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The deregulation of Polo-like kinase 1 is inversely linked to the prognosis of patients with diverse human tumors. Targeting Polo-like kinase 1 has been widely considered as one of the most promising strategies for molecular anticancer therapy. While the preclinical results are encouraging, the clinical outcomes are rather less inspiring by showing limited anticancer activity. It is thus of importance to identify molecules and mechanisms responsible for the sensitivity of Polo-like kinase 1 inhibition. We have recently shown that p21Cip1/CDKN1A is involved in the regulation of mitosis and its loss prolongs the mitotic duration accompanied by defects in chromosome segregation and cytokinesis in various tumor cells. In the present study, we demonstrate that p21 affects the efficacy of Polo-like kinase 1 inhibitors, especially Poloxin, a specific inhibitor of the unique Polo-box domain. Intriguingly, upon treatment with Polo-like kinase 1 inhibitors, p21 is increased in the cytoplasm, associated with anti-apoptosis, DNA repair and cell survival. By contrast, deficiency of p21 renders tumor cells more susceptible to Polo-like kinase 1 inhibition by showing a pronounced mitotic arrest, DNA damage and apoptosis. Furthermore, long-term treatment with Plk1 inhibitors induced fiercely the senescent state of tumor cells with functional p21. We suggest that the p21 status may be a useful biomarker for predicting the efficacy of Plk1 inhibition.
The transcription factor Tal1 is a critical activator or repressor of gene expression in hematopoiesis and leukaemia. The mechanism by which Tal1 differentially influences transcription of distinct genes is not fully understood. Here we show that Tal1 interacts with the peptidylarginine deiminase IV (PADI4). We demonstrate that PADI4 can act as an epigenetic coactivator through influencing H3R2me2a. At the Tal1/PADI4 target gene IL6ST the repressive H3R2me2a mark triggered by PRMT6 is counteracted by PADI4, which augments the active H3K4me3 mark and thus increases IL6ST expression. In contrast, at the CTCF promoter PADI4 acts as a repressor. We propose that the influence of PADI4 on IL6ST transcription plays a role in the control of IL6ST expression during lineage differentiation of hematopoietic stem/progenitor cells. These results open the possibility to pharmacologically influence Tal1 in leukaemia.
Predominant polarity in bipolar disorder and validation of the polarity index in a German sample
(2014)
Background: A large number of patients with bipolar disorder (BD) can be characterized by predominant polarity (PP), which has important implications for relapse prevention. Recently, Popovic et al. (EUR NEUROPSYCHOPHARM 22(5): 339¿346, 2012) proposed the Polarity Index (PI) as a helpful tool in the maintenance treatment of BD. As a numeric expression, it reflects the efficacy of drugs used in treatment of BD. In the present retrospective study, we aimed to validate this Index in a large and well characterized German bipolar sample.
Methods: We investigated 336 bipolar patients (BP) according to their PP and calculated the PI for each patient in order to prove if maintenance treatment differs according to their PP. Furthermore, we analysed whether PP is associated with demographic and clinical characteristics of BP.
Results: In our sample, 63.9% of patients fulfilled criteria of PP: 169 patients were classified as depressive predominant polarity (DPP), 46 patients as manic predominant polarity (MPP). The two groups differed significantly in their drug regime: Patients with DPP were more often medicated with lamotrigine and antidepressants, patients with MPP were more often treated with lithium, valproate, carbamazepine and first generation antipsychotics. However, patients with DPP and MPP did not differ significantly with respect to the PI, although they received evidence-based and guideline-driven treatment.
Conclusion: The reason for this negative finding might well be that for several drugs, which were used frequently, no PI value is available. Nevertheless we suggest PP as an important concept in the planning of BD maintenance treatment.
Background: In this study, we examined patients who had non-progressive disease for at least 2 years after diagnosis of inoperable locoregional recurrent or metastatic breast cancer under continuous trastuzumab treatment. Our primary goal was to assess the long-term outcome of patients with durable response to trastuzumab.
Methods: 268 patients with HER2-positive inoperable locally recurrent or metastatic breast cancer and non-progressive disease for at least 2 years under trastuzumab treatment were documented retrospectively or prospectively in the HER-OS registry, an online documentation tool, between December 2006 and September 2010 by 71 German oncology centers. The study end point was time to tumor progression.
Results: Overall, 47.1% of patients (95% confidence interval (CI): 39.9–54.1%) remained in remission for more than 5 years, while the median time to progression was 4.5 years (95% CI: 4.0–6.6 years). Lower age (<50 years) and good performance status (ECOG 0) at time of trastuzumab treatment initiation as well as complete remission after initial trastuzumab treatment were associated with longer time to progression. Interruption of trastuzumab therapy correlated with shorter time to progression.
Conclusions: HER2-positive patients, who initially respond to palliative treatment with trastuzumab, can achieve a long-term tumor remission of several years.
Zur Flora von Deutschland gehören sieben Arten der Wintergrüngewächse, die alle auch in Sachsen-Anhalt heimisch sind: Dolden-Winterlieb (Chimaphila umbellata [L.] BARTON), Einblütiges Wintergrün (Moneses uniflora [L.] A. GRAY), Birngrün (Orthilia secunda [L.] HOUSE), Grünblütiges Wintergrün (Pyrola chlorantha SW.), Mittleres Wintergrün (Pyrola media SW.), Kleines Wintergrün (Pyrola minor L.) und Rundblättriges Wintergrün (Pyrola rotundifolia L.). Im Mittelpunkt dieses Beitrages steht nur die aktuelle Verbreitung im Bundesland mit Bezug auf MTB-Q4, und zwar bezogen auf zwei Perioden von jeweils 10 Jahren: Nachweise im MTB-Q4 von 2005 bis 2014, sowie Nachweise im MTB-Q4 von 1995 bis 2004.
Die Mauerkronen der Nicolai-Kirche in Zerbst wurden im Jahr 2001 mit unterschiedlichen Methoden begrünt. Das Ziel dieser Maßnahmen war die Pufferung extremer Temperaturunterschiede, die häufig zu starken Schäden am Mauerwerk führen. In Vorbereitung von anstehenden Sanierungsmaßnahmen wurde der Artenbestand auf repräsentativen Abschnitten der Mauern erfasst. Auf diese Weise konnte ermittelt werden, welche Arten mit den extremen Standortbedingungen, wie Hitze, Trockenheit und große Temperaturunterschiede gut zurechtkommen und daher bei der Sanierung an Fehlstellen erfolgversprechend angesiedelt werden können.
Das Vorkommen von Bunias orientalis (Orientalische Zackenschote) konzentriert sich auf den Südwesten Sachsen-Anhalts. Bisher ist die Art vorrangig aus dem Straßenbegleitgrün bekannt, doch zunehmend kann das Einwandern in Halbtrockenrasen und Frischwiesen beobachtet werden. Ein Beispiel dafür ist die 2011 eingerichtete und ca. 24 ha große Ganzjahresstandweide bei Hainrode. 2013 konnten hier 58 Fundpunkte mit 644 Sprossen dokumentiert werden. Die Art wird von den weidenden Salers angenommen und verbissen. Das Abfressen führt zu geringeren Wuchshöhen und vermutlich ist die Reproduktion über Samen auch bei Neuaustrieb deutlich herabgesetzt. Es wird die Möglichkeit, mittels Beweidung der Südharzer Frischwiesen die weitere Ausbreitung von Bunias orientalis zu verhindern bzw. die Art über eine Beweidung zurückzudrängen, diskutiert.
Oscillations play a critical role in cognitive phenomena and have been observed in many brain regions. Experimental evidence indicates that classes of neurons exhibit properties that could promote oscillations, such as subthreshold resonance and electrical gap junctions. Typically, these two properties are studied separately but it is not clear which is the dominant determinant of global network rhythms. Our aim is to provide an analytical understanding of how these two effects destabilize the fluctuation-driven state, in which neurons fire irregularly, and lead to an emergence of global synchronous oscillations. Here we show how the oscillation frequency is shaped by single neuron resonance, electrical and chemical synapses.The presence of both gap junctions and subthreshold resonance are necessary for the emergence of oscillations. Our results are in agreement with several experimental observations such as network responses to oscillatory inputs and offer a much-needed conceptual link connecting a collection of disparate effects observed in networks.
A measurement of the transverse momentum spectra of jets in Pb-Pb collisions at sNN−−−√=2.76 TeV is reported. Jets are reconstructed from charged particles using the anti-kT jet algorithm with jet resolution parameters R of 0.2 and 0.3 in pseudo-rapidity |η|<0.5. The transverse momentum pT of charged particles is measured down to 0.15 GeV/c which gives access to the low pT fragments of the jet. Jets found in heavy-ion collisions are corrected event-by-event for average background density and on an inclusive basis (via unfolding) for residual background fluctuations and detector effects. A strong suppression of jet production in central events with respect to peripheral events is observed. The suppression is found to be similar to the suppression of charged hadrons, which suggests that substantial energy is radiated at angles larger than the jet resolution parameter R=0.3 considered in the analysis. The fragmentation bias introduced by selecting jets with a high pT leading particle, which rejects jets with a soft fragmentation pattern, has a similar effect on the jet yield for central and peripheral events. The ratio of jet spectra with R=0.2 and R=0.3 is found to be similar in Pb-Pb and simulated PYTHIA pp events, indicating no strong broadening of the radial jet structure in the reconstructed jets with R<0.3.
This study investigates the diabetes-associated alterations present in cardiac mesenchymal cells (CMSC) obtained from normoglycemic (ND-CMSC) and type 2 diabetic patients (D-CMSC), identifying the histone acetylase (HAT) activator pentadecylidenemalonate 1b (SPV106) as a potential pharmacological intervention to restore cellular function. D-CMSC were characterized by a reduced proliferation rate, diminished phosphorylation at histone H3 serine 10 (H3S10P), decreased differentiation potential, and premature cellular senescence. A global histone code profiling of D-CMSC revealed that acetylation on histone H3 lysine 9 (H3K9Ac) and lysine 14 (H3K14Ac) was decreased, whereas the trimethylation of H3K9Ac and lysine 27 significantly increased. These observations were paralleled by a downregulation of the GCN5-related N-acetyltransferases (GNAT) p300/CBP-associated factor and its isoform 5-α general control of amino acid synthesis (GCN5a), determining a relative decrease in total HAT activity. DNA CpG island hypermethylation was detected at promoters of genes involved in cell growth control and genomic stability. Remarkably, treatment with the GNAT proactivator SPV106 restored normal levels of H3K9Ac and H3K14Ac, reduced DNA CpG hypermethylation, and recovered D-CMSC proliferation and differentiation. These results suggest that epigenetic interventions may reverse alterations in human CMSC obtained from diabetic patients.
Cytokine-regulated GADD45G induces differentiation and lineage selection in hematopoietic stem cells
(2014)
The balance of self-renewal and differentiation in long-term repopulating hematopoietic stem cells (LT-HSC) must be strictly controlled to maintain blood homeostasis and to prevent leukemogenesis. Hematopoietic cytokines can induce differentiation in LT-HSCs; however, the molecular mechanism orchestrating this delicate balance requires further elucidation. We identified the tumor suppressor GADD45G as an instructor of LT-HSC differentiation under the control of differentiation-promoting cytokine receptor signaling. GADD45G immediately induces and accelerates differentiation in LT-HSCs and overrides the self-renewal program by specifically activating MAP3K4-mediated MAPK p38. Conversely, the absence of GADD45G enhances the self-renewal potential of LT-HSCs. Videomicroscopy-based tracking of single LT-HSCs revealed that, once GADD45G is expressed, the development of LT-HSCs into lineage-committed progeny occurred within 36 hr and uncovered a selective lineage choice with a severe reduction in megakaryocytic-erythroid cells. Here, we report an unrecognized role of GADD45G as a central molecular linker of extrinsic cytokine differentiation and lineage choice control in hematopoiesis.
Use of drug-eluting balloon coronary intervention prior to living donor kidney transplantation
(2014)
Background: Kidney transplantation is the gold standard of therapy in patients with terminal renal insufficiency. Living donor transplantation is a well-established option in this field. Enlarging the donor's pool implicates the acceptance of an increased rate of comorbidities. Among them, coronary artery disease is a growing problem. An increasing number of patients, undergoing living donation, receive antiplatelet therapies due to coronary disease.
Case presentation: Here we report about the perioperative treatment with a drug-eluting balloon in a patient with major cardiac risk factors who underwent kidney transplantation.
Conclusion: At the current time no recommendation can be given for the routine use of drug-eluting balloons.
Linear Ubiquitin chain Assembly Complex (LUBAC) is an E3 ligase complex that generates linear ubiquitin chains and is important for tumour necrosis factor (TNF) signaling activation. Mice lacking Sharpin, a critical subunit of LUBAC, spontaneously develop inflammatory lesions in the skin and other organs. Here we show that TNF receptor 1 (TNFR1)-associated death domain (TRADD)-dependent TNFR1 signaling in epidermal keratinocytes drives skin inflammation in Sharpin-deficient mice. Epidermis-restricted ablation of Fas-associated protein with death domain (FADD) combined with receptor-interacting protein kinase 3 (RIPK3) deficiency fully prevented skin inflammation, while single RIPK3 deficiency only delayed and partly ameliorated lesion development in Sharpin-deficient mice, showing that inflammation is primarily driven by TRADD- and FADD-dependent keratinocyte apoptosis while necroptosis plays a minor role. At the cellular level, Sharpin deficiency sensitized primary murine keratinocytes, human keratinocytes, and mouse embryonic fibroblasts to TNF-induced apoptosis. Depletion of FADD or TRADD in Sharpin-deficient HaCaT cells suppressed TNF-induced apoptosis, indicating the importance of FADD and TRADD in Sharpin-dependent anti-apoptosis signaling in keratinocytes.
Ziel: Die Evaluation der DEGUM-Mammasonografiekurse nach objektivierbaren Kriterien war Ziel dieser Arbeit. Damit sollte die Qualität der Kurse überprüft werden, um eine flächendeckende Fort- und Weiterbildung auf hohem Niveau anzubieten.
Material und Methoden: 10 Qualitätskriterien, orientierend an den Vorgaben der KBV-Ultraschallvereinbarungen wurden als Qualitätsparameter definiert. Alle Kursleiter des Arbeitskreises Mammasonografie der DEGUM wurden angeschrieben. Dabei wurden die 10 definierten Qualitätskriterien überprüft.
Ergebnisse: Alle Kurse erfüllten die Voraussetzungen bezüglich der Qualität des Kursleiters, der Kursdauer und Unterrichtseinheiten sowie der Anzahl an Kursteilnehmern pro Ultraschallgerät. In 1 von 9 Kursen wurde die Zeit der praktischen Übungen, gefordert sind 50 %, unterschritten. Die Voraussetzungen für den Abschlusskurs (200 selbst durchgeführte und dokumentierte Fälle) sind in den Kursankündigungen zum Teil nicht klar definiert. Ein strukturierter Lehrkatalog fehlt.
Schlussfolgerung: Die DEGUM-Mammasonografiekurse werden auf hohem Niveau angeboten und erfüllen zum größten Teil die Anforderungen der KBV. Trotz der hohen Qualität der DEGUM-Kurse sind Optimierungsoptionen im Bereich Kursankündigung und strukturierter Lehrkatalog möglich.
Dil öğretiminde geleneksel öğretmen merkezli ve dilbilgisi ağırlıklı metotlardan gitgide uzaklaşılmaktadır. Bu çalışmada işitsel ve görsel araçlardan biri olarak tiyatronun ders dışı sosyal aktivite olarak kullanımı ve öğrenimi hızlandırıcı etkisi incelenmiştir.
Bu amaç ile Akdeniz Üniversitesi Yabancı Diller Yüksekokulu tarafından Türkiye Burslusu 43 farklı ülkeden 70 öğrenciye (Tablo1) 30 Eylül 2013-27 Haziran 2014 tarihleri arasında verilen Türkçe eğitimi programı kullanılmıştır. Öğrencilere 960 saat Türkçe eğitimi verilmesinin yanı sıra haftada 2 saatten az olmamak üzere sosyal aktivite adı altında ek çalışmalara (koro, dans, tiyatro vs.) yönlendirilmişlerdir.
Bu çalışmada, hedef dilin öğretilmesinde tiyatro tekniğinin/ çalışmalarının öğrencinin hedef dildeki performansına etkisini belirlemek amacıyla ön test-son test kontrol gruplu yarı deneysel araştırma deseni kullanılmıştır.
Çalışma sonunda; Konuşma becerisi açısından bakıldığında Yabancı Dil Olarak Türkçe'nin Öğretilmesi (YDT) konusunda Akdeniz Üniversitesi Yabancı Diller Yüksekokulu bünyesinde ders dışında ‒ sosyal etkinlik olarak ‒ uygulanmakta olan Tiyatro Çalışmalarının öğrencilerin dil edinme performanslarına etkisinin olumlu olduğu bulgusuna ulaşılmıştır. Bununla beraber, üç alt bulgu da tespit edilmiştir: Konuşma becerisi açısından bakıldığında tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılığın olduğu sınav sonuçlarının analizi ile ortaya konulmuştur. Ayrıca, Yeterlik sınav sonucu değerlendirildiğinde tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılığın da tespiti yapılmıştır. Bunlara ek olarak, "Motivasyon açısından bakıldığında, tiyatro çalışmalarını takip eden öğrenciler ile bu çalışmalara katılmayan öğrencilerin sınav sonuçları arasında belirli bir farklılık var mıdır?" alt hipotezi de tiyatro çalışmalarının öğrenci motivasyonunu arttırdığı belirlenmiştir.
Bu bağlamda, her hafta hazırlanan öğrenci gelişim raporu ile öğrencinin dil gelişimi, motivasyonu ve öğrencinin ilgi alanları (müzik, dans, drama vs.) danışman öğretim elemanları tarafından değerlendirilmesi uygulamalarına gelecek akademik yıllarda da devam edilmesi kurumca kararlaştırılmıştır.
2013 yılında ilk kez gerçekleştirilen Öğretmenler için Alan Bilgisi (ÖABT) Almanca sınavı üniversitelerin Alman Dili Eğitimi Anabilim Dallarında ve Alman Dili ve Edebiyatı Bölümlerinde okuyan lisans öğrencileri için umut kapısı olmuştur. Bu bölümlerin öğrencileri önceki yıllarda "mezun olup diploma sahibi olmak" gibi bir amaçla okuduklarından dolayı derslere karşı motivasyonları düşük kalmaktaydı. ÖABT ve beraberinde getirdiği Almanca öğretmeni olarak atanma fırsatı sayesinde bu öğrenciler artık lisans eğitimlerini daha fazla ciddiye almaya ve olabildiğince donanımlı bir şekilde mezun olmaya çalışmaktadır.
Yukarıdaki bilgilerden hareketle bu çalışmamızda öncelikli olarak ÖABT Almanca sınavının içeriği, kapsamı, alanlara göre soru dağılımı ve puan ağırlıkları incelenecek, daha sonra da Eğitim Fakültelerinin Alman Dili Eğitimi Anabilim Dallarının müfredatı ele alınacak ve böylelikle bu bölümlerde okutulan derslerin ÖABT Almanca sınavının içeriğiyle ne derece uyumlu ve sınavı kazanıp atanabilmek adına ne derece yeterli olduğu tartışılacaktır. Çanakkale Onsekiz Mart Üniversitesi lmanca Öğretmenliği öğrencileri ile yapılan anket çalışması ışığında da öğrencilerin sınava dair görüşleri ve beklentileri analiz edilmiş ve çalışmaya monte edilmiştir.
Redensarten sind für die Deutsch als Fremdsprache Studierenden im hohen Grad interpretationsbedürftig. Auch der Muttersprachler braucht für sie häufig eine nähere Erklärung, die im vorliegenden Fall formal (Redensart veraltet und wegen antisemitischer Sicht nicht verwendbar) und inhaltlich (Zusammenhänge, die kaum einer ahnt) sein muss. Redensarten können einen weitreichenden kulturellen Hintergrund haben und sie sind selbst, entsprechend analysiert, Quelle zur Sprach- und Kulturgeschichte. Die Redensart "... wie in der Judenschule" verrät uns zudem überraschenderweise etwas über die Frühform literarischer Entwicklung im Kulturprozess von der Mündlichkeit zur Schriftlichkeit.
D. Seleskovitch ve M. Lederer'in birlikte geliştirmiş oldukları Yorumlayıcı Çeviri (Anlam) Kuramı, çevirmeni merkeze koyan bir yaklaşım gösterir. Çeviriye ilişkin kuramsallaşmanın tarihine bakılırsa; önceki yüzyıllardan günümüze değin çevirmenin rolünü öne çıkaran görüş ve düşüncelere rastlanmaktadır. 90'lı yıllardan sonra belirginleşen bilişsel yaklaşımlar, alana yeni kazanımlar sağlamış, çeviribilim araştırmalarının uygulama alanına yansıyarak kültürlerarası veya dillerarası aktarımın başat aktörü olarak 'çevirmen'in bilişsel bakımdan yeniden değerlendirilmesine zemin hazırlamıştır. Bilişsel odaklı bir görünüm sergileyen çevirmen merkezli yaklaşımlar, çevirinin başarısının çevirmene bağlı olduğu görüşünden hareketle çevirmenin çeviri eylemi sırasında zihninde olup bitenlerin, bilişsel süreçlerinin işleyişinin ve dili kullanma mekanizmasının açıklığa kavuşturulmasını öngörür.
Bu çalışmanın amacı, Yorumlayıcı Çeviri Kuramı doğrultusunda 'anlama'nın koşulları olarak öne çıkan saptamaları ortaya koyarak çevirmenin sahip olması gereken özniteliklere ilişkin izdüşümleri serimlemektir. Bu amaç doğrultusunda, anlamın kavranması sürecinde çevirmenin zihinsel süreçlerinin nasıl işlediği, çevirmenin bu süreçleri nasıl yönettiği betimlenmeye ve söylem çözümlemesine dayanan Yorumlayıcı Çeviri Kuramı ve Yorumlayıcı Çeviri Yöntemi'nde yer alan düşünsel veriler görünür kılınmaya çalışılacaktır.
Eine immer dringlicher geforderte kultur- und medienwissenschaftliche Orientierung der interkulturellen Germanistik erfordert zugleich auch eine Auseinandersetzung mit neueren Konzepten, die differenzierende, dynamische und multiperspektivische Ansätze anbieten. So bemühen sich neuere kulturphilosophische Konzepte wie die Hyperkulturalität und Transdifferenz über rigide binäre Unterscheidungen zwischen "Eigenem" und "Fremden" hinauszugehen und der Durchlässigkeit der Grenzen und der internen Heterogenität von Gesellschaften im Zeitalter der Globalisierung in angemessener Weise gerecht zu werden. Vor diesem Hintergrund untersuche ich in meinem Beitrag den Film "Almanya – Willkommen in Deutschland" (Samdereli 2011) im Rahmen einer diskursiven Auseinandersetzung mit diesen Begrifflichkeiten. Entgegen bisheriger Darstellungen im so genannten türkisch-deutschen Migrantenkino fokussiert dieses Filmbeispiel verstärkt eine (postmigrantische) Perspektive, die mit tradierten Sichtweisen und Klischees bricht. Grundsätzlich soll herausgestellt werden, wie kollektive und individuelle Phänomene von Zugehörigkeit und Identitiätskonstruktion mit filmischen Mitteln dargestellt werden. Zur Diskussion gestellt soll dabei die Frage, inwiefern neuere kulturtheoretische Konzepte dabei greifen.
Bu çalışmada geleneksel Türk namus anlayışı, biçimleri ve toplumda ve ailede erkek ve kadının konumu ile görevleri üzerine etkisi tartışılacaktır. Burada özellikle, genel olarak ve göçmenlik yaşamında namus cinayetlerini teşvik eden ve bu suçun toplum tarafından görmezlikten gelinmesini sağlayan faktörler açığa çıkarılacaktır. Bu amaçla yazar, Feo Aladag'ın sosyal açıdan ilginç ve göçmenliği konu edinen ve böylece tartışmaların bir parçası olan "Die Fremde" adlı filmini ele alacaktır. Söz konusu film, gerçeğe yakın sahneleri ile gündemdeki olguyu objektif ve eleştirel olarak tartışmaktadır.
In Ernst Jüngers Werk spielt der Topos des Niemandslandes von Anfang an eine außerordentliche Rolle. Gleich ob es sich um den umkämpften Raum zwischen den erstarrten Fronten des ersten Weltkrieges, die Imagination tropischer Zonen, die Überschreitung jeder Normalität im Drogenrausch oder den Entschluß zur Desertation aus dem bürgerlichen Alltag im "Waldgang" handelt -, stets fasziniert das Niemandsland durch die Abwesenheit von Sicherheit und die Nötigung zu freier Aktion. Seinen geheimen Fluchtpunkt findet der Topos der "Terra nullius" aber in der Idee eines Schreibens, das dem Tod, dem eigentlichen Niemandsland, eine Stimme geben könnte.
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.
Türkiye'de Akademik Açık Erişim Dergi Yayıncılığı ve Çeviribilim Alanındaki Açık Erişim Dergiler
(2014)
Bu çalışmada Türkiye'nin akademik açık erişim dergi yayıncılığında geldiği noktayı ortaya koymak, 70'li yıllardan itibaren dilbilim ve filolojiden ayrılarak kendi bilimsel çerçevesini çizen ve kendi bilimsel iletişim sistemini oluşturan Çeviribilim alanının, bilimsel iletişim sisteminin en önemli araçlarından biri olan akademik açık erişim dergicilik konusunda aldığı mesafeyi görmek, bu konuda mevcut eksiklikleri tespit etmek ve bunlara çözüm önerilerinde bulunmak amaçlanmaktadır. Bu amaçla ulusal ve uluslararası açık erişim veritabanları incelenerek elde edilen bilgiler değerlendirilmeye çalışıldı. Çalışmanın birinci aşamasında Türkiye'nin akademik açık erişim dergicilik konusundaki mevcut durumu değerlendirilirken ikinci aşamada Çeviribilim alanının durumu ele alındı. Son aşamada ise elde edilen verilerden anlamlı sonuçlar çıkarılarak genel bir değerlendirme yapıldı ve çeşitli öneriler sunuldu.
Die Anwendung von Social Media im Fremdsprachenunterricht am Beispiel von "Twitter" Microblogging
(2014)
"Sosyal medya" sözcüğü günümüzün sloganı haline gelmiştir. Teknik olarak sosyal ağları destekleyen Web 2,0 hizmetlerinin uygulaması ile blog ve microblog hizmetleri her alanda kullanılmaya ve hiç olmadığı kadar iletişim kurulmaya başlanmıştır.
Twitter da, bu hizmetlerin ortak paydası olan dünyadan haberdar olma, olaylara katılma, bu amaçla da, fazla teknik bilgi gerektirmeden içerik oluşturma ve yayınlama özelliğini kullanıcılarına sunmaktadır. Nasıl ve ne şekilde iletişim kurulduğu çok farklılık göstermekle birlikte, paylaşılanlar çok basit önemsiz konuşmalardan, eğlendirici, bilgilendirici politik ve ticari içeriklere kadar uzanıp, zaman zaman da kutuplaşmalara sebep olmaktadır. Öyle ki bazıları bu içerikleri önemsiz ve gereksiz görürken, diğerleri 'devrim' yaratan nitelikte bulabilmektedir. Gerçek olan, bu kanallar aracılığı ile birçok bilginin ve içeriğin paylaşılıyor, iletişim kuruluyor olmasıdır.
Bu çalışmanın amacı Microblogging hizmeti [uygulaması] olan Twitter'ın tanıtılması, anlaşılır hale getirilmesidir. Bunu için öncelikle tarihçesi ve var olan durum açıklanmış, hesap oluşturma ve uygulamaları üzerinde durulmuştur. Ayrıca "internet dili", bu dilin gençler üzerindeki etkileri ile medya okuryazarlığının önemine ve meslek edinme sürecindeki etkilerine kısaca değinilmiştir. Son olarak örnek bir uygulama üzerinden Twitter'ın ders ortamlarında kullanılabilirlik özelliği işlenmiştir.
Eğitim, Öğretme ve Öğrenme konuları uluslararası eğitim alanında olduğu gibi Türkiye'de de son yıllarda en fazla konuşulan, tartışılan ve değişime uğrayan temadır. Öyle ki artan bilgi yoğunluğu, hızlı teknolojik kazanımlar ve buna bağlı olarak farklılaşan anlayış ve beklentiler eğitimin sürekli ve nitel açıdan irdelenmesini zorunlu kılmaktadır. Çalışmada eğitim konusunun temel sorun ve soruları, uluslararası eğitim standartları ve değişen eğitim stratejileri, öğrenme ve etkin öğretme ile ilgili yeni yaklaşımları, öğretmen tanımlamaları, öğretmen-öğrenci ve veli iletişimin önemi, öğretmen kazanımları ve yeterlilikleri gibi geniş bir perspektif taranmaktadır. Çalışmada yüksek öğretim reformu kapsamında eğitim fakülteleri ve öğretmen yetiştirme modelleri ve bu çalışmaların uluslararası uyumu değerlendirilmekte ve daha iyi bir eğitim, daha etkin öğretme ve öğrenme için öneriler sunulmaktadır.
Das Ziel dieser Arbeit ist über historische und soziale Beziehungen zwischen Brasilien und Deutschland zu diskutieren, die bei den frühesten iberischen Expeditionen im 16. Jahrhundert, bei der Entdeckung Brasiliens, stattfanden, und sich mit dem offiziellen Beginn der deutschen Auswanderung nach Brasilien, im Jahr 1824, mit der Gründung der Kolonie von São Leopoldo im Bundesstaat Rio Grande do Sul, verstärkte. Im Hinblick darauf, dass die Deutschen ihre Traditionen, Sprache und Kultur, deren Unterschiede die brasilianische Heterogenität intensivierte, nicht vollständig verloren haben, bezieht sich der zweite Teil dieses Textes auf ein konkretes Beispiel einer brasilianischen Stadt namens Marechal Câdido Rondon. Die Stadt liegt in Südbrasilien und wurde von deutschstämmigen Auswanderern gegründet. Trotz diesen germanischen Wurzeln, welche sich durchaus in der Architektur und den Volksfesten bemerkbar machen, zeigt die Gemeinde keine Auffälligkeiten hinsichtlich der deutschen Sprache aufgrund der Förderung der Zweisprachigkeit.
Das Faktum, dass in der Komikproduktion "Türkisch für Anfänger" Verhaltens- und Sprachpraktiken des türkischstämmigen männlichen Jugendlichen namens Cem Öztürk als standardfern angesehen und so dargestellt werden, und der Betroffene demnach im komischen Modus stets mit dem Affen bzw. Affenmenschen verglichen wird, wurde für die Autorin der vorliegenden Arbeit zum Auslöser für den Vergleich seiner mit Bourroughs' Protagonisten Tarzan. Dies wiederum eröffnet Reflexion und Debatte über Machtverhältnisse/Positionierungen in der deutschen Einwanderergesellschaft einen freien Raum.
Bu makalede Şebnem İşigüzel ve Elfriede Jelinek'in kitaplarından yola çıkılarak annelerin anne – kız arasındaki ilişkinin niteliklerini nasıl ve ne yönde etkiledikleri karşılaştırmalı olarak ortaya konmaya çalışılmıştır. Her iki tarafın da dişil bir kimliğe sahip olmasına rağmen, annelerin baskın otoriteleri ile bu ilişkiye şiddeti dahil etmeleri sonucu bunun kendi kızları, dolayısı ile kadın bedeni ve iç dünyası üzerindeki yansımaları ve algılanışları kitaplardan alınan alıntılarla örneklendirilmiştir. Bu örneklendirme her iki kitabın romanların ana teması, figürlerin özellikleri, belirli imgeler ile yazarın üslup özellikleri gibi başlıklar rehberliğinde gerçekleştirilmiştir.
Bellek ve tarih ilişkisinin irdelendiği bir çok araştırmada, doksanlı yılların başından beri tüm dünyada bir bellek ve anımsama furyasının yaşandığı belirtilmekte ve ana nedenlerinden biri olarak da yazılı tarihin kaydettiği en ağır felaketlerin yaşandığı 20. Yüzyılın sona ermesi gösterilmektedir. 2000'li yıllardan bu yana gerek Avrupa kıtasında yazılan romanlara gerekse Türkiye'de yayımlanan romanlara bakıldığında, metinlerin odak noktasına yakın geçmişi yerleştiren tarihsel romanların sayısı küçümsenmeyecek kadar artmıştır. Yakın tarihe bugünden bakarak tarihsel durumların yeniden değerlendirilmesi, dolayısıyla belleklerde saklanan ancak şimdi dile gelen anıların öykülendirilmesi söz konusudur.
Tarihsel romanların yanı sıra bir ya da birden fazla ailenin kuşaklar boyu belleklerinde sakladıkları ve büyük tarihin yanında bugün "oral history" olarak yeniden önem kazanan bireysel/kollektif bellek, özellikle tarihsel romanların bir uzantısı olan "yeni" aile romanlarında gittikçe daha fazla yer bulmaktadır. 2011'in Mart ayında yayımlanan, Zülfü Livanel'nin "Serenad" adlı romanı da içerdiği tarihsel düzlem ve bu tarihin bireysel ve kollektif belleklerin bir parçası olarak aile üyelerinin anımsaması yoluyla okuyucuya açımlanması nedeniyle, çerçevesini tarihsel olguların oluşturduğu bir aile romanıyla karşı karşıya olduğumuzu göstermektedir.
Bu çalışmada romanda yer alan figürlerin tarihle ilişkileri yeni aile romanı çerçevesinde incelenecektir.
Als Weltautor ist der deutsche Dichter Johann Wolfgang von Goethe mit seinen Werken "Werther" und "Faust" unumstritten ein weit beliebter und prominenter Autor des 18. Jh.s. Ein ebenso beliebtes Werk des Autors ist die Ballade vom "Erlkönig", eine typisch lyrische Gattung der deutschen Dichtung der Romantik. Dass es sich hierbei nicht um ein rein zum Tanzen gesungenes Lied handelt, sondern vielmehr eine in sich geschlossene Welt von Symbolen dargestellt wird, ist bereits dem Titel zu entnehmen.
Begriff, Bedeutung und Funktion der Figuration "Erlkönig" stehen so als Thema und Fragestellung im Mittelpunkt der Diskussion des Beitrags. Handelt es sich bei dem benannten Begriff und Titeltext um eine Inspiration Goethes aufgrund einer missverstandenen Übersetzung Herders? Oder ist unter dieser Begrifflichkeit doch ein Geisterwesen, gar ein König der Geister zu verstehen, was wiederum die Bedeutungsvielfalt und die Symbolwelt des Volkstümlich-Mythologischen als Grundwissen voraussetzt. In diesem Sinne kommt der gesamte Bedeutungskomplex des Textes dem türkischen Volksglauben vom Alkarısı (wörtlich "Rote Frau") einerseits und Karabasan (wörtlich "Schwarz-Druck") andererseits nahe, zumal der Text mit dem tragischen Schicksal des fiebernden und halluzinierenden Kindes ein Ende nimmt.
Ziel des Beitrages ist so die Aufdeckung der verschlüsselten Botschaften des Textes; Symbole, kulturelle Werte und Handlungsmuster der Textstruktur sollen im Rahmen der volkskundlich-kritischen Textanalyse unter Einbeziehung der Hermeneutik anhand von Fallbeispielen der deutschen und türkischen Volksdichtung herausgearbeitet werden.
Schiller'in Edebiyat Görüşü
(2014)
Schiller'in edebiyat üzerine yazdığı makalesi "Über naive und sentimentalische Dichtung", Goethe ile yakın ve verimli dostluğuna dayanır. Mektuplaşmalarında eserleri hakkında karşılıklı ifadeleri bunu göstermektedir. Schiller'in çıkardığı "Die Horen" adlı edebi ve felsefi dergi, Goethe'nin katkısıyla nerdeyse Alman Klasisizminin program dergisi olmuştur. Felsefeye olan büyük merakı ile Schiller Goethe'nin eserlerini ve "Horen" dergisindeki yazılarını okuyunca, kendisi ile onun arasında önemli bir farkı keşfetmek durumunda kalmıştır. Doğalcı ve düşünselci edebiyat hakkında yazdığı görüşleri bunun kanıtlarıdır.
Eine deutsche Volksballade aus Bayern mit einem Türken-Thema und ihr Verhältnis zur Geschichte
(2014)
Volksballaden sind interessante kulturhistorische Belege; sie spiegeln Zeitgeschehen und Mentalitäten – historisch sind sie nicht, auch wenn sie als 'wahr' empfundene Ereignisse aufgreifen. Die deutsche Volksballade vom "Dollinger" wurde unter dem Eindruck der über Jahrhunderte andauernden Türkengefahr überliefert und jeweils neu aktualisiert; sie hat eine in Regensburg lokalisierte Stadtsage zum Inhalt, wie ein christlicher Held nur mit Mühe den heidnischen Türken (oder Ungarn, Osmanen usw.) überwindet und damit die Stadt (das Land) rettet.
Aus dem nun mehr als sechzig Jahre zurück liegenden Streit zwischen Staiger und Heidegger über das rechte Verständnis einer Verszeile von Eduard Mörike, der im Laufe der Jahre immer neue Stellungnahmen provozierte, läßt sich Aufschluß über die blicklenkenden Kategorien hermeneutischer Interpretation gewinnen, wenn man die Position einer Beobachtung zweiter Ordnung einnimmt. Es zeigt sich dann in großer Klarheit, daß die Interpretation literarischer Polyvalenzen und Ambiguitäten ihre Eindeutigkeit aus der Zuhilfenahme regulativer Ideen gewinnt, die nicht dem literarischen Text, sondern ästhetischen Vorlieben, philosophischen Axiomen oder politisch – moralischen Überzeugungen entstammen. Sie erzielen Sinneffekte, weil sie sich mehr oder weniger erfolgreich als subjektive Setzungen unsichtbar machen und aus der "Sache" heraus zu sprechen vorgeben. Werden diese regulativen Ideen aus der Perspektive einer Beobachtung zweiter Ordnung ins Sichtfeld gerückt, erscheint die Kontingenz jeder Interpretation, die immer auch anders möglich ist. Sie hat sich freilich am Wortlaut des literarischen Werkes zu bewähren, der jedem Konstruktivismus eine unüberschreitbare Grenze setzt. So verstanden ist die berühmte und nicht selten auch bespöttelte Kontroverse zwischen Heidegger und Staiger noch heute eine anregende Hilfestellung für jeden Versuch eines neuen Verständnisses von Mörikes Gedicht und eine grundsätzliche Herausforderung der Reflexion auf die Voraussetzungen literaturwissenschaftlicher Interpretation.
Sanat ve ahlâk arasındaki ilişki Antik dönemden bu yana tartışılan en eski felsefi sorunlardan birisi olarak görülebilir. Bu iki alan arasında varolduğu düşünülen doğrudan bağı kabul etmeyen ve "çıkarsız hoşa gitme" kavramıyla sanatın özerkliğini ilan eden Kant'ın estetiğiyle birlikte sorun kısmen çözülmüştür. Sanatın özgürlüğü anlamına gelen bu ayrım 20. Yüzyılın ikinci yarısından itibaren relativizm ve postmodernizm akımlarının yardımıyla daha da kabul edilebilir hale gelmesiyle günümüzde bu iki alan arasındaki ilişkiye vurgu yapmak nerdeyse imkansız hale geldi. Jauss'un bu konudaki düşünceleri bu nedenle neredeyse bir istisnaya karşılık gelirler. Jauss'un kuramı sanat ve edebiyatı okur ve alımlayıcı açısından ele alır ve sanat ve edebiyat aracılığıyla okur ya da alımlayıcının ahlâki yargılar oluşturduklarını söyler.
This article deals with the topic of dyslexia in adults and its consequences for learning German during university studies; the author explores the extent to which an optimized German text influences understanding. The results of research on dyslexia and psycholinguistic research on text understanding show that depending on the text structure and the simplicity of the linguistic means used, different levels of text understanding may be expected. The main tool of the research is text optimization based on a practical application of the "Hamburg concept of understandability", involving four text properties which make the text understandable to different extents.
Textkompetenz in mehreren Sprachen : Forschungsergebnisse und weiterführende Forschungsansätze
(2014)
The article presents results of an empirical study which examines productive transfer in the area of text skills competence and the associated writing skill which could be attributed to the learners' contact with several languages. The research was conducted within the research project "Multilingualism in the Czech Republik: Learning and Teaching German after English." After a short presentation of the key concepts in the development of the study and a presentation of selected results, implications and a modell for further research in multilingual writing and on transfer processes between languages are introduced.
Kunigunda of Galicia, the second wife of the Bohemian King Otokar II and later the second wife of the powerful nobleman Záviš of Falkenstein, suffers from a very poor reputation due to her depiction in medieval chronicles, especially the Styrian Rhymed Chronicle written by Ottokar aus der Gaal. Her image as a domineering and morally dubious figure is also echoed in Franz Grillparzer's play "König Ottokars Glück und Ende", which draws partly on the Styrian chronicle as source material. This study attempts to answer the question of what role Kunigunda plays in Grillparzer's drama, and whether she genuinely deserves to be known as a "whore" – a designation which was applied to her immediately after the play's premiere. Grillparzer's version of Kunigunda is also compared with her depiction in the tragedy "Král Přemysl Otakar Druhý" by František Zavřel.
The unique situation in which job seekers and employers find themselves results in the necessity to formulate and accept refusal letters. Employers frequently express their emotions in such letters. They are, however, in the form of clichés which apparently do not contain any genuine emotions. The subject of this analysis is genuine German refusal letters collected in the years between 2000 and 2012. Our objective is to indicate the types of emotions verbalized in the analyzed text type and to present the linguistic means utilized to express those emotions.
The article focuses on two objectives. First it addresses current trends in the lexical development of the German language. This investigation is based on changes within the section Fernsehabend to Fernsehzuschauerin in the "Duden – Deutsches Universalwörterbuch" between 1996 and 2011. Secondly, on the basis of the given section, the article examines to what extent this dictionary reflects current vocabulary.
"Jelen přeplotil skok" : kontrastiver Vergleich von Wortspielen und idiomatischen Wortverbindungen
(2014)
The article presents some of the outcomes of the contrastive comparison of the Czech original text and its German translation. It tries to show some hidden implications as well as many other peculiarities of wordplay and idiomatic phrases that a reader of the translated text may be deprived of.
This article examines the use of the standard German language in German speaking Switzerland with focus on the spoken language. It brings to attention sociolinguistic concepts of the Swiss language environment and the role of the standard German language in Switzerland. The goal of the article is to evaluate the role of the standard German language in German speaking Switzerland on the base of theoretical assumptions and empirical research. The article presents the results of an analysis which was performed on the examples of TV broadcast of the Swiss television.
Ziel des vorliegenden Artikels ist die Analyse von Motivationsschreiben, einer Textsorte, die bei der Bewerbung um einen Masterstudienplatz oder um ein Stipendium häufig eingereicht werden muss. Anhand eines Korpus von 30 Motivationsschreiben, welche im Rahmen der Masterarbeit von November 2013 bis Mai 2014 gesammelt wurden, sollen die Relevanz, der Kommunikationskontext und die Textfunktionen der offenen Textsorte aufgezeigt werden.
O objetivo principal deste artigo é apresentar uma visão geral dos resultados obtidos em uma pesquisa empírica envolvendo aprendizes adultos de alemão como língua estrangeira com conhecimentos prévios de inglês. O foco deste artigo recai sobre os processos envolvidos no ensino/aprendizagem de terceiras línguas, levando-se em consideração que a língua alemã é comumente aprendida como uma segunda língua estrangeira após o inglês. Os principais questionamentos da pesquisa estão baseados em processos de transferência positiva, bem como na interferência linguística observada em um grupo de 50 aprendizes de alemão dos níveis A1 a B1 do Quadro Europeu Comum de Referência para as Línguas. Ao que concerne a relação entre as línguas alemã e inglesa, a afirmação de que o inglês exerce um papel importante na aprendizagem de alemão pôde ser confirmada, sendo o parentesco etimológico entre as duas línguas um dos mais importantes fatores para se determinar a ocorrência de influência interlinguística. Por outro lado, a interferência linguística resultante da coexistência de ambas as línguas demanda o desenvolvimento de uma didática do plurilinguismo que compreenda métodos alternativos para o ensino/aprendizagem de alemão como segunda língua estrangeira no Brasil.
"Great technology, football and ..." : Malaysian language learners' stereotypes about Germany
(2014)
This study focuses on stereotypes about Germany, its culture and people, held by learners of German in a big public university in Malaysia. It examines not only the stereotypical representations of the target language country but also assesses its favourability and salience, which has not been done previously. The findings revealed that the students' stereotypes about Germany were varied and diverse. Also, they were overwhelmingly positive. The top three salient categories of images about Germany were related to technology, famous personalities – for the most part football players and scientists – and cars. The findings also indicated that very few references had been made to German culture and to its great cultural figures. The results of the present study suggest that students could benefit from a wider and deeper exposure to German culture in the language classroom.
Der Aufsatz untersucht das syntaktische Verhalten nicht-satzförmiger Adverbialia im Deutschen und im brasilianischen Portugiesisch in vergleichender Perspektive. Behandelt werden Adverbialia aus sechs Klassen, deren semantische Funktionen von der Sachverhaltsbeschreibung bis zur Beschreibung von Handlungsabsichten des Sprechers reichen. Insgesamt zeigen sich große Ähnlichkeiten zwischen den Vergleichssprachen. Im Deutschen scheint eine etwas stärkere Tendenz zu bestehen, Adverbialia syntaktisch zu integrieren, während es im Portugiesischen mehr Möglichkeiten gibt, sie desintegriert zu verwenden.
Este artigo recapitula as traduções de Wilhelm Busch publicadas no Brasil e aponta que determinadas circunstâncias de publicação levaram a uma recepção unilateral de sua obra exclusivamente como literatura infantil nesse país. Entre outras estratégias que poderiam estender para uma faixa etária adulta o público leitor da poesia humorística buschiana, propõe-se que o Knittelvers seja traduzido para o português como decassílabo iâmbico. Uma tradução anotada do poema "Hänsel und Gretel" nesse padrão métrico-acentual testa em que medida a escolha consciente de um ritmo e o aproveitamento de associações culturais desencadeadas por ele podem destacar o efeito irônico desse pseudoconto-de-fada.
O presente texto lida com a forma do juízo em Hölderlin e Hegel, focalizando principalmente seus momentos de divisão e unificação. Inicialmente, unificação e divisão são aqui tratadas a partir de temáticas desenvolvidas em torno do amor no séc. XVIII. O juízo é analisado basicamente no âmbito da Ciência da lógica, de Hegel, de prefácios do romance Hyperion e do texto "Juízo e Ser", de Hölderlin. A análise visa expor as passagens entre esses momentos do juízo nos textos supracitados, as quais mobilizam relações entre singular, particular e geral. Considerando essas relações, propõe-se uma interpretação do romance acima mencionado.
A influência de Bertolt Brecht sobre Walter Benjamin é comumente atribuída à assimilação da tradição de crítica marxista pelo último. O presente artigo busca realizar uma crítica imanente e teórica da obra de ambos com o fito de investigar outras faces possíveis dessa influência. Sendo assim, o objetivo é demonstrar que o "Efeito de distanciamento" (em alemão "Verfremdungseffekt") utilizado por Brecht em seu teatro épico tem um papel fundamental na leitura que Benjamin fará do cinema e aparece nas quatro versões do ensaio sobre "A obra de arte na época de sua reprodutibilidade técnica", bem como na sua teoria sobre a "aura".
Franz Kafka's (1883-1924) "Die Brücke" is one of the less well-known texts by one of the most prolific authors of literary modernity. However, this short prose text embodies prevalent questions of literary modernity and philosophy as it reflects the crisis of language in regard of identity, communication, and literary production. Placed in the context of fin-de-siècle's discourse of language crisis, this article provides a dialogue between Kafka's "Die Brücke" and Hannah Arendt's (1906-1975) philosophy of thinking and speaking in "The Life of the Mind". Contrary to Arendt's understanding of the metaphor as "a carrying over" between the mental activities of the solitude thinker and a reconciliation with the pluralistic world shared with others, this article argues for a deconstructionist reading of "Die Brücke" as a tool to reevaluate Arendt"s notion of a shared human experience ensured through language and illustrates the advantages of poetic texts within philosophical discourses.
Seven years after the launch of the European Paediatric Medicine Regulation, limited progress in paediatric oncology drug development remains a major concern amongst stakeholders – academics, industry, regulatory authorities, parents, patients and caregivers. Restricted increases in early phase paediatric oncology trials, legal requirements and regulatory pressure to propose early Paediatric Investigation Plans (PIPs), missed opportunities to explore new drugs potentially relevant for paediatric malignancies, lack of innovative trial designs and no new incentives to develop drugs against specific paediatric targets are some unmet needs. Better access to new anti-cancer drugs for paediatric clinical studies and improved collaboration between stakeholders are essential. The Cancer Drug Development Forum (CDDF), previously Biotherapy Development Association (BDA), with Innovative Therapy for Children with Cancer Consortium (ITCC), European Society for Paediatric Oncology (SIOPE) and European Network for Cancer Research in Children and Adolescents (ENCCA) has created a unique Paediatric Oncology Platform, involving multiple stakeholders and the European Union (EU) Commission, with an urgent remit to improve paediatric oncology drug development. The Paediatric Oncology Platform proposes to recommend immediate changes in the implementation of the Regulation and set the framework for its 2017 revision; initiatives to incentivise drug development against specific paediatric oncology targets, and repositioning of drugs not developed in adults. Underpinning these changes is a strategy for mechanism of action and biology driven selection and prioritisation of potential paediatric indications rather than the current process based on adult cancer indications. Pre-competitive research and drug prioritisation, early portfolio evaluation, cross-industry cooperation and multi-compound/sponsor trials are being explored, from which guidance for innovative trial designs will be provided.
Structure and regulatory interactions of the cytoplasmic terminal domains of serotonin transporter
(2014)
Uptake of neurotransmitters by sodium-coupled monoamine transporters of the NSS family is required for termination of synaptic transmission. Transport is tightly regulated by protein–protein interactions involving the small cytoplasmic segments at the amino- and carboxy-terminal ends of the transporter. Although structures of homologues provide information about the transmembrane regions of these transporters, the structural arrangement of the terminal domains remains largely unknown. Here, we combined molecular modeling, biochemical, and biophysical approaches in an iterative manner to investigate the structure of the 82-residue N-terminal and 30-residue C-terminal domains of human serotonin transporter (SERT). Several secondary structures were predicted in these domains, and structural models were built using the Rosetta fragment-based methodology. One-dimensional 1H nuclear magnetic resonance and circular dichroism spectroscopy supported the presence of helical elements in the isolated SERT N-terminal domain. Moreover, introducing helix-breaking residues within those elements altered the fluorescence resonance energy transfer signal between terminal cyan fluorescent protein and yellow fluorescent protein tags attached to full-length SERT, consistent with the notion that the fold of the terminal domains is relatively well-defined. Full-length models of SERT that are consistent with these and published experimental data were generated. The resultant models predict confined loci for the terminal domains and predict that they move apart during the transport-related conformational cycle, as predicted by structures of homologues and by the “rocking bundle” hypothesis, which is consistent with spectroscopic measurements. The models also suggest the nature of binding to regulatory interaction partners. This study provides a structural context for functional and regulatory mechanisms involving SERT terminal domains.
Background: Despite improvements in liver surgery over the past decades, hemostasis during hepatic resections remains challenging. This multicenter randomized study compares the hemostatic effect of a collagen hemostat vs. a carrier-bound fibrin sealant after hepatic resection.
Methods: Patients scheduled for elective liver resection were randomized intraoperatively to receive either the collagen hemostat (COLL) or the carrier-bound fibrin sealant (CBFS) for secondary hemostasis. The primary endpoint was the proportion of patients with hemostasis after 3 min. Secondary parameters were the proportions of patients with hemostasis after 5 and 10 min, the total time to hemostasis, and the complication rates during a 3 months follow-up period.
Results: A total of 128 patients were included. In the COLL group, 53 out of 61 patients (86.9 %) achieved complete hemostasis within 3 min after application of the hemostat compared to 52 out of 65 patients (80.0 %) in the CBFS group. The 95 % confidence interval for this difference [−6.0 %, 19.8 %] does not include the lower noninferiority margin (−10 %). Thus, the COLL treatment can be regarded as noninferior to the comparator. The proportions of patients with hemostasis after 3, 5, and 10 min were not significantly different between the two study arms. Postoperative mortality and morbidity were similar in both treatment groups.
Conclusion: The collagen hemostat is as effective as the carrier-bound fibrin sealant in obtaining secondary hemostasis during liver resection with a comparable complication rate.
A cell-based high-throughput screen that assessed the cellular stability of a tumor suppressor protein PDCD4 (Programmed cell death 4) was used to identify a new guanidine-containing marine alkaloid mirabilin K (3), as well as the known compounds mirabilin G (1) and netamine M (2). The structures of these tricyclic guanidine alkaloids were established from extensive spectroscopic analyses. Compounds 1 and 2 inhibited cellular degradation of PDCD4 with EC50 values of 1.8 μg/mL and 2.8 μg/mL, respectively. Mirabilin G (1) and netamine M (2) are the first marine natural products reported to stabilize PDCD4 under tumor promoting conditions.
Resveratrol shows beneficial effects in inflammation-based diseases like cancer, cardiovascular and chronic inflammatory diseases. Therefore, the molecular mechanisms of the anti-inflammatory resveratrol effects deserve more attention. In human epithelial DLD-1 and monocytic Mono Mac 6 cells resveratrol decreased the expression of iNOS, IL-8 and TNF-α by reducing mRNA stability without inhibition of the promoter activity. Shown by pharmacological and siRNA-mediated inhibition, the observed effects are SIRT1-independent. Target-fishing and drug responsive target stability experiments showed selective binding of resveratrol to the RNA-binding protein KSRP, a central post-transcriptional regulator of pro-inflammatory gene expression. Knockdown of KSRP expression prevented resveratrol-induced mRNA destabilization in human and murine cells. Resveratrol did not change KSRP expression, but immunoprecipitation experiments indicated that resveratrol reduces the p38 MAPK-related inhibitory KSRP threonine phosphorylation, without blocking p38 MAPK activation or activity. Mutation of the p38 MAPK target site in KSRP blocked the resveratrol effect on pro-inflammatory gene expression. In addition, resveratrol incubation enhanced KSRP-exosome interaction, which is important for mRNA degradation. Finally, resveratrol incubation enhanced its intra-cellular binding to the IL-8, iNOS and TNF-α mRNA. Therefore, modulation of KSRP mRNA binding activity and, thereby, enhancement of mRNA degradation seems to be the common denominator of many anti-inflammatory effects of resveratrol.
Observation and tracking of fluorescently labeled molecules and particles in living cells reveals detailed information about intracellular processes on the molecular level. Whereas light microscopic particle observation is usually limited to two-dimensional projections of short trajectory segments, we report here image-based real-time three-dimensional single particle tracking in an active feedback loop with single molecule sensitivity. We tracked particles carrying only 1-3 fluorophores deep inside living tissue with high spatio-temporal resolution. Using this approach, we succeeded to acquire trajectories containing several hundred localizations. We present statistical methods to find significant deviations from random Brownian motion in such trajectories. The analysis allowed us to directly observe transitions in the mobility of ribosomal (r)RNA and Balbiani ring (BR) messenger (m)RNA particles in living Chironomus tentans salivary gland cell nuclei. We found that BR mRNA particles displayed phases of reduced mobility, while rRNA particles showed distinct binding events in and near nucleoli.
The knowledge of phenotypic variation in the European range of the highly allergenic Ambrosia artemisiifolia L. (common ragweed) is not entirely complete, even though it is an invasive species of utmost concern. We hypothesized the prevalence of phenotypic differentiations between common ragweed populations in the introduced range, and we assumed that those differentiations were related to environmental conditions at the points of origin. Using a common garden experiment, we investigated biomass allocation, growth rates, and flowering phenology of 38 European common ragweed populations originating from a major geographical gradient. We observed considerable phenotypic variation in growth parameters and flowering phenology, e.g. mean aboveground biomass varied from 23.3 to 47.3 g between the populations. We were able to relate most measured traits with environmental parameters prevailing at the points of origin. For example, early growth of ruderal populations was highly correlated with temperature and precipitation at the point of origin. Late growth and flowering phenology were highly correlated with latitude, i.e. individuals from northern populations grew smaller and flowered and dispersed their pollen and seeds up to 5 weeks earlier than individuals from southern populations. We also found a longitudinal gradient in flowering phenology which has not yet been described. The existence of such a high variability in the introduced range may facilitate further range expansion. We suggest that the correlation with environmental variables rests upon genetic variation possibly due to adaptations to the respective environment. To clarify if such adaptation results from multiple events of introduction or as evolutionary response after introduction, genetic investigations are needed.
Molecular tumour targeting has significantly improved anti-cancer protocols. Still, the addition of molecular targeting to the treatment regime has not led to a curative breakthrough. Combined mammalian target of Rapamycin (mTOR) and histone deacetylase (HDAC) inhibition has been shown not only to enhance anti-tumour potential, but also to prevent resistance development seen under mono-drug therapy. This investigation was designed to evaluate whether cross-communication exists between mTOR signalling and epigenetic events regulated by HDAC. DU-145 prostate cancer cells were treated with insulin-like growth factor (IGF) to activate the Akt-mTOR cascade or with the HDAC-inhibitor valproic acid (VPA) to induce histone H3 and H4 acetylation (aH3, aH4). Subsequently, mTOR, Rictor, Raptor, p70s6k, Akt (all: total and phosphorylated), H3 and H4 (total and acetylated) were analysed by western blotting. Both techniques revealed a link between mTOR and the epigenetic machinery. IGF activated mTOR, Rictor, Raptor, p70s6k and Akt, but also enhanced aH3 and aH4. Inversely, IGFr blockade and knock-down blocked the Akt-mTOR axis, but simultaneously diminished aH3 and aH4. VPA treatment up-regulated histone acetylation, but also activated mTOR-Akt signalling. HDAC1 and 2 knock-down revealed that the interaction with the mTOR system is initiated by histone H3 acetylation. HDAC-mTOR communication, therefore, is apparent whereby tumour-promoting (Akt/mTORhigh, aH3/aH4low) and tumour-suppressing signals (Akt/mTORlow, aH3/aH4high) are activated in parallel. Combined use of an HDAC- and mTOR inhibitor might then diminish pro-tumour effects triggered by the HDAC- (Akt/mTORhigh) or mTOR inhibitor (aH3/aH4low) alone.
Background: Following acute coronary syndrome (ACS), the risk for future cardiovascular events is high and is related to levels of low-density lipoprotein cholesterol (LDL-C) even within the setting of intensive statin treatment. Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor expression and circulating levels of LDL-C. Antibodies to PCSK9 can produce substantial and sustained reductions of LDL-C. The ODYSSEY Outcomes trial tests the hypothesis that treatment with alirocumab, a fully human monoclonal antibody to PCSK9, improves cardiovascular outcomes after ACS.
Design: This Phase 3 study will randomize approximately 18,000 patients to receive biweekly injections of alirocumab (75-150 mg) or matching placebo beginning 1 to 12 months after an index hospitalization for acute myocardial infarction or unstable angina. Qualifying patients are treated with atorvastatin 40 or 80 mg daily, rosuvastatin 20 or 40 mg daily, or the maximum tolerated and approved dose of one of these agents and fulfill one of the following criteria: LDL-C ≥ 70 mg/dL, non-high-density lipoprotein cholesterol ≥ 100 mg/dL, or apolipoprotein B ≥ 80 mg/dL. The primary efficacy measure is time to first occurrence of coronary heart disease death, acute myocardial infarction, hospitalization for unstable angina, or ischemic stroke. The trial is expected to continue until 1613 primary end point events have occurred with minimum follow-up of at least 2 years, providing 90% power to detect a 15% hazard reduction. Adverse events of special interest include allergic events and injection site reactions. Interim analyses are planned when approximately 50% and 75% of the targeted number of primary end points have occurred.
Summary: ODYSSEY Outcomes will determine whether the addition of the PCSK9 antibody alirocumab to intensive statin therapy reduces cardiovascular morbidity and mortality after ACS.
Background: HER2 status assessment is a prerequisite for the establishment of an appropriate treatment strategy in gastric cancer. Gastric cancers are very heterogeneous and separate evaluations of gene amplification and protein expression lead to uncertainties in localizing distinct clones and are time consuming. This study evaluates the equivalence of the novel method combining both gene and protein platforms on one slide.
Methods: Immunohistochemistry (IHC) and HER2 dual-colour silver in situ hybridization (SISH) as single methods (IHC/SISH) and gene-protein platform combining both methods on one slide (gene/protein) were performed in randomly collected 100 cases of gastric adenocarcinoma. Results of IHC/SISH were compared with gene/protein staining.
Results: 96 of 100 samples were assessable. In the gene/protein staining, pathologists were able to assess gene amplification and consequent protein expression at the single cell level. In comparison trials, gene amplification was observed in 14.6% by both, conventional SISH and gene/protein platform (agreement 100%; Kappa-coefficient κ = 1.0). Protein expression scores by IHC were 70.8% (0), 10.4% (1+), 9.4% (2+), and 9.4% (3+). Protein expression by gene/protein method were: 70.8% (0), 11.5% (1+), 7.3% (2+) and 10.4% (3+) of patients. There were complete concordances in IHC assessment of cases with score 0 (100.0%; κ = 1). High concordances are shown in score 1+ (98.96%; κ = 0.947) and 3+ (96.88%; κ = 0.825) cases and good concordances in 2+ cases (95.83%; κ = 0.728).
Conclusions: This novel combined platform has the advantage of being able to evaluate both gene and the protein status in the same cancer cell and may be of particular interest for research and patient's care.
Considering the review by Puspitasari and colleagues, an additional discussion of the endpoints of the Se supplementation studies described would be helpful. In our view, selenium can safely be given to selenium-deficient cancer patients prior to and during radiotherapy. Therefore, in order to help the radiation oncologist in decision making, we strongly advocate to determine the selenium status prior to and during a potential adjuvant selenium supplementation, e.g. when trying to ease the side-effects of radiation treatment or in the aftercare situation when the selenium status may become insufficient.
Irrigation intensifies land use by increasing crop yield but also impacts water resources. It affects water and energy balances and consequently the microclimate in irrigated regions. Therefore, knowledge of the extent of irrigated land is important for hydrological and crop modelling, global change research, and assessments of resource use and management. Information on the historical evolution of irrigated lands is limited. The new global Historical Irrigation Dataset (HID) provides estimates of the temporal development of the area equipped for irrigation (AEI) between 1900 and 2005 at 5 arc-minute resolution. We collected subnational irrigation statistics from various sources and found that the global extent of AEI increased from 63 million ha (Mha) in 1900 to 112 Mha in 1950 and 306 Mha in 2005. We developed eight gridded versions of time series of AEI by combining subnational irrigation statistics with different data sets on the historical extent of cropland and pasture. Different rules were applied to maximize consistency of the gridded products to subnational irrigation statistics or to historical cropland and pasture data sets. The HID reflects very well the spatial patterns of irrigated land in the western United States as shown on historical maps. Mean aridity on irrigated land increased and river discharge decreased from 1900–1950 whereas aridity decreased from 1950–2005. The dataset and its documentation are made available in an open data repository at https://mygeohub.org/publications/8 (doi:10.13019/M2MW2G).
We have isolated a cDNA coding for a putative invertebrate-type dopamine receptor (Peadop2) from P. americana brain by using a PCR-based strategy. The mRNA is present in samples from brain and salivary glands. We analyzed the distribution of the PeaDOP2 receptor protein with specific affinity-purified polyclonal antibodies. On Western blots, PeaDOP2 was detected in protein samples from brain, subesophageal ganglion, thoracic ganglia, and salivary glands. In immunocytochemical experiments, we detected PeaDOP2 in neurons with their somata being located at the anterior edge of the medulla bilaterally innervating the optic lobes and projecting to the ventro-lateral protocerebrum. In order to determine the functional and pharmacological properties of the cloned receptor, we generated a cell line constitutively expressing PeaDOP2. Activation of PeaDOP2-expressing cells with dopamine induced an increase in intracellular cAMP. In contrast, a C-terminally truncated splice variant of this receptor did not exhibit any functional property by itself. The molecular and pharmacological characterization of the first dopamine receptor from P. americana provides the basis for forthcoming studies focusing on the significance of the dopaminergic system in cockroach behavior and physiology.
Conventional radar-based image reconstruction techniques fail when they are applied to heterogeneous breast tissue, since the underlying in-breast relative permittivity is unknown or assumed to be constant. This results in a systematic error during the process of image formation. A recent trend in microwave biomedical imaging is to extract the relative permittivity from the object under test to improve the image reconstruction quality and thereby to enhance the diagnostic assessment. In this paper, we present a novel radar-based methodology for microwave breast cancer detection in heterogeneous breast tissue integrating a 3D map of relative permittivity as a priori information. This leads to a novel image reconstruction formulation where the delay-and-sum focusing takes place in time rather than range domain. Results are shown for a heterogeneous dense (class-4) and a scattered fibroglandular (class-2) numerical breast phantom using Bristol's 31-element array configuration.
Multimorbidity is a health issue mostly dealt with in primary care practice. As a result of their generalist and patient-centered approach, long-lasting relationships with patients, and responsibility for continuity and coordination of care, family physicians are particularly well placed to manage patients with multimorbidity. However, conflicts arising from the application of multiple disease oriented guidelines and the burden of diseases and treatments often make consultations challenging. To provide orientation in decision making in multimorbidity during primary care consultations, we developed guiding principles and named them after the Greek mythological figure Ariadne. For this purpose, we convened a two-day expert workshop accompanied by an international symposium in October 2012 in Frankfurt, Germany. Against the background of the current state of knowledge presented and discussed at the symposium, 19 experts from North America, Europe, and Australia identified the key issues of concern in the management of multimorbidity in primary care in panel and small group sessions and agreed upon making use of formal and informal consensus methods. The proposed preliminary principles were refined during a multistage feedback process and discussed using a case example. The sharing of realistic treatment goals by physicians and patients is at the core of the Ariadne principles. These result from i) a thorough interaction assessment of the patient’s conditions, treatments, constitution, and context; ii) the prioritization of health problems that take into account the patient's preferences – his or her most and least desired outcomes; and iii) individualized management realizes the best options of care in diagnostics, treatment, and prevention to achieve the goals. Goal attainment is followed-up in accordance with a re-assessment in planned visits. The occurrence of new or changed conditions, such as an increase in severity, or a changed context may trigger the (re-)start of the process. Further work is needed on the implementation of the formulated principles, but they were recognized and appreciated as important by family physicians and primary care researchers.
Purpose: Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa.
Materials and methods: Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested.
Results: The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading.
Conclusion: Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.
A versatile synthetic procedure is described to prepare the benzimidazole-fused 1,2,4-thiadiazoles 2a–c via a methanesulfonyl chloride initiated multistep cyclization involving the intramolecular reaction of an in-situ generated carbodiimide with a thiourea unit. The structure of the intricate heterocycle 2a was confirmed by single-crystal X-ray analysis and its mechanism of formation supported by DFT computations.
Many diseases have been described to be associated with inflammatory processes. The currently available anti-inflammatory drug therapy is often not successful or causes intolerable side effects. Thus, new anti-inflammatory substances are still urgently needed. Plants were the first source of remedies in the history of mankind. Since their chemical characterization in the 19th century, herbal bioactive compounds have fueled drug development. Also, nowadays, new plant-derived agents continuously enrich our drug arsenal (e.g., vincristine, galantamine, and artemisinin). The number of new, pharmacologically active herbal ingredients, in particular that of anti-inflammatory compounds, rises continuously. The major obstacle in this field is the translation of preclinical knowledge into evidence-based clinical progress. Human trials of good quality are often missing or, when available, are frequently not suitable to really prove a therapeutical value. This minireview will summarize the current situation of 6 very prominent plant-derived anti-inflammatory compounds: curcumin, colchicine, resveratrol, capsaicin, epigallocatechin-3-gallate (EGCG), and quercetin. We will highlight their clinical potential and/or pinpoint an overestimation. Moreover, we will sum up the planned trials in order to provide insights into the inflammatory disorders that are hypothesized to be beneficially influenced by the compound.
Background: Hypoxia-inducible factor-1α (HIF-1α) and NF-κB play important roles in the inflammatory response after hemorrhagic shock and resuscitation (H/R). Here, the role of myeloid HIF-1α in liver hypoxia, injury, and inflammation after H/R with special regard to NF-κB activation was studied.
Methods: Mice with a conditional HIF-1α knockout (KO) in myeloid cell-line and wild-type (WT) controls were hemorrhaged for 90 min ( mm Hg) and resuscitated. Controls underwent only surgical procedures.
Results: After six hours, H/R enhanced the expression of HIF-1α-induced genes vascular endothelial growth factor (VEGF) and adrenomedullin (ADM). In KO mice, this was not observed. H/R-induced liver injury in HIF-1α KO was comparable to WT. Elevated plasma interleukin-6 (IL-6) levels after H/R were not reduced by HIF-1α KO. Local hepatic hypoxia was not significantly reduced in HIF-1α KO compared to controls after H/R. H/R-induced NF-κB phosphorylation in liver did not significantly differ between WT and KO.
Conclusions: Here, deleting HIF-1α in myeloid cells and thereby in Kupffer cells was not protective after H/R. This data indicates that other factors, such as NF-κB, due to its upregulated phosphorylation in WT and KO mice, contrary to HIF-1α, are rather key modulators of inflammation after H/R in our model.
We study the effects of the recent economic crisis on firms׳ bidding behavior and markups in sealed bid auctions. Using data from Austrian construction procurements, we estimate bidders׳ construction costs within a private value auction model. We find that markups of all bids submitted decrease by 1.5 percentage points in the recent economic crisis, markups of winning bids decrease by 3.3 percentage points. We also find that without the government stimulus package this decrease would have been larger. These two pieces of evidence point to pro-cyclical markups.
Background: Since sorafenib has shown activity in different tumour types and gemcitabine regimens improved the outcome for biliary tract cancer (BTC) patients, we evaluated first-line gemcitabine plus sorafenib in a double-blind phase II study.
Patients and methods: 102 unresectable or metastatic BTC patients with histologically proven adenocarcinoma of gallbladder or intrahepatic bile ducts, Eastern Cooperative Oncology Group (ECOG) 0–2 were randomised to gemcitabine (1000 mg/m2 once weekly, first 7-weeks + 1-week rest followed by once 3-weeks + 1-week rest) plus sorafenib (400 mg twice daily) or placebo. Treatment continued until progression or unacceptable toxicity. Tumour samples were prospectively stained for sorafenib targets and potential biomarkers. Serum samples (first two cycles) were measured for vascular endothelial growth factors (VEGFs), vascular endothelial growth factor receptor 2 (VEGFR-2) and stromal cell-derived factor 1 (SDF1)α by enzyme-linked immunosorbent assay (ELISA).
Results: Gemcitabine plus sorafenib was generally well tolerated. Four and three patients achieved partial responses in the sorafenib and placebo groups, respectively. There was no difference in the primary end-point, median progression-free survival (PFS) for gemcitabine plus sorafenib versus gemcitabine plus placebo (3.0 versus 4.9 months, P = 0.859), and no difference for median overall survival (OS) (8.4 versus 11.2 months, P = 0.775). Patients with liver metastasis after resection of primary BTC survived longer with sorafenib (P = 0.019) compared to placebo. Patients who developed hand-foot syndrome (HFS) showed longer PFS and OS than patients without HFS. Two sorafenib targets, VEGFR-2 and c-kit, were not expressed in BTC samples. VEGFR-3 and Hif1α were associated with lymph node metastases and T stage. Absence of PDGFRβ expression correlated with longer PFS.
Conclusion: The addition of sorafenib to gemcitabine did not demonstrate improved efficacy in advanced BTC patients. Biomarker subgroup analysis suggested that some patients might benefit from combined treatment.
Markets are central to modern society, so their failures can have devastating effects. Here, we examine a prominent failure: price bubbles. We propose that bubbles are affected by ethnic homogeneity in the market and can be thwarted by diversity. Using experimental markets in Southeast Asia and North America, we find a marked difference: Market prices fit true values 58% better in diverse markets. In homogenous markets, overpricing is higher and traders’ errors are more correlated than in diverse markets. The findings suggest that price bubbles arise not only from individual errors or financial conditions, but also from the social context of decision making. Informing public discussion, our findings suggest that diversity facilitates friction that enhances deliberation and upends conformity.
Bacteria communicate via small diffusible molecules to mediate group-coordinated behavior, a process designated as quorum sensing. The basic molecular quorum sensing system of Gram-negative bacteria consists of a LuxI-type autoinducer synthase producing acyl-homoserine lactones (AHLs) as signaling molecules, and a LuxR-type receptor detecting the AHLs to control expression of specific genes. However, many proteobacteria possess one or more unpaired LuxR-type receptors that lack a cognate LuxI-like synthase, referred to as LuxR solos. The enteric and insect pathogenic bacteria of the genus Photorhabdus harbor an extraordinarily high number of LuxR solos, more than any other known bacteria, and all lack a LuxI-like synthase. Here, we focus on the presence and the different types of LuxR solos in the three known Photorhabdus species using bioinformatics analyses. Generally, the N-terminal signal-binding domain (SBD) of LuxR-type receptors sensing AHLs have a motif of six conserved amino acids that is important for binding and specificity of the signaling molecule. However, this motif is altered in the majority of the Photorhabdus-specific LuxR solos, suggesting the use of other signaling molecules than AHLs. Furthermore, all Photorhabdus species contain at least one LuxR solo with an intact AHL-binding motif, which might allow the ability to sense AHLs of other bacteria. Moreover, all three species have high AHL-degrading activity caused by the presence of different AHL-lactonases and AHL-acylases, revealing a high quorum quenching activity against other bacteria. However, the majority of the other LuxR solos in Photorhabdus have a N-terminal so-called PAS4-domain instead of an AHL-binding domain, containing different amino acid motifs than the AHL-sensors, which potentially allows the recognition of a highly variable range of signaling molecules that can be sensed apart from AHLs. These PAS4-LuxR solos are proposed to be involved in host sensing, and therefore in inter-kingdom signaling. Overall, Photorhabdus species are perfect model organisms to study bacterial communication via LuxR solos and their role for a symbiotic and pathogenic life style.
Ternary aerosol nucleation experiments were conducted in the CLOUD chamber at CERN in order to investigate the influence of ions on new particle formation. Neutral and ion-induced nucleation experiments, i.e., with and without the presence of ions, were carried out under precisely controlled conditions. The sulphuric acid concentration was measured with a Chemical Ionization Mass Spectrometer (CIMS) during the new particle formation experiments. The added ternary trace gases were ammonia (NH3), dimethylamine (DMA, C2H7N) or oxidised products of pinanediol (PD, C10H18O2). When pinanediol was introduced into the chamber, an increase in the mass spectrometric signal used to determine the sulphuric acid concentration (m/z 97, i.e., HSO4−) was observed due to ions from the CLOUD chamber. The enhancement was only observed during ion-induced nucleation measurements by using either galactic cosmic rays (GCR) or the proton synchrotron (PS) pion beam for the ion generation, respectively. The ion effect typically involved an increase in the apparent sulphuric acid concentration by a factor of ~2 to 3 and was qualitatively verified by the ion measurements by an Atmospheric Pressure interface-Time Of Flight (APi-TOF) mass spectrometer. By applying a high voltage (HV) clearing field inside the CLOUD chamber the ion effect on the CIMS measurement was completely eliminated since, under these conditions, small ions are swept from the chamber in about one second. In order to exclude the ion effect and to provide corrected sulphuric acid concentrations during the GCR and PS beam nucleation experiments, a parameterisation was derived that utilizes the trace gas concentrations and the UV light intensity as input parameters. Atmospheric sulphuric acid measurements with a CIMS showed an insignificant ion effect.
Ternary aerosol nucleation experiments were conducted in the CLOUD chamber at CERN in order to investigate the influence of ions on new particle formation. Neutral and ion-induced nucleation experiments, i.e. without and with the presence of ions, respectively, were carried out under precisely controlled conditions. The sulfuric acid concentration was measured with a chemical ionisation mass spectrometer (CIMS) during the new particle formation experiments. The added ternary trace gases were ammonia (NH3), dimethylamine (DMA, C2H7N) or oxidised products of pinanediol (PD, C10H18O2). When pinanediol was introduced into the chamber, an increase in the mass spectrometric signal used to determine the sulfuric acid concentration (m/z 97, i.e. HSO4−) was observed due to ions from the CLOUD chamber. The enhancement was only observed during ion-induced nucleation measurements by using either galactic cosmic rays (GCRs) or the proton synchrotron (PS) pion beam for the ion generation, respectively. The ion effect typically involved an increase in the apparent sulfuric acid concentration by a factor of ~ 2 to 3 and was qualitatively verified by the ion measurements with an atmospheric-pressure interface-time of flight (APi-TOF) mass spectrometer. By applying a high-voltage (HV) clearing field inside the CLOUD chamber, the ion effect on the CIMS measurement was completely eliminated since, under these conditions, small ions are swept from the chamber in about 1 s. In order to exclude the ion effect and to provide corrected sulfuric acid concentrations during the GCR and PS beam nucleation experiments, a parameterisation was derived that utilises the trace gas concentrations and the UV light intensity as input parameters. Atmospheric sulfuric acid measurements with a CIMS showed an insignificant ion effect.
The formation of particles from precursor vapors is an important source of atmospheric aerosol. Research at the Cosmics Leaving OUtdoor Droplets (CLOUD) facility at CERN tries to elucidate which vapors are responsible for this new particle formation, and how in detail it proceeds. Initial measurement campaigns at the CLOUD stainless-steel aerosol chamber focused on investigating particle formation from ammonia (NH3) and sulfuric acid (H2SO4). Experiments were conducted in the presence of water, ozone and sulfur dioxide. Contaminant trace gases were suppressed at the technological limit. For this study, we mapped out the compositions of small NH3-H2SO4 clusters over a wide range of atmospherically relevant environmental conditions. We covered [NH3] in the range from <2 to 1400 pptv, [H2SO4] from 3.3 × 106 to 1.4 × 109 cm−3, and a temperature range from −25 to +20 °C. Negatively and positively charged clusters were directly measured by an atmospheric pressure interface time-of-flight (APi-TOF) mass spectrometer, as they initially formed from gas-phase NH3 and H2SO4, and then grew to larger clusters containing more than 50 molecules of NH3 and H2SO4, corresponding to mobility-equivalent diameters greater than 2 nm. Water molecules evaporate from these clusters during sampling and are not observed. We found that the composition of the NH3-H2SO4 clusters is primarily determined by the ratio of gas-phase concentrations [NH3] / [H2SO4], as well as by temperature. Pure binary H2O-H2SO4 clusters (observed as clusters of only H2SO4) only form at [NH3] / [H2SO4]<0.1 to 1. For larger values of [NH3] / [H2SO4], the composition of NH3-H2SO4 clusters was characterized by the number of NH3 molecules m added for each added H2SO4 molecule n (Δm / Δn), where n is in the range 4–18 (negatively charged clusters) or 1–17 (positively charged clusters). For negatively charged clusters, Δm / Δn saturated between 1 and 1.4 for [NH3] / [H2SO4]>10. Positively charged clusters grew on average by Δm / Δn = 1.05 and were only observed at sufficiently high [NH3] / [H2SO4]. The H2SO4 molecules of these clusters are partially neutralized by NH3, in close resemblance to the acid-base bindings of ammonium bisulfate. Supported by model simulations, we substantiate previous evidence for acid-base reactions being the essential mechanism behind the formation of these clusters under atmospheric conditions and up to sizes of at least 2 nm. Our results also suggest that yet unobservable electrically neutral NH3-H2SO4 clusters grow by generally the same mechanism as ionic clusters, particularly for [NH3] / [H2SO4]>10. We expect that NH3-H2SO4 clusters form and grow also mostly by Δm / Δn>1 in the atmosphere's boundary layer, as [NH3] / [H2SO4] is mostly larger than 10. We compared our results from CLOUD with APi-TOF measurements of NH3-H2SO4 anion clusters during new particle formation in the Finnish boreal forest. However, the exact role of NH3-H2SO4 clusters in boundary layer particle formation remains to be resolved.
IKKα promotes intestinal tumorigenesis by limiting recruitment of M1-like polarized myeloid cells
(2014)
The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα) as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ)-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC) therapy.
Seven different instruments and measurement methods were used to examine the immersion freezing of bacterial ice nuclei from Snomax® (hereafter Snomax), a product containing ice active protein complexes from non-viable Pseudomonas syringae bacteria. The experimental conditions were kept as similar as possible for the different measurements. Of the participating instruments, some examined droplets which had been made from suspensions directly, and the others examined droplets activated on previously generated Snomax particles, with particle diameters of mostly a few hundred nanometers and up to a few micrometers in some cases. Data were obtained in the temperature range from −2 to −38 °C, and it was found that all ice active protein complexes were already activated above −12 °C. Droplets with different Snomax mass concentrations covering 10 orders of magnitude were examined. Some instruments had very short ice nucleation times down to below 1 s, while others had comparably slow cooling rates around 1 K min−1. Displaying data from the different instruments in terms of numbers of ice active protein complexes per dry mass of Snomax, nm, showed that within their uncertainty the data agree well with each other as well as to previously reported literature results. Two parameterizations were taken from literature for a direct comparison to our results, and these were a time dependent approach based on a contact angle distribution Niedermeier et al. (2014) and a modification of the parameterization presented in Hartmann et~al.~(2013) representing a time independent approach. The agreement between these and the measured data were good, i.e. they agreed within a temperature range of 0.6 K or equivalently a range in nm of a factor of 2. From the results presented herein, we propose that Snomax, at least when carefully shared and prepared, is a suitable material to test and compare different instruments for their accuracy of measuring immersion freezing.
Immersion freezing is the most relevant heterogeneous ice nucleation mechanism through which ice crystals are formed in mixed-phase clouds. In recent years, an increasing number of laboratory experiments utilizing a variety of instruments have examined immersion freezing activity of atmospherically relevant ice nucleating particles (INPs). However, an inter-comparison of these laboratory results is a difficult task because investigators have used different ice nucleation (IN) measurement methods to produce these results. A remaining challenge is to explore the sensitivity and accuracy of these techniques and to understand how the IN results are potentially influenced or biased by experimental parameters associated with these techniques.
Within the framework of INUIT (Ice Nucleation research UnIT), we distributed an illite rich sample (illite NX) as a representative surrogate for atmospheric mineral dust particles to investigators to perform immersion freezing experiments using different IN measurement methods and to obtain IN data as a function of particle concentration, temperature (T), cooling rate and nucleation time. Seventeen measurement methods were involved in the data inter-comparison. Experiments with seven instruments started with the test sample pre-suspended in water before cooling, while ten other instruments employed water vapor condensation onto dry-dispersed particles followed by immersion freezing. The resulting comprehensive immersion freezing dataset was evaluated using the ice nucleation active surface-site density (ns) to develop a representative ns(T) spectrum that spans a wide temperature range (−37 °C < T < −11 °C) and covers nine orders of magnitude in ns.
Our inter-comparison results revealed a discrepancy between suspension and dry-dispersed particle measurements for this mineral dust. While the agreement was good below ~ −26 °C, the ice nucleation activity, expressed in ns, was smaller for the wet suspended samples and higher for the dry-dispersed aerosol samples between about −26 and −18 °C. Only instruments making measurement techniques with wet suspended samples were able to measure ice nucleation above −18 °C. A possible explanation for the deviation between −26 and −18 °C is discussed. In general, the seventeen immersion freezing measurement techniques deviate, within the range of about 7 °C in terms of temperature, by three orders of magnitude with respect to ns. In addition, we show evidence that the immersion freezing efficiency (i.e., ns) of illite NX particles is relatively independent on droplet size, particle mass in suspension, particle size and cooling rate during freezing. A strong temperature-dependence and weak time- and size-dependence of immersion freezing efficiency of illite-rich clay mineral particles enabled the ns parameterization solely as a function of temperature. We also characterized the ns (T) spectra, and identified a section with a steep slope between −20 and −27 °C, where a large fraction of active sites of our test dust may trigger immersion freezing. This slope was followed by a region with a gentler slope at temperatures below −27 °C. A multiple exponential distribution fit is expressed as ns(T) = exp(23.82 × exp(−exp(0.16 × (T + 17.49))) + 1.39) based on the specific surface area and ns(T) = exp(25.75 × exp(−exp(0.13 × (T + 17.17))) + 3.34) based on the geometric area (ns and T in m−2 and °C, respectively). These new fits, constrained by using an identical reference samples, will help to compare IN measurement methods that are not included in the present study and, thereby, IN data from future IN instruments.
Serial quantification of BCR–ABL1 mRNA is an important therapeutic indicator in chronic myeloid leukaemia, but there is a substantial variation in results reported by different laboratories. To improve comparability, an internationally accepted plasmid certified reference material (CRM) was developed according to ISO Guide 34:2009. Fragments of BCR–ABL1 (e14a2 mRNA fusion), BCR and GUSB transcripts were amplified and cloned into pUC18 to yield plasmid pIRMM0099. Six different linearised plasmid solutions were produced with the following copy number concentrations, assigned by digital PCR, and expanded uncertainties: 1.08±0.13 × 106, 1.08±0.11 × 105, 1.03±0.10 × 104, 1.02±0.09 × 103, 1.04±0.10 × 102 and 10.0±1.5 copies/μl. The certification of the material for the number of specific DNA fragments per plasmid, copy number concentration of the plasmid solutions and the assessment of inter-unit heterogeneity and stability were performed according to ISO Guide 35:2006. Two suitability studies performed by 63 BCR–ABL1 testing laboratories demonstrated that this set of 6 plasmid CRMs can help to standardise a number of measured transcripts of e14a2 BCR–ABL1 and three control genes (ABL1, BCR and GUSB). The set of six plasmid CRMs is distributed worldwide by the Institute for Reference Materials and Measurements (Belgium) and its authorised distributors (https://ec.europa.eu/jrc/en/reference-materials/catalogue/; CRM code ERM-AD623a-f).
Myelodysplastic syndromes (MDSs) represent clonal disorders mainly of the elderly that are characterized by ineffective hematopoiesis and an increased risk of transformation into acute myeloid leukemia. The pathogenesis of MDS is thought to evolve from accumulation and selection of specific genetic or epigenetic events. Emerging evidence indicates that MDS is not solely a hematopoietic disease but rather affects the entire bone marrow microenvironment, including bone metabolism. Many of these cells, in particular mesenchymal stem and progenitor cells (MSPCs) and osteoblasts, express a number of adhesion molecules and secreted factors that regulate blood regeneration throughout life by contributing to hematopoietic stem and progenitor cell (HSPC) maintenance, self-renewal and differentiation. Several endocrine factors, such as erythropoietin, parathyroid hormone and estrogens, as well as deranged iron metabolism modulate these processes. Thus, interactions between MSPC and HSPC contribute to the pathogenesis of MDS and associated pathologies. A detailed understanding of these mechanisms may help to define novel targets for diagnosis and possibly therapy. In this review, we will discuss the scientific rationale of "osteohematology" as an emerging research field in MDS and outline clinical implications.
Background: In an earlier study we demonstrated the feasibility to create tissue engineered venous scaffolds in vitro and in vivo. In this study we investigated the use of tissue engineered constructs for ureteral replacement in a long term orthotopic minipig model. In many different projects well functional ureretal tissue was established using tissue engineering in animals with short-time follow up (12 weeks). Therefore urothelial cells were harvested from the bladder, cultured, expanded in vitro, labelled with fluorescence and seeded onto the autologous veins, which were harvested from animals during a second surgery. Three days after cell seeding the right ureter was replaced with the cell-seeded matrices in six animals, while further 6 animals received an unseeded vein for ureteral replacement. The animals were sacrificed 12, 24, and 48 weeks after implantation. Gross examination, intravenous pyelogram (IVP), H&E staining, Trichrome Masson's Staining, and immunohistochemistry with pancytokeratin AE1/AE3, smooth muscle alpha actin, and von Willebrand factor were performed in retrieved specimens.
Results: The IVP and gross examination demonstrated that no animals with tissue engineered ureters and all animals of the control group presented with hydronephrosis after 12 weeks. In the 24-week group, one tissue engineered and one unseeded vein revealed hydronephrosis. After 48 weeks all tissue engineered animals and none of the control group showed hydronephrosis on the treated side. Histochemistry and immunohistochemistry revealed a multilayer of urothelial cells attached to the seeded venous grafts.
Comclusions: Venous grafts may be a potential source for ureteral reconstruction. The results of so far published ureteral tissue engineering projects reveal data up to 12 weeks after implantation. Even if the animal numbers of this study are small, there is an increasing rate of hydronephrosis revealing failure of ureteral tissue engineering with autologous matrices in time points longer than 3 months after implantation. Further investigations have to prove adequate clinical outcome and appropriate functional long-term results.
In this study we show how size-resolved measurements of aerosol particles and cloud condensation nuclei (CCN) can be used to characterize the supersaturation of water vapor in a cloud. The method was developed and applied during the ACRIDICON-Zugspitze campaign (17 September to 4 October 2012) at the high-Alpine research station Schneefernerhaus (German Alps, 2650 m a.s.l.). Number size distributions of total and interstitial aerosol particles were measured with a scanning mobility particle sizer (SMPS), and size-resolved CCN efficiency spectra were recorded with a CCN counter system operated at different supersaturation levels.
During the evolution of a cloud, aerosol particles are exposed to different supersaturation levels. We outline and compare different estimates for the lower and upper bounds (Slow, Shigh) and the average value (Savg) of peak supersaturation encountered by the particles in the cloud. A major advantage of the derivation of Slow and Savg from size-resolved CCN efficiency spectra is that it does not require the specific knowledge or assumptions about aerosol hygroscopicity that are needed to derive estimates of Slow, Shigh, and Savg from aerosol size distribution data. For the investigated cloud event, we derived Slow ≈ 0.07–0.25%, Shigh ≈ 0.86–1.31% and Savg ≈ 0.42–0.68%.
The three-dimensional quantification of small scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe and TACTS/ESMVal aircraft campaigns. The focus of this work is on the so-called dynamics mode data characterized by a medium spectral and a very high spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3 and CFC-12) and their spatial resolution are discussed. During ESSenCe, high resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in-situ data indicate a good agreement between the data sets. During TACTS/ESMVal a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere has been performed. This filament could be reconstructed with an unprecedented spatial resolution of better than 500 m vertically and 20 km × 20 km horizontally.
In the present work, three different techniques are used to separate ice-nucleating particles (INP) and ice particle residuals (IPR) from non-ice-active particles: the Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI), which sample ice particles from mixed phase clouds and allow for the analysis of the residuals, as well as the combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Virtual Impactor (IN-PCVI), which provides ice-activating conditions to aerosol particles and extracts the activated ones for analysis. The collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine their size, chemical composition and mixing state. Samples were taken during January/February 2013 at the High Alpine Research Station Jungfraujoch. All INP/IPR-separating techniques had considerable abundances (median 20–70%) of contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH + IN-PCVI: steel particles). Also, potential measurement artifacts (soluble material) occurred (median abundance < 20%). After removal of the contamination particles, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Minor types include soot and Pb-bearing particles. Sea-salt and sulfates were identified by all three methods as INP/IPR. Lead was identified in less than 10% of the INP/IPR. It was mainly present as an internal mixture with other particle types, but also external lead-rich particles were found. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also sampled many submicron particles. Probably owing to the different meteorological conditions, the INP/IPR composition was highly variable on a sample to sample basis. Thus, some part of the discrepancies between the different techniques may result from the (unavoidable) non-parallel sampling. The observed differences of the particles group abundances as well as the mixing state of INP/IPR point to the need of further studies to better understand the influence of the separating techniques on the INP/IPR chemical composition.
Comparing two methods of determining infiltration rates of permeable interlocking concrete pavers
(2014)
Adequate infiltration through Permeable Interlocking Concrete Pavements (PICPs) is critical to their hydraulic performance. Detected by monitoring infiltration performance, reduced infiltration rates can indicate that maintenance is required. Measurement of infiltration rates has previously been problematic on PICPs because of a lack of accepted standard methodologies and the practical difficulties in modifying existing testing methodologies. On large sites, standard methodologies necessitate multiple measurements to achieve accuracy. Standard methods also contend with practical issues such as sealing the rings to the surface to prevent lateral water flow. This study examined the performance of two PICP surface infiltration rate measurement methods: a modified double-ring infiltrometer (DRIT), and a specially designed rainfall simulation infiltrometer (RSIT). A positive correlation (R2 = 0.85) of results was found between the two, demonstrating that the RSIT was comparable to the DRIT. The modified DRIT produced surface infiltration results approximately 60% higher than the RSIT results. The RSIT provided lower variation between tests, requiring fewer measurements in large sites whilst still maintaining accuracy, thereby improving testing efficiency. The new RSIT method also eliminates some of the practical difficulties with existing methodologies such as unrealistic pressure heads artificially increasing infiltration rates, and the use of sealant under test measurement infiltration rings.
Global warming, changes in the hydrological cycle and enhanced marine primary productivity all have been invoked to have contributed to the occurrence of widespread ocean anoxia during the Cenomanian-Turonian Oceanic Anoxic Event (OAE2; ~ 94 Ma), but disentangling these factors on a regional scale has remained problematic. We generated palynological and organic geochemical records that allow the separation of these forcing factors in a core spanning the OAE2 from Wunstorf, Lower Saxony Basin (LSB; North Gemany), which exhibits cyclic black shale–marl alternations related to the orbital precession cycle.
Despite the widely varying depositional conditions complicating the interpretation of the obtained records, TEX86H indicates that sea-surface temperature (SST) evolution in the LSB during OAE2 resembles that of previously studied sites throughout the proto-North Atlantic. Cooling during the so-called Plenus Cold Event interrupted black shale deposition during the early stages of OAE2. However, TEX86 does not vary significantly across marl–black shale alternations, suggesting that temperature variations did not force the formation of the cyclic black shale horizons. Relative (i.e., with respect to marine palynomorphs) and absolute abundances of pollen and spores are elevated during phases of black shale deposition, indicative of enhanced precipitation and run-off. High abundances of cysts from inferred heterotrophic and euryhaline dinoflagellates supports high run-off, which likely introduced additional nutrients to the epicontinental shelf resulting in elevated marine primary productivity.
We conclude that orbitally-forced enhanced precipitation and run-off, in tandem with elevated marine primary productivity, were critical in cyclic black shale formation on the northwest European epicontinental shelf and potentially for other OAE2 sections in the proto-Atlantic and Western Interior Seaway at similar latitudes as well.
The forest, savanna, and grassland biomes, and the transitions between them, are expected to undergo major changes in the future, due to global climate change. Dynamic Global Vegetation Models (DGVMs) are very useful to understand vegetation dynamics under present climate, and to predict its changes under future conditions. However, several DGVMs display high uncertainty in predicting vegetation in tropical areas. Here we perform a comparative analysis of three different DGVMs (JSBACH, LPJ-GUESS-SPITFIRE and aDGVM) with regard to their representation of the ecological mechanisms and feedbacks that determine the forest, savanna and grassland biomes, in an attempt to bridge the knowledge gap between ecology and global modelling. Model outcomes, obtained including different mechanisms, are compared to observed tree cover along a mean annual precipitation gradient in Africa. Through these comparisons, and by drawing on the large number of recent studies that have delivered new insights into the ecology of tropical ecosystems in general, and of savannas in particular, we identify two main mechanisms that need an improved representation in the DGVMs. The first mechanism includes water limitation to tree growth, and tree-grass competition for water, which are key factors in determining savanna presence in arid and semi-arid areas. The second is a grass-fire feedback, which maintains both forest and savanna occurrences in mesic areas. Grasses constitute the majority of the fuel load, and at the same time benefit from the openness of the landscape after fires, since they recover faster than trees. Additionally, these two mechanisms are better represented when the models also include tree life stages (adults and seedlings), and distinguish between fire-prone and shade-tolerant savanna trees, and fire-resistant and shade-intolerant forest trees. Including these basic elements could improve the predictive ability of the DGVMs, not only under current climate conditions but also and especially under future scenarios.
The Tarim River Basin, located in Xinjiang, NW China, is the largest endorheic river basin of China and one of the largest in whole Central Asia. Due to the extremely arid climate with an annual precipitation of less than 100 mm, the water supply along the Aksu and Tarim River solely depends on river water. This applies for anthropogenic activities (e.g. agriculture) as well as for the natural ecosystems so that both compete for water. The on-going increase of water consumption by agriculture and other human activities in this region has been enhancing the competition for water between human needs and nature. Against this background, 11 German and 6 Chinese universities and research institutes formed the consortium SuMaRiO (www.sumario.de), which aims at gaining a holistic picture of the availability of water resources in the Tarim River Basin and the impacts on anthropogenic activities and natural ecosystems caused by the water distribution within the Tarim River Basin. The discharge of the Aksu River, which is the major tributary to the Tarim, has been increasing over the past 6 decades due to enhanced glacier melt. Alone from 1989 to 2011, the area under agriculture more than doubled. Thereby, cotton became the major crop and there was a shift from small-scale farming to large-scale intensive farming. The major natural ecosystems along the Aksu and Tarim River are riparian ecosystems: Riparian (Tugai) forests, shrub vegetation, reed beds, and other grassland. Within the SuMaRiO Cluster the focus was laid on the Tugai forests, with Populus euphratica as dominant tree, because the most productive and species-rich natural ecosystems can be found among those forests. On sites with groundwater distance of less than 7.5 m the annual increments correlated with river runoffs of the previous year. But, the further downstream along the Tarim River, the more the natural river dynamics ceased, which impacts on the recruitment of Populus euphratica. Household surveys revealed that there is a considerable willingness to pay for conservation of those riparian forests with the mitigation of dust and sandstorms considered as the most important ecosystem service. This interdisciplinary project will result in a decision support tool (DST), build on the participation of regional stakeholders and models based on results and field experiments. This DST finally shall assist stakeholders in balancing the water competition acknowledging the major external effects of any water allocation.
Ein "hundertjähriger Krieg"? : über die Bildung einer Friedenskultur aus dem Geist des Krieges
(2014)
Wer nicht direkt Zeitgenosse im Jahre 1914 gewesen ist, kommt [...] nicht ohne Konstrukte und Nacherzählungen aus. Aber nicht nur das: Auch wer Zeitgenosse gewesen ist, mag die späteren Generationen mit Formen von Distanzierung überraschen, wie etwa Kafka mit seiner Tagebucheintragung vom 1. August 1914: "Deutschland hat Russland den Krieg erklärt. Nachmittag Schwimmschule" [...]. Nun wissen wir auch, dass Kafkas Werk einer "furchtbaren Welt" entspricht, indem sie "strukturell der Wirklichkeit, die wir zu erleben gezwungen wurden, unheimlich adäquat ist" [...]. Einer formneutralen Aufzeichnung wie derjenigen Kafkas bräuchte prinzipiell kein weiterer bedeutungsschwerer Charakter beigemessen zu werden. Jedoch könnte eine solche Aufzeichnung auch auf die Dynamik einer Kriegs- bzw. Friedenskultur hindeuten. Diese Dynamik hat nach der hier verfolgten Perspektive einen strukturellen Zusammenhang beider Kulturmuster als Spielarten, die allzu oft nur als Polaritäten, dementsprechend als Kontraste, angesehen werden. [...] Die hier vorgenommene Analyse einer solchen Problematik beinhaltet drei Schritte: 1. Die Auffächerung von Krieg und Frieden als Momente im unvollendeten Prozess der Zivilisation; 2. Thomas Manns retrospektiver Blick auf Kontraste und Spielarten, und 3. Jenseits von "kaltem Krieg", "heißem Frieden" und "blauäugigem" Pazifismus: "Ich will verstehen" oder die Rolle der Zwischenräume.
Der vorliegende Beitrag geht von der Fiktionalisierung des Ersten Weltkrieges in Remarques Erfolgsroman "Im Westen nichts Neues" (1929) aus und erforscht die literarische Funktionalisierung der Kriegsrepräsentation für Friedensdiskurse. "Zeit zu leben und Zeit zu sterben" (1954) enthält pazifistische Indizien, so dass Remarques Poetik des Friedens um die Darstellung der beiden Weltkriege strukturiert ist. In seinem Werk "Der seltsame Krieg" (2000) artikuliert der österreichische Schriftsteller Martin Auer seine Fiktion des Krieges um eine globale Sehnsucht nach Frieden, die auch neue Kriegsformen einschließt. So erhält der Signifikant "Krieg" eine dynamische Sinndeutung in der Konstruktion des Friedensdiskurses. Der Beitrag analysiert die klassischen Repräsentationen des Krieges und erkundet die Grundrisse einer Poetik des Friedens bei Erich Maria Remarque und Martin Auer.
In den Jahren 1912-1914 gelang es dem Deutschen Botschafter Karl Max Lichnowsky (1860-1928) und seiner Gattin, der Schriftstellerin Mechtilde Lichnowsky (1879-1958), die Botschafter-Residenz Carlton House Terrace zu einem Mittelpunkt des damaligen Londoner Kulturlebens und der Avantgarde zu verwandeln. Mechtilde Lichnowsky hatte mit ihrem ersten Buch "Götter, Könige und Tiere in Ägypten" (1913) einiges Aufsehen erregt und arbeitete in der Botschaft an ihrem zweiten Manuskript, dem Drama "Das Spiel mit dem Tod" (1915). Sie war eng mit Roger Fry befreundet und arbeitete in der britischen Avantgarde-Bewegung mit. Karl Max Lichnowsky bemühte sich bis zuletzt, den Krieg auf diplomatischem Wege zu verhindern. Die Mission der beiden Kosmopoliten scheiterte.
Ähnlich wie in anderen Krieg führenden Ländern war gerade die großstädtische Bevölkerung von Kriegseuphorie und einer spontanen Bereitschaft getragen, sich in den Dienst des Kriegs zu stellen. Das bald auch im Krieg florierende Unterhaltungstheater der meisten europäischen Metropolen zeigte geradezu mustergültig diese patriotisch-affirmative Tendenz. Doch in einem Land wie Portugal, in dem wenige Jahre zuvor durch eine vom städtischen liberalen Bürgertum getragene Revolution eine laizistische Republik nach französischem Vorbild installiert wurde, die noch einigermaßen instabil war, folgte die Unterhaltungskultur nicht dieser Art von patriotischer Gleichschaltung sondern bewahrte sich durchaus – besonders im Genre der Revue – satirische und kritische Eigenheiten.
Um Wedekinds politisches Engagement und Denken am Vorabend und während des Ersten Weltkriegs zu verstehen, bedarf es zunächst einer Rückschau, denn so sehr auch individuelle politische Äußerungen sich auf ein aktuelles Tagesgeschehen beziehen, sind sie doch nicht nur allein aus diesem Kontext heraus zu verstehen.
Zu Beginn noch Treffpunkt ausziehender Soldaten, die besonders in den ersten Monaten umjubelt die Städte verließen, wurde der Heimtransport Verwundeter besonders in den Grenzregionen mit zunehmender Dauer alltäglicher. Spätestens mit Kriegsende aber wird die Figur des Kriegsheimkehrers auch in den von der Westfront entfernten Städten wie Hamburg oder Berlin immer präsenter — als körperlich invalider Krüppel, wie auch als äußerlich unverletzter, aber tief traumatisierter Veteran.