes Interesse. Die vorliegende Arbeit hat die Absicht, orientalische Einflüsse in den georgischen, aserbaidschanischen und türkischen Märchenübersetzungen der Gebrüder Grimm zu analysieren und diese zu deuten. Hierfür wird von den Märchen "Rotkäppchen" und "Der Wolf und die sieben Geißlein" Gebrauch gemacht. Parallel dazu werden die Übersetzungen mit der deutschen Ausgangssprache in Vergleich gesetzt und somit sowohl Differenzen als auch Gemeinsamkeiten aufgezeigt.
Background: Ambroxol relieves cough symptoms based on its secretagogue, anti-inflammatory, anti-oxidant, anti-bacterial, anti-viral, immunomodulatory and local anesthetic effects. The present study was designed to explore differential patient profiles and efficacy against acute respiratory symptoms of four formulations registered as over-the-counter medicines.
Methods: Nine hundred sixty-five pharmacy customers purchasing one of four branded ambroxol formulations (extended release capsules, adult syrup, pediatric syrup and soft pastilles) filled a questionnaire including a patient-adapted version of the Bronchitis Severity Scale, several questions on degree of impairment by acute cough, time to onset of symptom relief and duration of treatment. Data on pediatric syrup users were entered by their parents. Based on the exploratory character of the study, no hypothesis-testing statistical analysis was applied.
Results: Users of the pediatric syrup and the pastilles reported somewhat less severe baseline symptoms. The patient-adapted Bronchitis Severity Scale proved feasible as a self-administered tool. Among BSS items, ambroxol formulations improved chest pain while coughing to the largest and sputum to smallest degree (− 75% vs. -40%). Reported efficacy was comparable among formulations with minor differences in favor of the pediatric syrup. Time to onset of symptom relief was less than 60 min in more than 90% of patients and occurred prior to known systemic tmax. Time to onset was the parameter with the greatest differences between formulations, being reported fastest with pastilles and pediatric syrup and, as expected, slowest with extended release capsules. All ambroxol formulations were well tolerated.
Conclusions: We conclude that over-the-counter formulations of ambroxol exhibit comparable user profiles and efficacy. Differences in speed of onset of symptom relief may involve not only those in systemic pharmacokinetics but also local anesthetic effects of immediate release formulations. Differences between pediatric and adult syrup may in part reflect reporting bias.
Background: The objective of the FAVOR study was to evaluate the effect of indacaterol/glycopyrronium (IND/GLY) versus tiotropium on peak forced expiratory volume in 1 s (FEV1) and also to investigate patient satisfaction and treatment preference.
Methods: Patients with moderate-to-severe airflow limitation (FEV1/forced vital capacity ratio of <0.70), those with a COPD assessment test score of ≥10, and those who were maintained on tiotropium HandiHaler® therapy prior to enrollment were recruited for the study, and randomized (1:1) to receive either 4 weeks open-label IND/GLY (110/50 µg) once daily followed by 4 weeks of tiotropium (18 µg) once daily or vice versa. The primary endpoint was FEV1 1 h post-inhalation after 4 weeks of treatment. Other endpoints included patient’s and physician’s preference for treatment, patient’s satisfaction evaluated using a study-specific questionnaire and the abbreviated Treatment Satisfaction Questionnaire for Medication, and safety and tolerability.
Results: Eighty-seven out of 88 randomized patients completed the study and showed significantly higher FEV1 1 h post-inhalation after 4 weeks of treatment with IND/GLY versus tiotropium (treatment difference =0.081 L; p=0.0017). IND/GLY was preferred over tiotropium among the patients (69.4% versus 30.6%, p=0.0004) and the physicians (81.6% versus 18.4%, p<0.0001). A higher proportion of the patients stated they were very satisfied or satisfied with IND/GLY versus tiotropium with regard to dyspnea reduction (79.3% versus 58.0%, respectively) and reduction of dyspnea on exertion (72.4% versus 43.2%, respectively). Patients treated with IND/GLY showed significant improvement in Treatment Satisfaction Questionnaire for Medication domain scores versus tiotropium. IND/GLY demonstrated a good safety and tolerability profile.
Conclusion: This study indicated that, beyond FEV1, important patient-reported outcomes improved with the open-label dual bronchodilator IND/GLY when compared with tiotropium. This study suggests that individual patients felt the lung function benefits with IND/GLY compared with tiotropium, which, in turn, may also have contributed to the preference for IND/GLY.
Purpose: DINO and DACOTA were prospective, noninterventional studies assessing the health status and quality of life of patients with COPD newly treated with roflumilast 500 µg once-daily add-on therapy.
Patients and methods: Patients were evaluated over 6 months. Clinical COPD questionnaire (CCQ) and COPD assessment test (CAT) scores were recorded at baseline and after 3 and 6 months. In DACOTA, post-bronchodilator FEV1 was recorded at each time point.
Results: Of 5,462 and 3,645 patients recruited into DINO and DACOTA, respectively, 3,274 patients in DINO and 916 patients in DACOTA completed the 6-month visit. Almost all patients had severe or very severe airway obstruction; mean baseline CCQ total score was 3.9 in DINO and 3.7 in DACOTA. Overall, 33.8% of patients in DACOTA and 30.6% in DINO discontinued treatment prematurely. Significant and clinically relevant improvements in CCQ total scores were observed in both studies (mean change from baseline of 1.36 in DINO and 0.91 in DACOTA at Month 6 [all P<0.001]). Changes in CAT total score from baseline to Month 6 indicated that the average clinical impact of COPD was reduced from a severe (score: 21–30) to a moderate (score: 11–20) impairment. In DACOTA, mean change in post-bronchodilator FEV1 was 202 mL (P<0.001). Diarrhea, nausea, and weight decrease were the most frequently reported adverse drug reactions.
Conclusion: In real-life clinical practice, roflumilast treatment as an add-on therapy is associated with clinically relevant improvements in health status and quality of life.
Introduction: DACCORD is an observational, non-interventional study being conducted in German primary and secondary care centres. The study aims to describe the impact of disease (including exacerbations) and treatments over 2 years on ‘real-life’ patients with chronic obstructive pulmonary disease (COPD).
Materials and methods: Patients had a clinical and spirometry diagnosis of COPD, were aged ≥40 years and, on recruitment, were initiating or changing COPD maintenance medication. The only exclusion criteria were asthma and randomised clinical trial participation. Exacerbations data were collected every 3 months. COPD medication, COPD Assessment Test (CAT) and forced expiratory volume in 1 s (FEV1) were recorded at baseline and after 1 and 2 years.
Results: A total of 6122 patients were recruited, 3137 (51.2%) of whom completed the 2-year visit. The mean age of these patients was 65.6 years, 59% were male, 69% had mild or moderate airflow limitation, and their mean COPD Assessment Test (CAT) total score was 20.3. Overall, there was a trend towards decreasing COPD exacerbation rates over the 2-year follow-up period, with rates of 0.390 during Year 1 and 0.347 during Year 2. Rates were lower in patients with no exacerbation during the 6 months prior to entry (0.263 and 0.251 during Years 1 and 2, respectively), with 51.6% of patients having no exacerbation during the 6 months prior to entry and over the 2-year follow-up. Approximately 50% of the overall population experienced a clinically relevant improvement from baseline in CAT total score at Year 1 and 2. When assessed by treatment class (or classes), persistence to medication was high (77.8% in Year 1 and 71.4% in Year 2).
Conclusions: Overall, the 2-year follow-up data from DACCORD suggest that for most patients with COPD exacerbations are a rare event. For the majority of patients, the focus should be on managing symptoms, and the impact that these symptoms have on their daily lives. Even for those patients who do exacerbate, although prevention of exacerbations is an important factor, management of symptoms should be a key consideration. DACCORD also suggests that COPD disease progression is not inevitable – providing patients are receiving pharmacological treatment.
This paper aims at reconstructing the development and role of German neurology between 1840 and 1940. Therefore a couple of original sources as well as selected material form the scattered secondary literature were assessed and reviewed. Since the middle of the nineteenth century, an intricate process of separation from internal medicine and psychiatry gradually led to forming a self-conscious community of German neurologists. While Moritz Heinrich Romberg had constructed a cognitive basis for neurology, scientific founders such as Wilhelm Erb, Carl Wernicke, Alois Alzheimer, Hermann Oppenheim, Max Nonne, and many others established the new discipline within modern medicine. In 1891, the first generation of “pure” neurologists succeeded in founding the German Journal for Neurology (Deutsche Zeitschrift für Nervenheilkunde) followed by an autonomous professional organisation, the Society of German Neurologists (Gesellschaft Deutscher Nervenärzte) in 1907. A variety of external factors, however, hampered the institutional evolution and thus the implementation of chairs and departments remained quite modest. In 1935, only 2 years after the National Socialists had seized power, the regulatory merger with the psychiatristsʼ society caused the cautious attempts of German neurologists for autonomy to end in complete failure. The imprisonment, murder and expulsion of neuroscientists declared as Jewish or non-Aryan caused profound changes in neurology, medicine, academic life, and health care in general. Further historical research is needed to reconstruct in detail the involvement of German neurologists in racial-hygienic and eugenic research as well as the institutional and scientific development of German neurology after World War II.
Simple Summary: Cancer immunotherapy mainly targets immune system components, such as immune-suppressive networks generated by cancer cells in the tumor microenvironment (TME). Programmed cell death ligand 1, which is a secretory immune-suppressive factor, is released by tumor-associated macrophages (TAMs). The TME also disrupts production of tumor-specific T cells and generates immunosuppressive leukocytes, regulatory T cells, and myeloid-derived suppressor cells. Immune checkpoint inhibitors are effective in various cancers but only in a subset of patients. Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are dysregulated in cancer through transcriptional, post-transcriptional, and epigenetic changes and have significant roles in cancer initiation and progression, which depends on deregulation of lncRNA expression. TAM function can be influenced by lncRNAs in various ways. However, our understanding of lncRNA dysregulation and function in cancer remains in the early stage.
Abstract: Ever since RNA sequencing of whole genomes and transcriptomes became available, numerous RNA transcripts without having the classic function of encoding proteins have been discovered. Long non-coding RNAs (lncRNAs) with a length greater than 200 nucleotides were considered as “junk” in the beginning, but it has increasingly become clear that lncRNAs have crucial roles in regulating a variety of cellular mechanisms and are often deregulated in several diseases, such as cancer. Lung cancer is the leading cause of cancer-related deaths and has a survival rate of less than 10%. Immune cells infiltrating the tumor microenvironment (TME) have been shown to have a great effect on tumor development with macrophages being the major cell type within the TME. Macrophages can inherit an inflammatory M1 or an anti-inflammatory M2 phenotype. Tumor-associated macrophages, which are predominantly polarized to M2, favor tumor growth, angiogenesis, and metastasis. In this review, we aimed to describe the complex roles and functions of lncRNAs in macrophages and their influence on lung cancer development and progression through the TME.
Background Fermentation of lignocellulosic biomass is an attractive alternative for the production of bioethanol. Traditionally, the yeast Saccharomyces cerevisiae is used in industrial ethanol fermentations. However, S. cerevisiae is naturally not able to ferment the pentose sugars D-xylose and L-arabinose, which are present in high amounts in lignocellulosic raw materials. Results We describe the engineering of laboratory and industrial S. cerevisiae strains to co-ferment the pentose sugars D-xylose and L-arabinose. Introduction of a fungal xylose and a bacterial arabinose pathway resulted in strains able to grow on both pentose sugars. Introduction of a xylose pathway into an arabinose-fermenting laboratory strain resulted in nearly complete conversion of arabinose into arabitol due to the L-arabinose reductase activity of the xylose reductase. The industrial strain displayed lower arabitol yield and increased ethanol yield from xylose and arabinose. Conclusion Our work demonstrates simultaneous co-utilization of xylose and arabinose in recombinant strains of S. cerevisiae. In addition, the co-utilization of arabinose together with xylose significantly reduced formation of the by-product xylitol, which contributed to improved ethanol production.
Formation of pathological anti-FVIII antibodies, or “inhibitors,” is the most serious complication of therapeutic FVIII infusions, affecting up to 1/3 of severe Hemophilia A (HA) patients. Inhibitor formation is a classical T-cell dependent adaptive immune response. As such, it requires help from the innate immune system. However, the roles of innate immune cells and mechanisms of inhibitor development vs. immune tolerance, achieved with or without Immune Tolerance Induction (ITI) therapy, are not well-understood. To address these questions, temporal transcriptomics profiling of FVIII-stimulated peripheral blood mononuclear cells (PBMCs) was carried out for HA subjects with and without a current or historic inhibitor using RNA-Seq. PBMCs were isolated from 40 subjects in the following groups: HA with an inhibitor that resolved either following ITI or spontaneously; HA with a current inhibitor; HA with no inhibitor history and non-HA controls. PBMCs were stimulated with 5 nM FVIII and RNA was isolated 4, 16, 24, and 48 h following stimulation. Time-series differential expression analysis was performed and distinct transcriptional signatures were identified for each group, providing clues as to cellular mechanisms leading to or accompanying their disparate anti-FVIII antibody responses. Subjects with a current inhibitor showed differential expression of 56 genes and a clustering analysis identified three major temporal profiles. Interestingly, gene ontology enrichments featured innate immune modulators, including NLRP3, TLR8, IL32, CLEC10A, and COLEC12. NLRP3 and TLR8 are associated with enhanced secretion of the pro-inflammatory cytokines IL-1β and TNFα, while IL32, which has several isoforms, has been associated with both inflammatory and regulatory immune processes. RNA-Seq results were validated by RT-qPCR, ELISAs, multiplex cytokine analysis, and flow cytometry. The inflammatory status of HA patients suffering from an ongoing inhibitor includes up-regulated innate immune modulators, which may act as ongoing danger signals that influence the responses to, and eventual outcomes of, ITI therapy.
Obesity is associated with an increased risk of heart failure. Little is known about the impact of dietary changes on the cardiac sequelae in obese patients. Twenty-one obese subjects underwent a 12-week low calorie fasting phase of a formula diet. Transthoracic two-dimensional speckle-tracking echocardiography was performed to obtain systolic left ventricular strain before and after weight loss. Body mass index decreased significantly from 38.6 ± 6.2 to 31.5 ± 5.3 kg/m(2), and the total percentage fat loss was 19%. Weight reduction was associated with a reduction in blood pressure and heart rate. Left ventricular longitudinal global peak systolic strain was in the lower normal range (-18.7 ± 3.2%) before weight loss and was unchanged (-18.8 ± 2.4%) after 12 weeks on diet with substantial weight loss. Also, no significant change in global radial strain after weight loss was noted (41.1 ± 22.0 versus 43.9 ± 23.3, p = 0.09). Left atrial and ventricular dimensions were in normal range before fasting and remained unchanged after weight loss. In our study obesity was associated with normal systolic left ventricular function. A 12-week low calorie diet with successful weight loss can reduce blood pressure and heart rate. Systolic left ventricular function and morphology were not affected by rapid weight reduction.
Background/objectives: Obesity is independently associated with left ventricular (LV) diastolic dysfunction and altered cardiac morphology. Morbidity and mortality in patients with diastolic dysfunction are similar to values observed in patients with systolic heart failure. We hypothesized that dysfunctional cardiac responses in people with obesity are reversible after weight loss. Thus, we studied the effect of dietary weight reduction on LV diastolic function as well as on cardiac structure using transthoracic echocardiography and tissue Doppler imaging (TDI).
Subjects/methods: Thirty-two subjects with obesity underwent a 12-week low-calorie fasting phase of a formula diet. Echocardiographic tissue Doppler indices of diastolic function and measurements of cardiac size were obtained prior to and after the fasting phase.
Results: A 12-week diet significantly reduced body mass index from 40.3 ± 6.6 kg/m 2 to 33.2 ± 6.1 kg/m 2 ( p < 0.01). Weight loss was associated with a significant reduction in blood pressure and heart rate. Echocardiography revealed diastolic dysfunction in subjects with obesity, which was improved by dieting. After weight loss, trans-mitral Doppler echocardiography showed a significant reduction in A-wave velocity, from 65.8 ± 19.2 cm/s to 57.0 ± 16.8 cm/s, and an increase in E/A ratio from 1.2 ± 0.4 to 1.4 ± 0.5 ( p < 0.01). TDI displayed a significantly lower a'-wave velocity (10.3 ± 2.3 cm/s and 8.9 ± 1.7 cm/s; p < 0.01). Left atrial and LV dimensions were normal and remained unchanged after weight loss.
Conclusion: Obesity is associated with diastolic dysfunction. A 12-week low-calorie diet with successful weight loss can reduce blood pressure and heart rate and partially normalize diastolic dysfunction.
Site-specific recombinases (SSR) are utilized as important genome engineering tools to precisely modify the genome of mice and other model organisms. Reporter mice that mark cells that at any given time had expressed the enzyme are frequently used for lineage tracing and to characterize newly generated mice expressing a recombinase from a chosen promoter. With increasing sophistication of genome alteration strategies, the demand for novel SSR systems that efficiently and specifically recombine their targets is rising and several SSR-systems are now used in combination to address complex biological questions in vivo. Generation of reporter mice for each one of these recombinases is cumbersome and increases the number of mouse lines that need to be maintained in animal facilities. Here we present a multi-reporter mouse line for loci-of-recombination (X) (MuX) that streamlines the characterization of mice expressing prominent recombinases. MuX mice constitutively express nuclear green fluorescent protein after recombination by either Cre, Flp, Dre or Vika recombinase, rationalizing the number of animal lines that need to be maintained. We also pioneer the use of the Vika/vox system in mice, illustrating its high efficacy and specificity, thereby facilitating future designs of sophisticated recombinase-based in vivo genome engineering strategies.
Wickler der Sandtrockenrasen bei Halle (Saale)-Nietleben und ihre Bedeutung für den Naturschutz
(1993)
In den Jahren 1988 bis 1992 wurden die nordöstlich des Heidesees bei Halle (Saale)-Nietleben gelegenen Streuobstwiesen, die als geschützter Landschaftsbestandteil nach NatSchG LSA einstweilig gesichert sind, ziemlich eingehenden kleinschmetterlingskundlichen Erhebungen unterzogen. Die Untersuchungen erfolgten mit freundlicher Genehmigung der zuständigen Behörden. Der Schwerpunkt lag in der Ermittlung derjenigen Schmetterlingsarten, die als typisch für die die Streuobstwiesen kennzeichnenden Sandtrockenrasen anzusehen sind. Um eine leichtere Zuordnung der aufgefundenen Arten zu ermöglichen, wurden insbesondere Tagesexkursionen in das Gebiet durchgeführt. Von den beobachteten Arten wurden Belege eingesammelt bzw. die Spezies, die im Freiland sicher bestimmbar waren, an Ort und Stelle notiert. Die nachfolgende Auswertung berücksichtigt neben den Daten des Autors auch die Aufsammlungen von Herrn T. Süssmuth, Radeberg, aus dem gleichen Zeitraum.
Südlich von Wurzen verlässt die Vereinigte Mulde das Sächsische Hügelland und strömt in einer flachen, meist drei bis vier Kilometer breiten Talwanne nach Norden, oftmals eingerahmt von Talsandterrassen. Oberhalb von Dessau weitet sich das Muldetal in Richtung Osten und vereinigt sich mit der Elbeaue. Nördlich von Dessau mündet die Mulde in die Elbe. Für die zwischen den Deichen gelegenen Auenabschnitte an der Mulde war eine Wiesen- und Weidenutzung sehr charakteristisch. Überflutungen des Auengrünlandes zwischen den Deichen kommen regelmäßig vor, wobei erwartungsgemäß die grundwassernahen Flächen deutlich häufiger betroffen sind als die grundwasserfernen. Werden Letztere überstaut, so ist die gesamte Überflutungsaue wassergefüllt. Kleine, wenig bewegungsaktive Tierarten haben kaum Rückzugsmöglichkeiten und viele ertrinken im Wasser. Dies gilt z. B. für Schmetterlingsraupen und bei längerer Dauer der Überstauung auch für Eier, Puppen und Falter. Darum erschien es sehr interessant, die Folgen der ausgedehnten und hohen Überflutung der Muldeaue im August 2002 am Beispiel der Schmetterlingsfauna eines Sandtrockenrasens in der Aue östlich von Dessau zu studieren.
In der kurzen Abhandlung über geschützte und gefährdete Pflanzen, Tiere und Landschaften des Landes Sachsen-Anhalt wird auf Arten der Kalttrocken- sowie Magerrasen eingegangen. Beschrieben werden der weiße Dost- oder Schmuck-Kleinspanner (Scopula ornata) dessen Flügelspanne nur etwa zwei Zentimeter misst und der zu den Spannerfaltern (Geometridae) zählt, sowie der kastanienbraune Schmalflügelzünsler (Selagia spadicella), der innerhalb der Zünslerfalter (Pyralidae) zur Unterfamilie Phycitinae gehört. Als Pflanze des Magerrasens wird die Herbstwendelorchis (Spiranthes spiralis) als eine stark gefährdete Orchideenart aufgeführt.
Background: The Global Burden of Diseases Study 2017 predicted that chronic obstructive pulmonary disease (COPD) is the second leading cause of death, the fourth leading cause of premature death, and the third cause for DALYs lost in Nepal. However, data on the population-based prevalence of COPD in Nepal are very limited. This study aims to assess the prevalence of COPD and factors associated with the occurrence of COPD in Nepal.
Methods: From a nationally representative, population-based cross-sectional study on chronic non-communicable diseases, the prevalence of COPD and its associated factors was determined. Of 12,557 participants aged over 20 years, 8945 participants completed a questionnaire and spirometry. Eligible participants were also asked to answer a COPD diagnostic questionnaire for screening COPD cases, and if needed underwent pre-bronchodilator and post-bronchodilator spirometry. COPD was defined as a post-bronchodilator FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio of < 0.70. Multivariate logistic regression was performed to identify factors associated with COPD. Sampling weights were used for all data analyses.
Results: The prevalence of COPD in Nepal was 11.7% (95% CI: 10.5% to 12.9 %), which increased with age, and higher in those with a low educational level, those who had smoked ≥ 50 pack-years, persons having a low body mass index (BMI), and residents of Karnali province. Multivariate analysis revealed that being aged 60 years and above, having a low BMI, low educational status, having smoked more than 50 pack-years, provincial distribution, and ethnicity were independent predictors of COPD.
Conclusion: COPD is a growing and serious public health issue in Nepal. Factor such as old age, cigarette smoking, low educational attainment, low BMI, ethnicity, and locality of residence (province-level variation) plays a vital role in the occurrence of COPD. Strategies aimed at targeting these risk factors through health promotion and education interventions are needed to decrease the burden of COPD.
Prähistorische Eierschalenfragmente der Fundstelle Sulze bei Erfurt in Thüringen werden beschrieben und diskutiert. Die folgenden Arten werden nachgewiesen: Cygnus olor, Anser anser, Anas platyrhynchos und Gallus gallus forma domestica. Auf der Grundlage von Knochenresten gelten folgende Nachweise: Columba livia forma domestica, Tyto alba, Anser anser forma domestica, Anas platyrhynchos forma domestica, Gallus gallus forma domestica, Corvus corax, Coloelus monedula, Galerida cristata, Passer domesticus und Coccothraustes coccothraustes. Besonderes Gewicht wird auf die Bestimmungsmethoden an prähistorischen Eierschalen gelegt.
Meeting Abstract : Deutsche Gesellschaft für Chirurgie. 125. Kongress der Deutschen Gesellschaft für Chirurgie. Berlin, 22.-25.04.2008 Einleitung: Über 4 Millionen Menschen leben in Deutschland schätzungsweise mit chronischen Wunden. Aufgrund der demographischen Entwicklung unserer Gesellschaft ist mit einem weiteren Anstieg der zu nicht, oder nur zögerlich heilenden Wunden führenden Erkrankungen diabetisches Fußsyndrom, chronisch venöse Insuffizienz und pAVK auszugehen. Dennoch ist die moderne hydroaktive Wundbehandlung in Deutschland nicht flächendeckend etabliert. Gründe hierfür liegen unter anderem in dem unüberschaubaren Produktsortiment, der unzureichenden Vergütung vor allem im ambulanten Versorgungssektor und in der mangelhaften ärztlichen Ausbildung in Bezug auf Wundtherapie. Ein standardisiertes Wundbehandlungsschema erleichtert die stadiengerechte Anwendung moderner Wundauflagen und dient als nachvollziehbare Entscheidungsgrundlage in der Auswahl der erforderlichen Wundprodukte. Material und Methoden: Anhand eines Bogens werden vier Kriterien (Wundstadium, Wundexsudation, Wundtiefe und Wundinfektion) zur Beurteilung einer Wunde erfasst. Die fotographische Abbildung der verschiedenen Wundstadien erlaubt eine sichere visuelle Zuordnung durch den Therapeuten. Nach Analyse dieser S.E.T.I. Kriterien ergibt sich eine eindeutige stadiengerechte Produktzuordnung, die auch dem weniger geübten eine sichere Anwendung der verschiedenen Produktgruppen ermöglicht. Ergebnisse: Dieser Behandlungsstandard wurde zwischenzeitlich an 3 Kliniken der Maximalversorgung und in einem integrierten Versorgungsmodell zum diabetischen Fußsyndrom etabliert und stellt einen Bestandteil für ein weiteres IV Modell zur pAVK dar. Neben ökonomischen Vorteilen (reduzierte Lagerhaltungskosten, Straffung des Produktsortiments, günstigere Bezugskonditionen) lässt sich eine Verbesserung in der Behandlungsqualität, eine verkürzte stationäre Behandlungsdauer sowie eine vereinfachte Umsetzung einer sektorenübergreifenden Wundversorgung erzielen. Schlussfolgerung: Die Anwendung eines Therapiestandards für die stadiengerechte Behandlung chronischer Wunden ermöglicht eine Anwenderunabhängige gleich bleibend hohe Qualität sowie eine wesentlich vereinfachte Orientierung in dem Produktsortiment. Hierdurch wird weiterhin ein Beitrag zur Schnittstellenoptimierung zwischen dem stationären und ambulanten Versorgungssektor bei chronischen Wunden geleistet. Ein verbindlicher interdisziplinärer und interprofessioneller Wundbehandlungsstandard stellt eine unverzichtbare Qualitätssicherungsmaßnahme in der Wundbehandlung dar.
Rad se bavi analizom svojstava, funkcija i markera konverzacijkih implikatura u SMS diskursu. U prvome dijelu članka utvrđuju se temeljni mehanizmi prijenosa implicitnih intencionalno enodiranih sadržaja u diskurs te se određuju obilježja jezične strukture i govorne produkcije tipična za dopisivanje putem SMS poruka. Diskurs SMS dopisivanja smatra se plodnim područjem za proučavanje implikatura zbog bogatstva implicitnim sadržajima (uvjetovanoga sažetošću SMS forme); posrednosti komunikacije koja iziskuje jezično ili znakovno markiranje implikatura te specifičnih načina prijenosa i signaliziranja implicitnih sadržaja. U drugome dijelu rada predstavljaju se paralingvistički i jezični markeri konverzacijskih implikatura koji su se temeljem analize korpusa SMS dopisivanja pokazali najzastupljenijima u upotrebi. Cilj je rada ukazati na specifičnosti SMS diskursa kada su u pitanju sredstva i mehanizmi enkodiranja, signaliziranja te uspješnoga dekodiranja implicitnih sadržaja.
Surviving death: emerging concepts of RIPK3 and MLKL ubiquitination in the regulation of necroptosis
(2021)
Lytic forms of programmed cell death, like necroptosis, are characterised by cell rupture and the release of cellular contents, often provoking inflammatory responses. In the recent years, necroptosis has been shown to play important roles in human diseases like cancer, infections and ischaemia/reperfusion injury. Coordinated interactions between RIPK1, RIPK3 and MLKL lead to the formation of a dedicated death complex called the necrosome that triggers MLKL-mediated membrane rupture and necroptotic cell death. Necroptotic cell death is tightly controlled by post-translational modifications, among which especially phosphorylation has been characterised in great detail. Although selective ubiquitination is relatively well-explored in the early initiation stages of necroptosis, the mechanisms and functional consequences of RIPK3 and MLKL ubiquitination for necrosome function and necroptosis are only starting to emerge. This review provides an overview on how site-specific ubiquitination of RIPK3 and MLKL regulates, fine-tunes and reverses the execution of necroptotic cell death.
Unmotivated and unprepared, an Austrian young man leaves his home town Vienna, only to dive into the unknown Romania. He already has images of this country in his mind. He is on his way towards the magical, dark, sparkling Transdanubien, about which he only knows clichés: that Romanians barely have anything to eat, that it is a country of gypsies, that the official language is Russian, that it is an anachronistic country par excellence. With this perspective, his relationship with local Ilina can only fail. This article follows along the lines of a complicated inter-cultural communication.
Looking back, my memories seem like distant, made-up stories. These words of the main character are to be found all over Jan Koneffkes novel. A foreigner on the run, Felix Kannmacher is forced to tell stories in order to survive. He is at the mercy of a teenager who is avid for constantly new and different bedtime stories. Felix gives in, as he has no other choice but to be a slaveto this child. The following article analyses the fine line between the stories Felix invents for Virginia and two narratological aspects: the actual plot of the novel on the one hand, and the actual course of history, on the other. The entire novel is built on stories-within-stories that twist and turn the course of Story and History alike. Because each one of us writes their own (hi)story.
For intercultural language teaching, coaching students on how to perceive the cultural “other” is of crucial importance in order to avoid culturally based misunderstandings. This paper explores how perceiving the other can offer conclusions for perceiving and becoming aware of the self. Through that, a process of giving and taking ensues in which perceptions of the self and of the other are constantly fluctuating depending on the context in which the communication is taking place. At the crossroads between members of two different cultures, a dialogue emerges in which the points of view of both parties are changed. The paper outlines how perception is a construct in which one’s own origin, education, and emotions are blended in. Intercultural learning is the way to deal with this constructs in a flexible manner so as to create new interpretation patterns. It teaches how to sympathize with the other and how to better understand oneself.
Film is a wonderful means of reflecting upon the identity of the self and the other. A movie like Didi Danquart’s Offset (2006), which deals with intercultural conflicts, even more so. The clash of the Romanian and German cultures depicted in this movie illustrates how the construction of identity – of the self and the other – works.
Using literature in culture and civilization classes enables the contact to foreign culture. Literature does not merely copy reality, but has its own rules of story telling, its own way of changing the perspective on reality, of correcting cliches, in omitting something, so as for the reader to become curious and fill in these „gaps”. In this paper, a fragment from a novel shows how a german businessman arriving in interbellic Romania finds that time is measured differently in those two countries.
Prämissen für die Vermittlung interkultureller Kompetenzen im studienbegleitenden DaF-Unterricht
(2014)
Language teaching alone is not sufficient in order to communicate successfully in the foreign language. Even with the acquisition of one’s native language, one does not learn just vocabulary, grammar, reading, writing, speaking and listening. Apart from all that one learns how to identify and to practice cultural patterns. Here, the learning and teaching process is accompanied by another component: intercultural communication and the acquisition of intercultural competences. These teach the lerner to understand first and foremost their own cultural background in order for them to be able to change perspective and look at and understand the cultural background of the target language. Teaching must be centered on the learner, and the foreign language is not taught „in general“, but with regard to the learners’ culture of origin.
Language teaching through the medium of film may prove very rewarding in that it moves the focus away from language and its general markers (grammar, vocabulary) alone and casts it onto culture, cultural boundaries and rules. Among them, space plays a very important role. It defines who we are, where we come from. Especially the fine line between what is considered public or private space is worth being analyzed. With examples from two movies, students of German as a Foreign Language are meant to discover this fine line, look beyond it and restore an equilibrium between the public and the private in order to be prepared for intercultural experiences.
Cosmin, a twelve-year-old Roma boy from Transylvania, only goes to school for a short while. For his mother, it is more important, that he, the only male of a household with many mouths to feed, help her with work. But Cosmin’s teacher does not give up and proposes a bargain: If Cosmin’s mother lets her children go to school, she will get electricity from the school to be able to watch TV. Due to this arrangement, Cosmin returns to school for a few days, becomes a little thief and embarks on a journey that can become an opportunity for him. A kind of a bildungsroman, a coming of age novel focused on the ups and downs between two worlds on Romanian soil, that could not be more different from one another: the Romanian majority and the Roma minority. This article sets out to document life at the brink of society, with all of its facets.
Background: Current prognostic gene signatures for breast cancer mainly reflect proliferation status and have limited value in triple-negative (TNBC) cancers. The identification of prognostic signatures from TNBC cohorts was limited in the past due to small sample sizes.
Methodology/Principal Findings: We assembled all currently publically available TNBC gene expression datasets generated on Affymetrix gene chips. Inter-laboratory variation was minimized by filtering methods for both samples and genes. Supervised analysis was performed to identify prognostic signatures from 394 cases which were subsequently tested on an independent validation cohort (n = 261 cases).
Conclusions/Significance: Using two distinct false discovery rate thresholds, 25% and <3.5%, a larger (n = 264 probesets) and a smaller (n = 26 probesets) prognostic gene sets were identified and used as prognostic predictors. Most of these genes were positively associated with poor prognosis and correlated to metagenes for inflammation and angiogenesis. No correlation to other previously published prognostic signatures (recurrence score, genomic grade index, 70-gene signature, wound response signature, 7-gene immune response module, stroma derived prognostic predictor, and a medullary like signature) was observed. In multivariate analyses in the validation cohort the two signatures showed hazard ratios of 4.03 (95% confidence interval [CI] 1.71–9.48; P = 0.001) and 4.08 (95% CI 1.79–9.28; P = 0.001), respectively. The 10-year event-free survival was 70% for the good risk and 20% for the high risk group. The 26-gene signatures had modest predictive value (AUC = 0.588) to predict response to neoadjuvant chemotherapy, however, the combination of a B-cell metagene with the prognostic signatures increased its response predictive value. We identified a 264-gene prognostic signature for TNBC which is unrelated to previously known prognostic signatures.