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AMP-activated protein kinase (AMPK) is frequently reported to phosphorylate Ser1177 of the endothelial nitric-oxide synthase (eNOS), and therefore, is linked with a relaxing effect. However, previous studies failed to consistently demonstrate a major role for AMPK on eNOS-dependent relaxation. As AMPK also phosphorylates eNOS on the inhibitory Thr495 site, this study aimed to determine the role of AMPKα1 and α2 subunits in the regulation of NO-mediated vascular relaxation. Vascular reactivity to phenylephrine and acetylcholine was assessed in aortic and carotid artery segments from mice with global (AMPKα−/−) or endothelial-specific deletion (AMPKαΔEC) of the AMPKα subunits. In control and AMPKα1-depleted human umbilical vein endothelial cells, eNOS phosphorylation on Ser1177 and Thr495 was assessed after AMPK activation with thiopental or ionomycin. Global deletion of the AMPKα1 or α2 subunit in mice did not affect vascular reactivity. The endothelial-specific deletion of the AMPKα1 subunit attenuated phenylephrine-mediated contraction in an eNOS- and endothelium-dependent manner. In in vitro studies, activation of AMPK did not alter the phosphorylation of eNOS on Ser1177, but increased its phosphorylation on Thr495. Depletion of AMPKα1 in cultured human endothelial cells decreased Thr495 phosphorylation without affecting Ser1177 phosphorylation. The results of this study indicate that AMPKα1 targets the inhibitory phosphorylation Thr495 site in the calmodulin-binding domain of eNOS to attenuate basal NO production and phenylephrine-induced vasoconstriction.
Platelets participate in the development of liver fibrosis in animal models, but little is known about the benefit of antiplatelet agents in preventing liver fibrosis in humans. We therefore explored the relationship between the use of antiplatelet agents and liver fibrosis in a prospective cohort study of patients at high risk of liver fibrosis and cardiovascular events. Consecutive patients undergoing elective coronary angiography at the University Hospital Frankfurt were prospectively included in the present study. Associations between use of antiplatelet agents (acetyl salicylic acid, P2Y12 receptor antagonists) and liver fibrosis were assessed in regression models, and the relationship between platelet‐derived growth factor beta (PDGF‐β) serum concentration, platelets, liver fibrosis, and use of antiplatelet agents was characterized. Out of 505 included patients, 337 (67%) received antiplatelet agents and 134 (27%) had liver fibrosis defined as a FibroScan transient elastography (TE) value ≥7.9 kPa. Use of antiplatelet agents was inversely associated with the presence of liver fibrosis in univariate and multivariate analyses (multivariate odds ratio [OR], 0.67; 95% confidence interval [CI], 0.51‐0.89; P = 0.006). Use of antiplatelet agents was also inversely associated with FibroTest values (beta, –0.38; SD beta, 0.15; P = 0.02). Furthermore, there was a significant correlation between platelet counts and PDGF‐β serum concentration (rho, 0.33; P < 0.0001), but PDGF‐β serum levels were not affected by antiplatelet agents. Conclusion: There is a protective association between the use of antiplatelet agents and occurrence of liver fibrosis. A randomized controlled trial is needed to explore causality and the potential of antiplatelet agents as antifibrotic therapy in patients at risk for liver fibrosis progression.
Adult neurogenesis is regulated by stem cell niche-derived extrinsic factors and cell-intrinsic regulators, yet the mechanisms by which niche signals impinge on the activity of intrinsic neurogenic transcription factors remain poorly defined. Here, we report that MEIS2, an essential regulator of adult SVZ neurogenesis, is subject to posttranslational regulation in the SVZ olfactory bulb neurogenic system. Nuclear accumulation of MEIS2 in adult SVZ-derived progenitor cells follows downregulation of EGFR signaling and is modulated by methylation of MEIS2 on a conserved arginine, which lies in close proximity to nested binding sites for the nuclear export receptor CRM1 and the MEIS dimerization partner PBX1. Methylation impairs interaction with CRM1 without affecting PBX1 dimerization and thereby allows MEIS2 nuclear accumulation, a prerequisite for neuronal differentiation. Our results describe a form of posttranscriptional modulation of adult SVZ neurogenesis whereby an extrinsic signal fine-tunes neurogenesis through posttranslational modification of a transcriptional regulator of cell fate.
Vismodegib, an inhibitor of the Hedgehog signaling pathway, is an approved drug for monotherapy in locally advanced or metastatic basal cell carcinoma (BCC). Data on combined modality treatment by vismodegib and radiation therapy, however, are rare. In the present study, we examined the radiation sensitizing effects of vismodegib by analyzing viability, cell cycle distribution, cell death, DNA damage repair and clonogenic survival in three-dimensional cultures of a BCC and a head and neck squamous cell carcinoma (HNSCC) cell line. We found that vismodegib decreases expression of the Hedgehog target genes glioma-associated oncogene homologue (GLI1) and the inhibitor of apoptosis protein (IAP) Survivin in a cell line- and irradiation-dependent manner, most pronounced in squamous cell carcinoma (SCC) cells. Furthermore, vismodegib significantly reduced proliferation in both cell lines, while additional irradiation only slightly further impacted on viability. Analyses of cell cycle distribution and cell death induction indicated a G1 arrest in BCC and a G2 arrest in HNSCC cells and an increased fraction of cells in SubG1 phase following combined treatment. Moreover, a significant rise in the number of phosphorylated histone-2AX/p53-binding protein 1 (γH2AX/53BP1) foci in vismodegib- and radiation-treated cells was associated with a significant radiosensitization of both cell lines. In summary, these findings indicate that inhibition of the Hedgehog signaling pathway may increase cellular radiation response in BCC and HNSCC cells.
Using photo elicitation to introduce a network perspective on attachment during middle childhood
(2018)
In this article, we develop a child-centered network approach to attachment during middle childhood. Following monotropic ideas, current attachment research focuses on parental attachment figures despite the expansion of the children’s social environment during middle childhood, failing to generate a comprehensive and structured overview of all individuals who ensure the children’s feeling of safety. Relying on quantitative methods, these studies are also dominated by an adult perspective, limiting the children’s contributions. While there have been theoretical drafts of attachment networks during childhood, this article constitutes the first practical implementation. Using photo elicitation interviews and participant observations, we developed an innovative assessment strategy that allows children to exhaustively identify and characterize all their attachment figures on sociostructural and functional dimensions, thus positioning the children at the center of their comprehensive attachment networks that collectively contribute to their feeling of security. We combine qualitative and quantitative data to assess the children’s own understanding of their feeling of security and to locate the individual attachment figure on context-specific social dimensions, thus making the research setting, a clan in Cameroon, an inherent part of the methodological development. The data are translated into multidimensional network diagrams to visualize the children’s perception of their attachment environment and the emerging patterns of their selection. We present an exemplary network, supplementing it with observational data to discuss the ecological validity of our approach.
Comparative proteomics reveals a diagnostic signature for pulmonary head‐and‐neck cancer metastasis
(2018)
Patients with head‐and‐neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head‐and‐neck (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518 proteins were found to be differentially expressed between SQCLC and HNSCC, and some of these were identified as genetic dependencies in either of the two tumour types. Using supervised machine learning, we inferred a proteomic signature for the classification of squamous cell carcinomas as either SQCLC or HNSCC, with diagnostic accuracies of 90.5% and 86.8% in cross‐ and independent validations, respectively. Furthermore, application of this signature to a cohort of pulmonary squamous cell carcinomas of unknown origin leads to a significant prognostic separation. This study not only provides a diagnostic proteomic signature for classification of secondary lung tumours in HNSCC patients, but also represents a proteomic resource for HNSCC and SQCLC.
The multi-valence nature of vanadium means that its geochemical behaviour will be ƒO2-dependent, so that its concentration or V/Sc (or V/Ga), can serve as proxies for oxidation state in mantle peridotites. Compared to Fe3+/Fe2+-based equilibria, such trace elements may be less sensitive to metasomatic processes. To investigate these systematics, we have measured V, Sc, Ga and Fe3+ contents in clinopyroxene from well-characterised spinel peridotite xenoliths from the Massif Central, France. These samples were metasomatised by a variety of agents with different oxidation states.V contents can be modified by metasomatic interactions, and other geochemically similar elements including Sc and Ga can also be added, removed or remain constant. A link between V/Sc and Fe3+-Fe2+ equilibria is apparent. Partial removal of V is caused by different metasomatic agents; the common factor is that all agents were significantly more oxidised than the initial ambient mantle peridotite. This extraction can be understood by a decreasing partition coefficient for V for ΔlogƒO2 > ~FMQ-2. Considering that mineral/melt partitioning of V decreases similarly for all peridotite minerals, the bulk-rock V/Sc will also change during relatively oxidising metasomatic interactions and mirror the results obtained for clinopyroxene.
Latent myofascial trigger points (MTrP) have been linked to several impairments of muscle function. The present study was conducted in order to examine whether a single bout of self-myofascial release using a foam roller is effective in reducing MTrP sensitivity. Fifty healthy, pain-free subjects (26.8±6 years, 21 men) with latent MTrP in the lateral gastrocnemius muscle were included in the randomized, controlled trial. One week after a familiarization session, they were randomly allocated to three groups: (1) static compression of the most sensitive MTrP using a foam roll, (2) slow dynamic foam rolling of the lateral calf and (3) placebo laser acupuncture of the most sensitive MTrP. Treatment duration in each group was 90 seconds. The pressure pain threshold (PPT) of the most sensitive MTrP was assessed using a handheld algometer prior to and after the intervention. A repeated measures analysis of variance (3x2) did not reveal significant between‑group interactions (p>.05) but showed a significant time effect (F=7.715, p<.05). While placebo and dynamic selfmyofascial release did not change MTrP sensitivity (p>.05), static compression of MTrP increased the PPT (2.6±0.8 to 3.0±1.1, d=.35; p<.05). Static self-myofascial release using a foam roller might represent an alternative to reduce pressure pain of latent MTrP. Additional research should aim to extend these findings to patients and athletes with myofascial pain syndromes.
Fungi indirectly affect plant root architecture by modulating soil volatile organic compounds
(2018)
The plant-growth modulating effect of microbial volatile organic compounds (VOCs) has been demonstrated repeatedly. This has most often been performed by exposing plants to VOC released by microbes grown on nutrient rich media. Here, we used soil instead to grow fungi of the Fusarium genus and investigate how VOCs emitted by this system influenced the development of Arabidopsis plants. The volatile profiles of Fusarium strains grown in soil and malt extract were also compared. Our results demonstrate that distinct volatile signatures can be attributed to different Fusarium genetic clades but also highlight a major influence of the growth medium on volatile emission. Furthermore, all soil-grown Fusarium isolates increased primary root length in Arabidopsis by decreasing VOC concentrations in soil. This result represents a major paradigm shift in plant-microbe interactions since growth modulating effects have been attributed so far to the emission and not the consumption of volatile signals.
Tapping the full potential? Jumping performance of volleyball athletes in game-like situations
(2018)
Background: One key issue in elite interactive team sports is the simultaneous execution of motor actions (e.g., dribbling a ball) and perceptual-cognitive tasks (e.g., visually scanning the environment for action choices). In volleyball, one typical situation is to prepare and execute maximal block jumps after multiple-options decision-making and concurrent visual tracking of the ongoing game dynamics to find an optimal blocking location. Based on resource-related dual- and multi-tasking theories simultaneous execution of visual-cognitive and motor tasks may interfere with each other. Therefore, the aim of this study was to investigate whether volleyball-specific perceptual-cognitive demands (i.e., divided attention, decision making) affect blocking performance (i.e., jumping performance and length of the first step after the ready-block-position) compared to relatively isolated jumping performance.
Methods: Twenty-two elite volleyball players (1st – 3rd German league) performed block jumps in front of a net construction in a single-task condition (ST) and in two perceptual (-cognitive) dual-task conditions including a dual-task low (DT_L; presenting a picture of an opponent attack on a screen) and a dual-task high condition (DT_H; presenting videos of an offensive volleyball set play with a two-alternative choice).
Results: The results of repeated-measures ANOVAs showed a significant effect of conditions on jumping performance [F(2,42) = 33.64, p < 0.001, ηp2 = 0.62] and on the length of the first step after the ready-block-position [F(2,42) = 7.90, p = 0.001, ηp2 = 0.27). Post hoc comparisons showed that jumping performance in DT_H (p < 0.001) and DT_L (p < 0.001) was significantly lower than in ST. Also, length of the first step after the ready-block-position in DT_H (p = 0.005) and DT_L (p = 0.028) was significantly shorter than in ST.
Conclusion: Our findings suggest that blocking performance (i.e., jumping height, length of the first step) decreases in elite volleyball players when a perceptual (-cognitive) load is added. Based on the theory of Wickens (2002), this suggests a resource overlap between visual-processing demands for motor performance and for tracking the dynamics of the game. Interference with the consequence of dual-task related performance costs can therefore also be found in elite athletes in their specific motor expert domain.
Die Germanistikabteilung der Philologischen Fakultät in Kronstadt/Braşov veranstaltete in Zusammenarbeit mit der Gesellschaft der Germanisten Rumäniens [GGR] (Zweigstelle Kronstadt) und mit dem Generalkonsulat der Bundesrepublik Deutschland in Hermannstadt zwischen dem 30. März und 01. April 2017 ihre XX. Internationale Tagung zum Thema Luthers Reformation und deren Wirkung auf Sprache, Literatur und Kultur.
Die Kulturabteilung der Deutschen Botschaft Ankara, das DAAD-Informationszentrum Ankara und die Hacettepe Universität boten im Wintersemester 2016 für interessierte Masterstudierende und Doktoranden ein Workshop-Seminar zu transkulturellen Konzepten von Zeit und Raum in den Werken Ilija Trojanows an. Konzepte von Fremdheit, Migration, Transkulturalität sowie Raum und Zeit standen besonders im Fokus der Veranstaltung. In seinen Werken wirft Trojanow den Blick auf die Ausbildung interkultureller Identitäten und die damit einhergehenden Dimensionen von Fremdheit, Ablehnung und Identitäts- bzw. Zugehörigkeitsdiffusionen. Die Entfremdung von der eigenen Kultur und den damit verbundenen Perspektivwechsel thematisiert Trojanow unter anderem in seinem Werk Der Weltensammler.
In diesem Seminar stand jedoch nicht nur der Roman Der Weltensammler im Vordergrund, sondern unterschiedlichste Literatur Trojanows. Angeleitet wurden die Nachwuchswissenschaftler über zwei Präsenzseminare zum Thema Kulturanalyse und Anwendung von Methoden in der Literaturwissenschaft. Der Mehrwert des Workshop-Seminars bestand darin, dass die Studierenden Fragen aus den Werken anhand von Hypothesen direkt an den Autor stellen konnten. Um diese auch anderen Wissenschaftlern nicht vorzuenthalten, entschied man den Workshop aufzunehmen und im Anschluss zu transkribieren. Dieses Transkript bietet eine Stellungnahme über die Literatur und Philosophie Ilija Trojanows an und trägt gleichzeitig zum Textverständnis seiner Werke bei.
Folgende Werke Trojanows wurden für den Workshop ausgewählt:
Meine Olympiade: Ein Amateur, vier Jahre, 80 Disziplinen
Der Weltensammler
Der überflüssige Mensch
Macht und Widerstand
Zu den heiligen Quellen des Islam: Als Pilger nach Mekka und Medina
Die Versuchungen der Fremde: Unterwegs in Arabien, Indien und Afrika
Döner in Walhalla oder welche Spuren hinterlässt der Gast, der keiner mehr ist.
Die Studierenden, die sich eingehend mit der Literatur in Vorlauf-Präsenzseminaren beschäftigt hatten, entwarfen (kontroverse) Hypthesen, die sie Herrn Trojanow im Workshop vortrugen. Folgende Transkription wiederspiegelt einen Abriss über die Literatur Trojanows und zeigt gleichzeitig Antworten, die zum Teil auch aus einem sehr philosophischen Terminus entspringen.
Üniversiteler bilginin üretildiği yerlerdir. Bu bilgiler paylaşıldıkça anlam kazanırlar. Küresel dünyada üniversitelerden beklenen, bu bilgi paylaşımının yoğun olmasıdır. Yabancı dil bilmek bu aşamada oldukça önemlidir. Akademisyenlerin bu bilgi ağına katılım etkinliği, yabancı dili sözlü ve yazılı etkin kullanabilmesine bağlıdır. Bu çalışmanın amacı, öğretim üyelerinin yabancı dil seviyelerinin demografik değişkenlere göre ölçülmesi ve yabancı dil kullanım amaçlarının betimlenmesidir. Çalışmaya 2015 yılında Trakya Üniversitesi'nde çalışan 269 öğretim üyesi katkı sağlamıştır. Öğretim üyelerinin yabancı dil seviyeleri 'Diller için Avrupa Ortak Öneriler Çerçevesi - Ortak Öneri Düzeyleri Genel Basamaklar Kümesi - A1, A2, B1, B2, C1 ve C2' aracılığı ile ölçülmüştür. Yabancı dil kullanım amaçları ise güvenilirlik oranı % 95 olan bir ölçme aracı ile ölçülmüştür. Betimsel bir yaklaşımla yürütülen çalışmada veriler yüzdelik olarak hesaplanmıştır. Verilerin analizi çalışmaya katılan öğretim üyelerinin yaklaşık üçte birinin B1 (%30,1) ve B2 (%30,1) seviyelerinde olduğunu göstermiştir. Ayrıca yabancı dili kullanma amaçları (akademik, eğitim-öğretim ve kişisel) arasında alımlamaya ve üretime yönelik becerilerde farklılıklar tespit edilmiştir.
Das Ziel dieser Arbeit war es herauszufinden, welche Angstgefühle die DaF-Lernenden, die die deutsche Sprache innerhalb und außerhalb des deutschsprachigen Raums lernen, in Gesprächssituationen erleben. In diesem Zusammenhang wurden zwei verschiedene Probandengruppen ausgewählt und Online-Befragungen erstellt, um genauer zu untersuchen, ob es zwischen diesen Gruppen signifikante Unterschiede gibt. Die Ergebnisse, die aus der Datenauswertung erfolgen, sind für beide Lernergruppen verschieden. Nach den untersuchten Sprechtendenzen verhält sich die Gruppe aus der Türkei als eine meist affektiv eingestellte Gruppe, die beim Sprechen zurückhaltend handelt. Dagegen zeigt die Gruppe aus Deutschland tendenziell weniger Zurückhaltung gegenüber dem Sprechen in Bezug auf die emotionalen bzw. kognitionalen Einstellungen. In Bezug auf unterrichtsbezogene Sprechangst ist zu bemerken, dass die meisten Lernenden von beiden Gruppen häufig die gleiche Meinung vertreten.
Die Sprechfertigkeit ist ein Phänomen, das in fremdsprachlichen Lehr- und Lernprozessen sowohl al Mittel (Vermittlungssprache des Lehrenden) als auch als Zielfertigkeit (die es zu erreichen gilt) an Bedeutung gewinnt. Die Sprechfertigkeit, die zu den sprachlichen Fertigkeiten gehört, ist eine schwer zu entwickelnde Fähigkeit, deren Förderung im Unterricht psychologische und kognitive Mühe erfordert. In dieser Arbeit wird betont, dass es möglich ist, die Sprechfertigkeit im universitären Kontext im Rahmen der Deutschlehrerausbildung "so natürlich wie möglich, so künstlich wie nötig!" zu entwickeln; dies berücksichtigend wurde mit Beispielen erwähnt, dass das Rollenspiel und die Dramatisierungstechniken auf die Förderung der Sprechfertigkeit positiv einwirken. Diese Techniken tragen besonders dazu bei, dass der angehende Deutschlehrer einerseits seine eigene Sprechfertigkeit erweitert und andererseits methodisch-didaktische Vorbildimpulse bekommt, die er in seiner beruflichen Laufbahn als Lehrtechnik effektiv anwenden kann.
Im Jahre 1864 haben die Türken angefangen, die deutsche Sprache in den Schulen zu erteilen, nach der Ausrufung der Republik Türkei in 1923 wurde Deutsch als Fremdsprache außerhalb von Ankara, Istanbul und Izmir auch in den Provinzstädten Kastamonu und Sivas als Fachunterricht eingeführt. In der Universität Istanbul wurde im Jahre 1933 durch Mitglieder des Lehrkörpers Einwanderer aus Deutschland die Abteilung für Deutsche Sprache und Literatur an der Philosophischen Fakultät eröffnet. Die vielfältigen Beziehungen zwischen Deutschland und der Türkei sind von großer Bedeutung und haben Einfluss auf die Entwicklung des Deutschen als Fremdsprache in den Lehrplänen. Seit dem Studienjahr 2001-2002 nimmt das Deutsche als zweites Pflichtfach in den Gymnasien seinen Platz ein. Der Fernunterricht geht seit 1728 kontinuierlich weiter und die Bürger in den Entwicklungsländern profitieren von den Vorteilen des Fernunterrichts. in der Geschichte geht der Fernunterricht in der Türkei zurück bis 1927. In diesem Artikel werden die Möglichkeiten für das Lernen des Deutschen als Fremdsprache durch Fernunterricht erklärt.
Bu çalışmada, tarih boyunca yapılmış çeviriler arasından, tarihin seyrine yön verenler içinde bulunan Septuaginta adlı Tevrat çevirisi ve Reşid taşının çevirisi irdelenmektedir. Çalışmanın amacı, çevirinin her zaman sadece işlev odaklı bir uygulamadan ibaret olmadığını; bilakis sosyoloji, siyaset, ekonomi, din gibi alanlarla etkileşim içerisinde bulunan ve insanlık tarihini belirleyebilecek ölçüde önemli bir etkinlik olabileceğini belirginleştirmektir. Çalışmada, ilgili çevirilerin tarihi olgular üzerindeki etkileri ortaya konmaktadır. Çalışma kapsamında irdelenen her bir çeviri etkinliği, ortaya çıkış nedenleri ve - özellikle de tarih akışının seyrini değiştirecek - etkileri bakımından ele alınıp yorumlanmaktadır.
Ardıl çeviride not alma eğitimi konusuna ilişkin Türkçe kaynakların oldukça sınırlı olmasıyla birlikte, not alma, özellikle ardıl çeviri eğitiminde üzerinde durulması gereken önemli bir konudur. Çevirmen adayları büyük oranda, duyduğu her şeyi not alma ile anladığını not alma arasındaki ayrımı algılayacak duyarlılığa henüz sahip olmamaktadırlar. Sözlü çeviride not almanın ilkelerine ilişkin, yabancı kaynaklarda birbirinden farklı çok sayıda görüş olmasına rağmen, çıkarsama yoluyla bazı temel ilkeler belirlemek, özellikle sözlü çeviri eğitimi açısından fayda sağlayacaktır. Çalışmanın amacı, sözlü çeviride not almanın önemini irdelemenin ve söz konusu temel ilkeleri somutlaştırmanın yanı sıra, sözlü çeviri eğitiminde not alma duyarlılığını geliştirici bir açılım sunmakta belirginleşmektedir. Bu çalışma kapsamında önerilen alıştırma, öğrencilerde not alma duyarlılığının ve bilincinin gelişmesine katkı sağlayacak nitelikte olup, duyduğunu anlama, ifade gücü, belleği güçlendirme, bilgi donanımı ve genel kültür konularına da didaktik anlamda önemli ölçüde katkılar sağlayacak nitelikte bir alıştırmadır.
The aim of this article is to compare migration as an intercultural confrontation and translation as a phenomenon creating a "Third Space" for cultural negotiation. In this frame it analyses what role interculturality plays in both areas and how these areas mutually reshape the other.
The study deals with how the deconstructive approaches that have triggered a new understanding in the field influence translation. In this context, the concept of interculturality brought both by translation and migration, should not be considered as a medium for harmonization and assimilation, but as a means of respect to the foreign that challenges the asymmetries and dominance between the powers. In this sense, the study will demonstrate how intercultural migration and translation enabling constructive and productive interaction can function as a dynamic potential for cultures.
Since translation and migration are two major restorative factors for intercultural communication, they create the mobility of people so of cultures which results in a reframing of the obsolete traditional perception of culture that relies on an isolated and homogenous culture model. This communication enables not only a new understanding of the other and a convergence of the cultures involved, but it also promotes a realisation of the self and its borders
Although students make a great effort to learn a foreign language, it is an undeniable fact that they have some difficulties of understanding during communication. One of the prominent reasons of this situation is their having lack of vocabulary rather than grammar knowledge. This situation also effects the motivation of students in the process of learning negatively. Especially, words that have morphological similarities, but semantically different ones cause a problem in the process of learning, which can not be overcome without getting help professionally. The morphological similarities of the words lead students fail to understand different meanings of these kinds of words. For this reason, the purpose of this study is to investigate the words which cause difficulties because of the morphological similarities for the students to learn. As the study handles the subject in this concrete perspective, it contributes to the teachers having problems in teaching aforementioned difficult words.
Atherosclerosis and its sequelae, such as myocardial infarction and stroke, are the leading cause of death worldwide. Vascular endothelial cells (EC) play a critical role in vascular homeostasis and disease. Atherosclerosis as well as its independent risk factors including diabetes, obesity, and aging, are hallmarked by endothelial activation and dysfunction. Metabolic pathways have emerged as key regulators of many EC functions, including angiogenesis, inflammation, and barrier function, processes which are deregulated during atherogenesis. In this review, we highlight the role of glucose, fatty acid, and amino acid metabolism in EC functions during physiological and pathological states, specifically atherosclerosis, diabetes, obesity and aging.
The present study evaluated the tissue response toward a resorbable collagen membrane derived from bovine achilles tendon (test group) in comparison to physiological wound healing (control group). After subcutaneous implantation in Wistar rats over 30 days, histochemical and immunohistochemical methods elucidated the cellular inflammatory response, vascularization pattern, membrane protein and cell absorbance capacity. After 30 days, the test-group induced two different inflammatory patterns. On the membrane surface, multinucleated giant cells (MNGCs) were formed after the accumulation of CD-68-positive cells (macrophages), whereas only mononuclear cells (MNCs) were found within the membrane central region. Peri-implant vascularization was significantly enhanced after the formation of MNGCs. No vessels were found within the central region of the membrane. Physiological wound healing revealed no MNGCs at any time point. These dynamic changes in the cellular reaction and vascularization within the test-group are related typical indications of a foreign body reaction. Due to the membrane-specific porosity, mononuclear cells migrated into the central region, and the membrane maintained its integrity over 30 days by showing no breakdown or disintegration. The ex vivo investigation analyzed the interaction between the membrane and a blood concentrate system, liquid platelet-rich fibrin (liquid PRF), derived from human peripheral blood and consisting of platelets, leukocytes and fibrin. PRF penetrated the membrane after just 15 min. The data question the role of biomaterial-induced MNGCs as a pathological reaction and whether this is acceptable to trigger vascularization or should be considered as an adverse reaction. Therefore, further pre-clinical and clinical studies are needed to identify the types of MNGCs that are induced by clinically approved biomaterials.
Many cellular processes are regulated via pH, and maintaining the pH of different organelles is crucial for cell survival. A pH-sensitive GFP variant, the so-called pHluorin, has proven to be a valuable tool to study the pH of the cytosol, mitochondria and other organelles in vivo. We found that the fluorescence intensity of Endoplasmic Reticulum (ER)-targeted pHluorin in the yeast Saccharomyces cerevisiae was very low and barely showed pH sensitivity, probably due to misfolding in the oxidative environment of the ER. We therefore developed a superfolder variant of pHluorin which enabled us to monitor pH changes in the ER and the cytosol of S. cerevisiae in vivo. The superfolder pHluorin variant is likely to be functional in cells of different organisms as well as in additional compartments that originate from the secretory pathway like the Golgi apparatus and pre-vacuolar compartments, and therefore has a broad range of possible future applications.
Background: Treatment complexity rises in line with the number of drugs, single doses, and administration methods, thereby threatening patient adherence. Patients with multimorbidity often need flexible, individualised treatment regimens, but alterations during the course of treatment may further increase complexity. The objective of our study was to explore medication changes in older patients with multimorbidity and polypharmacy in general practice.
Methods: We retrospectively analysed data from the cluster-randomised PRIMUM trial (PRIoritisation of MUltimedication in Multimorbidity) conducted in 72 general practices. We developed an algorithm for active pharmaceutical ingredients (API), strength, dosage, and administration method to assess changes in physician-reported medication data during two intervals (baseline to six-months: ∆1; six- to nine-months: ∆2), analysed them descriptively at prescription and patient levels, and checked for intervention effects.
Results: Of 502 patients (median age 72 years, 52% female), 464 completed the study. Changes occurred in 98.6% of patients (changes were 19% more likely in the intervention group): API changes during ∆1 and ∆2 occurred in 414 (82.5%) and 338 (67.3%) of patients, dosage alterations in 372 (74.1%) and 296 (59.2%), and changes in API strength in 158 (31.5%) and 138 (27.5%) respectively. Administration method changed in 79 (16%) of patients in both ∆1 and ∆2. Simvastatin, metformin and aspirin were most frequently subject to alterations.
Conclusion: Medication regimens in older patients with multimorbidity and polypharmacy changed frequently. These are mostly due to discontinuations and dosage alterations, followed by additions and restarts. These findings cast doubt on the effectiveness of cross-sectional assessments of medication and support longitudinal assessments where possible.
Trial registration: 1. Prospective registration: Trial registration number: NCT01171339; Name of registry: ClinicalTrials.gov; Date of registration: July 27, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
2. Peer reviewed trial registration: Trial registration number: ISRCTN99526053; Name of registry: Controlled Trials; Date of registration: August 31, 2010; Date of enrolment of the first participant to the trial: August 12, 2010.
In the publication of this article, there are reference errors in four positions the respective references are missing since reference Fischer was omitted. In addition for reference Egli et al. the in text citation only appeared at the end of the paragraph, but not following important statements. This has now been included in this correction. ...
Objective: Classifications of posture deviations are only possible compared with standard values. However, standard values have been published for healthy male adults but not for female adults.
Design: Observational study.
Setting: Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe-University Frankfurt/Main.
Participants: 106 healthy female volunteers (21–30 years old; 25.1±2.7 years) were included. Their body weight ranged from 46 to 106 kg (60.3±7.9 kg), the heights from 1.53 to 1.82 m (1.69±0.06 m) and the body mass index from 16.9 kg/m² to 37.6 kg/m² (21.1±2.6 kg/m²).
Outcome measures: A three-dimensional back scan was performed to measure the upper back posture in habitual standing. The tolerance ranges and CI were calculated. Group differences were tested by the Wilcoxon Mann-Whitney U test.
Results: In normal posture, the spinal column was marginally twisted to the left, and the vertebrae were marginally rotated to the right. The kyphosis angle is larger than the lumbar angle. Consequently, a more kyphotic posture is observed in the sagittal plane. The habitual posture is slightly scoliotic with a rotational component (scapular depression right, right scapula marginally more dorsally, high state of pelvic right, iliac right further rotated anteriorly).
Conclusions: Healthy young women have an almost ideally balanced posture with minimal ventral body inclination and a marginal scoliotic deviation. Compared with young males, women show only marginal differences in the upper body posture. These values allow a comparison to other studies, both for control and patient data, and may serve as guideline in both clinical practice and scientific studies.
Self-organized robots may develop attracting states within the sensorimotor loop, that is within the phase space of neural activity, body and environmental variables. Fixpoints, limit cycles and chaotic attractors correspond in this setting to a non-moving robot, to directed, and to irregular locomotion respectively. Short higher-order control commands may hence be used to kick the system from one self-organized attractor robustly into the basin of attraction of a different attractor, a concept termed here as kick control. The individual sensorimotor states serve in this context as highly compliant motor primitives. We study different implementations of kick control for the case of simulated and real-world wheeled robots, for which the dynamics of the distinct wheels is generated independently by local feedback loops. The feedback loops are mediated by rate-encoding neurons disposing exclusively of propriosensoric inputs in terms of projections of the actual rotational angle of the wheel. The changes of the neural activity are then transmitted into a rotational motion by a simulated transmission rod akin to the transmission rods used for steam locomotives. We find that the self-organized attractor landscape may be morphed both by higher-level control signals, in the spirit of kick control, and by interacting with the environment. Bumping against a wall destroys the limit cycle corresponding to forward motion, with the consequence that the dynamical variables are then attracted in phase space by the limit cycle corresponding to backward moving. The robot, which does not dispose of any distance or contact sensors, hence reverses direction autonomously.
Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).
Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.
Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.
Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.
Cultural psychology assumes that the ecocultural conditions of a particular setting shape children’s pathways, resulting in multiple adaptive solutions to universal developmental tasks. While the adaptivity of attachment and children’s psychosocial development during the early years has been thoroughly investigated, attachment research during middle childhood continues to reflect Western ideals of family. Adhering to ideas of monotropy, most studies only focus on parental attachment figures. However, this restricted empirical perspective does not only result in a Eurocentric bias, it also neglects theoretical reflections on the growing complexity of attachment during middle childhood, thus only considering a limited selection of all individuals contributing to the children’s feeling of security, even in Western settings. To investigate the variability and adaptivity of attachment during middle childhood, this study assessed children’s attachment figures in two extreme settings of development, introducing an exhaustive network perspective on attachment during this developmental stage. Children of the Cameroonian Nseh (N = 11) and German children from Bad Nauheim (N = 11) identified and differentiated all individuals contributing to their attachment need in an exploratory and transdisciplinary approach. The socio-structural composition of children’s attachment networks follows the context-specific systems of care and concepts of interconnectedness and the ecological features of each setting, resulting in marked differences between both contexts. The functional composition, however, reflects children’s preoccupation with similar developmental challenges across settings. Same-aged peers contribute to the children’s feeling of safety in both settings, thereby deviating from previous reflections on their subordinate relevance during middle childhood. Overall, these results support the adaptiveness of children’s attachment patterns while also demonstrating universal trends across contexts. They highlight the collective nature of attachment during middle childhood that exceeds the impact of individual dyads. Thus, broad and context-sensitive research strategies become a necessary addition to attachment research in order to generate an exhaustive understanding for children’s development across cultural contexts.
Our ability to select relevant information from the environment is limited by the resolution of attention – i.e., the minimum size of the region that can be selected. Neural mechanisms that underlie this limit and its development are not yet understood. Functional magnetic resonance imaging (fMRI) was performed during an object tracking task in 7- and 11-year-old children, and in young adults. Object tracking activated canonical fronto-parietal attention systems and motion-sensitive area MT in children as young as 7 years. Object tracking performance improved with age, together with stronger recruitment of parietal attention areas and a shift from low-level to higher-level visual areas. Increasing the required resolution of spatial attention – which was implemented by varying the distance between target and distractors in the object tracking task – led to activation increases in fronto-insular cortex, medial frontal cortex including anterior cingulate cortex (ACC) and supplementary motor area, superior colliculi, and thalamus. This core circuitry for attentional precision was recruited by all age groups, but ACC showed an age-related activation reduction. Our results suggest that age-related improvements in selective visual attention and in the resolution of attention are characterized by an increased use of more functionally specialized brain regions during the course of development.
The social construction of technological stasis : the stagnating data structure in OpenStreetMap
(2018)
The article aims for examining the ‘technological stasis’ of the data structure in OpenStreetMap – the successful global collaborative geodata project devoted to ‘create and distribute free geographic data for the world’. Digital structures are strongly influenced by continuing stagnation. This technological stasis – the lack of change in technology – influences data in various ways, as demonstrated by the intensive discussion of the issue by computer scientists and software engineers. However, existing research describing stagnating software is often technic centred and fuzzy, while critical research is barely considering issues of technological stasis in the digital context at all. Therefore, this paper aims for enriching this body of knowledge in order to shed light on aging data structures. I reframe technological stasis with a social-constructivist perspective – using the approach of Social Construction of Technology – especially with the concept of technological frames. Based on the case example of OpenStreetMap, my findings suggest that the data structure – and its stasis – is the outcome of competing understandings and perspectives, shaped by power asymmetries. Although the data structure did not significantly change for more than 10 years, I demonstrate that this is not because of a lack of motivation, nor technological difficulties of carrying out such changes. The technological stasis is rather rooted in the dominant position of few project members who are able to change the software design; it is their perception of the project that defines how data should be stored and what features are dispensable.
Adjektivbildungen mit unterschiedlichen Suffixen sind im Deutschen häufig, aber der differenzierte Gebrauch entspricht gewollten Bedeutungsunterschieden. Diese Bildungen scheinen keiner durchgehenden Systematik entsprechen zu wollen, sondern gehorchen in ihrer möglichen Verwendung der Konvention, der herrschenden Übereinkunft über den Alltagssprachgebrauch. Diesen muss man jeweils am Einzelbeispiel erlernen. Das Eindringen in das Verständnis solcher Möglichkeiten verfeinert das Sprachgefühl in erheblichem Maß. Solches kann man auch in den Unterricht einbringen.
Modern Kuramların Postmodern Yansımaları: Okur Odaklı Edebiyat Kuramlarında Okurun Konumlandırılışı
(2017)
20. yüzyılın ikinci yarısından itibaren edebiyat alanında önemli bir paradigma değişikliğinin gerçekleştiği söylenebilir. Bu değişiklik genel olarak edebiyat kuram ve eleştirilerinin o güne kadar ihmal ettiği ancak en başından itibaren edebiyatın en önemli parçası olan okurun yeni bir yönüyle keşfedilmesi ve yeniden tanımlanmasıyla gerçekleşir. Yazar ve onun yazdığı metin karşısında o güne kadar edilgen bir rol biçilen okur, dönemin koşullarının da elverişli olması nedeniyle aşama aşama etken bir role büründürülür. 1970'li yıllardan itibaren ise okurun bu özelliğini ele alan bir dizi yeni bakış açısı ve yaklaşım ortaya çıkar. Özellikle Almanya, Amerika ve Fransa'da ortaya çıkan bu yaklaşımların her birisi beslendikleri felsefi geleneğin etkisi altında farklı bir okur modeli geliştirirler. Bu çalışmada bu farklı okur modellerinden üç tanesi incelenerek okur kavramı ile neyi veya kimi kastettikleri üzerinde durulmuştur. Bu üç farklı yaklaşımın ele alınmasındaki amaç ise, günümüzde edebiyat metnini anlamlandırmada etken bir rol üstlenen okuru tanımlamak üzere kullanılan "postmodern okur" modeline katkılarının olupc olmadığını sorgulamaktır.
Die vorliegende Untersuchung beabsichtigt die Schönheitsauffassung in der deutschen und türkischen Erzählwelt in ihrer Bedeutung, Funktionalität und kulturellen Einbettung herauszuarbeiten. Ausgehend von den Märchen der Brüder Grimm (Erstausgabe von 1812 und 1815) und den türkischen Märchen von Ignácz Kúnos (Erstfassung,1887) werden die Begriffe "schön", "Schönheit" und "Ästhetik" analysiert und zur Diskussion gestellt. Mittels einer Korpusanalyse werden so die Märchentexte einer hermeneutisch-analytischen, mythologischen und kulturtheoretisch-kritischen Betrachtung unterzogen. Ziel dabei sind die Maßstäbe der Schönheit zu hinterfragen. Was wird in der Märchenwelt als "schön" empfunden? Worin liegt die Grenze vom Schönen zum Hässlichen? Hier ist auch zu fragen, inwieweit das kulturelle Umfeld die Auffassung zum Schönen beeinträchtigt
Ingeborg Rapoports Autobiografie geht über eine Autofiktion hinaus und greift auf ihre interkulturellen Erfahrungen auf. Ihr autobiografisches Schreiben konzentriert sich insofern auf ihre unterschiedlichen Erfahrungen in den verschiedenen Heimaten (Kamerun, USA und Deutschland). Der vorliegende Beitrag untersucht Dimensionen ihres interkulturellen Lebenslaufs. Ausgegangen wird davon, dass die postmoderne Autobiographie zum Medium der Interkulturalität geworden ist.
Rapoport versteht sich besonders als Zeugin ihres Jahrhunderts und stellt die Kolonisierung in ihrer Heimat Kamerun, den deutschen Nazismus sowie den Holocaust, die unkritische Zusammenarbeit zwischen Nord und Süd als die einen fruchtbaren interkulturellen Austausch hindernden Faktoren dar.
Exemplarisch wird an Rapoports Äußerungen nachgewiesen, inwiefern Interkulturalität und Engagement Hand in Hand gehen. In ihrem interkulturellen Engagement tritt Rapoport auf als Antikolonialistin, Nazismus- und Holocaustkritikerin und besonders aber auch als eine den Frieden suchende Autorin, deren Denkweise in die Nähe des Levinasschen Humanismus gerückt werden dürfte.
Scharlatane waren für die Gelehrtendiskurse der Frühen Neuzeit von kaum zu überschätzender Bedeutung, da sich anhand ihres Negativbeispiels Verhaltensideale formulieren ließen, die für die Wissenschaft maßgeblich waren. Das Interesse an dieser Figur reichte auch in die Literatur hinein, wo sie in vielfältiger Weise aufgegriffen wurde und um 1800 verstärkt in Erscheinung trat. Christoph Martin Wieland war einer der Autoren, die sich besonders intensiv mit ihr befassten. In seinem Roman Geschichte der Abderiten (1773-1779) inszeniert er den geistigen Gegensatz, der zwischen dem Protagonisten Demokrit, einem beispielhaften Gelehrten, und seinen Mitbürgern, den törichten Abderiten, besteht. Die These des vorliegenden Beitrags lautet, dass Wieland damit auf eine poetische Reflexion von Wissen abzielt, wobei er mit Hilfe des Scharlatanmotivs die wissenschaftlichen Ausschlussmechanismen seiner Zeit ironisiert. Mithin sind es die Bedingungen der Produktion von Wissen, die im Text aufs Korn genommen werden. Dabei spielt Wieland die komischen Konflikte durch, die auftreten können, wenn das der Aufklärung nahestehende Wissenschaftsethos eines Demokrit auf den Eigendünkel einer unaufgeklärten Gesellschaft trifft.
Anlässlich der Gedenkfeier 'Zum 100. Geburtstag des Dichters Oğuz Tansel und die türkische Märchenwelt' fand an der Middle East Technical University (Technische Universität des Nahen Osten; kurz: METU/ODTÜ) in Ankara eine internationale Tagung statt. Im Rahmen einer zwei tägigen wissenschaftlichen Veranstaltung vom 20. bis 21. Oktober 2016 wurde der renommierte Volkskundler und Dichter Oğuz Tansel im Kultur- und Kongresszentrum von METU/ODTÜ feierlich geehrt. Organisiert wurde die Tagung von der Abteilung für 'Türkische Sprache' (Türk Dili Bölümü), METU/ODTÜ und dem Forschungszentrum für Kinder- und Jugendliteratur der Universität Ankara (kurz: ÇOGEM).
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, besonders nach der politischen Umgestaltung des Landes sehr stark gestiegen. Der Fachbereich Germanistik der West-Universität Temeswar veranstaltete in Zusammenarbeit mit der Österreich-Bibliothek Temeswar, der Gesellschaft der Germanisten Rumäniens (Zweigstelle Temeswar) und dem Deutschem Kulturzentrum Temeswar zwischen dem 20.-22. Oktober 2016 ihre internationale Tagung zum Thema Germanistik zwischen Regionalität und Internationalität: 60 Jahre Temeswarer Germanistik.
Türkiye ile Almanya arasında siyasi, ekonomik, bilimsel, ticari, kültürel ve daha birçok alanda yoğun bir işbirliği söz konusudur. Ayrıca Almanya’da yaklaşık üç milyon Türkiye vatandaşı yaşamakta ve Türkiye'ye uzun yıllardır en fazla yabancı turist Almanya'dan gelmektedir. Bütün bu nedenlerden dolayı Almanca konuşabilmek Türkiye'de farklı sektörlerden birçok iş kolunda çalışanlarda aranan bir nitelik haline gelmiştir. Turizm bu sektörlerin başında gelmektedir. Turizm çalışanlarının ihtiyaçları doğrultusunda kurslarda, ilgili fakülte ve yüksekokullarda mesleki Almanca dersleri verilmektedir. Mesleki Almanca öğretimi için bilinen dil öğretim yöntemleri kullanılmakla birlikte, ilgili meslek kolunun gerektirdiği dilsel beceriler göz ününde bulundurularak farklı yöntem ve tekniklerden de yararlanılmaktadır. Bu çalışmada turizm mesleki dili tanımlanıp, örneklerle açıklanmış ve yabancı dil öğretim yöntemlerinin özellikleri açıklanarak, turizm için mesleki Almanca bilgi ve becerilerini kazandırmadaki yeterliliği üzerine bir tartışma yürütülmüştür. Çalışmada herhangi bir örneklem grubu üzerinde deney veya gözlem yapılmaksızın, konuyla ilgili yapılan çalışmalar, öğretmen ve öğrenci görüşleri dikkate alınmıştır.
Parkinson’s disease (PD) is characterized by distinct motor and non-motor symptoms. Sleep disorders are the most frequent and challenging non-motor symptoms in PD patients, and there is growing evidence that they are a consequence of disruptions within the circadian system. PD is characterized by a progressive degeneration of the dorsal vagal nucleus and midbrain dopaminergic neurons together with an imbalance of many other neurotransmitters. Mutations in α-synuclein (SNCA), a protein modulating SNARE complex-dependent neurotransmission, trigger dominantly inherited PD variants and sporadic cases of PD. The A53T SNCA missense mutation is associated with an autosomal dominant early-onset familial PD. To test whether this missense mutation affects the circadian system, we analyzed the spontaneous locomotor behavior of non-transgenic wildtype mice and transgenic mice overexpressing mutant human A53T α-synuclein (A53T). The mice were subjected to entrained- and free-running conditions as well as to experimental jet lag. Furthermore, the vesicular glutamate transporter 2 (VGLUT2) in the suprachiasmatic nucleus (SCN) was analyzed by immunohistochemistry. Free-running circadian rhythm and, thus, circadian rhythm generation, were not affected in A53T mice. A53T mice entrained to the light–dark cycle, however, with an advanced phase angle of 2.65 ± 0.5 h before lights off. Moreover, re-entrainment after experimental jet lag was impaired in A53T mice. Finally, VGLUT2 immunoreaction was reduced in the SCN of A53T mice. These data suggest an impaired light entrainment of the circadian system in A53T mice.
Bu çalışmada öğrencilerin öğrenmiş oldukları dilbilgisel yapıyı nasıl işlevsel hale getireceği, pasif halde bulunan dilbilgisel yapının nasıl aktif hale getirileceği teorik ve deneysel bağlamda incelenmiştir. Tek tip pasif alıştırmaların yerine aktif alıştırma tiplerinden seçenek sunularak öğrencilerin bu bilgiyi, dört beceriye aktarımı mümkün kılınmaya çalışılmıştır. Çalışmada dört beceri birbirinden soyutlanmış biçimde değil bütünleştirici şekilde ele alınmıştır.
Bu çalışmada deneysel yöntemin 'kontrol gruplu öntest ve sontest deney' deseni kullanılmıştır. Hem nitel hem de nicel boyutları içeren karma bir çalışmadır. Çalışmada eylemsel ve üretimsel yöntemlerin kullanıldığı deney grubundaki öntest ve sontest puanları arasındaki başarı farkının; geleneksel yöntemin uygulandığı kontrol grubundaki başarı farkından anlamlı derecede fazla olduğu görülmüştür (F(1,48)=366,149; p<0,001). Buradan hareketle deney grubundaki öğrencilerin daha fazla ilerleme gösterdiği ve başarılı oldukları sonucuna varılmıştır.
Dilbilgisi dersinin iletişimsel yetinin geliştirilmesi için bir araç olduğu görüşü deneysel ve uygulamalı olarak araştırılmıştır. Yaratıcı, eyleme ve öğrencilerin üretimine dayalı bir dilbilgisi dersi geliştirilerek geleneksel dilbilgisi dersine alternatif ders modelleri geliştirilmiştir.
Jedes literarische Werk wird durch seinen Titel identifiziert. Buchtitel sollen das Interesse des Lesers wecken und ihn zum Lesen des Werkes anregen. Sie sind wohl meist kurz, geben dennoch einen ersten Hinweis auf den Inhalt und wirken rezeptionssteuernd. Bekannt ist, dass literarische Werke in andere Sprachen nicht selten unter einem anderen Titel oder unter verschiedenen Titeln erscheinen. Ein Beispiel dafür ist Thomas Manns Erzählung Die Betrogene (1953). Sie ist zuerst von Kâmuran Şipal fast 'wortgetreu' unter dem Titel Aldatılmış Kadın [Die Betrogene] (1999) und sodann davon abweichend von Esen Tezel unter dem neuen Titel Aldanan Kadın [wörtlich: Die Sichtäuschende] (2012) ins Türkische übersetzt worden. Im Allgemeinen wird die nichtwortgetreue Übersetzung von Buchtiteln beanstandet und als ein Problem gesehen, was nach translationswissenschaftlich funktionalistischer Auffassung einer differenzierten Betrachtung bedarf. Vorliegende Fallstudie behandelt diverse translationswissenschaftliche Aspekte und Faktoren der unterschiedlichen Betitelungen von Kâmuran Şipal und Esen Tezel und leistet damit einen Beitrag zur Problematik des Übersetzens von literarischen Titeln.
Abnormitäten oder Analogien bei Übersetzungen deutscher und türkischer Nebensatzkonstruktionen
(2016)
Jede Sprache hat ihre eigene grammatikalische Struktur und dementsprechend unterscheidet sich auch der Aufbau der Sätze. Was in der Grammatik als ein Teilsatz bezeichnet wird, ist ein Nebensatz, welcher in jeder Sprache seine eigene Struktur besitzt. Diese strukturellen Merkmale, Unterschiede und Ähnlichkeiten im Deutschen und im Türkischen werden in dieser Arbeit dargestellt und miteinander verglichen. In dieser Arbeit werden die deutschen Nebensatzarten samt den dazugehörigen Beispielen dargestellt. Nach denselben Gesichtspunkten werden auch die jeweiligen türkischen Übersetzungen wiedergegeben. Diese Aufteilung soll als Mittel zum Zweck der übersichtlicheren Darlegung der Nebensätze und zur Erklärung der Übersetzungsmöglichkeiten dienen. Es ist klar, dass eine konkrete Übersetzung mehr oder weniger angleichend bzw. mehr oder weniger verfremdend erscheint, welche auf Varietät der Zielsprache zurückzuführen ist. Die Gegenüberstellung zwischen von Grund aus unterschiedlichen Sprachen scheint in erster Linie in Bezug auf den Wortschatz (z. B. kulturspezifische Begriffe) und Redeweisen getroffen worden zu sein. Sie ist jedoch auch für den grammatikalischen Bereich relevant. Nach diesem Exkurs werden einige deutsche Märchen mit ihren türkischen Übersetzungen verglichen und analysiert
Çeviri eyleminin yüzyıllarla ifade edilen ve Milattan önceki devirlere kadar uzanan tarihine karşın çeviri etkinliğinin öğretilebilir bir olgu olarak ele alınması, bilindiği üzere yeni bir konudur. Bu öğretme işinin eğitme biçimiyle ele alınıp üniversiter eğitim modelleri ile ele alınması ise, görece çok daha yeni bir görüngüdür. Türkiye'de de son birkaç on yıldır çeviri eğitimi veren akademik birimlerin varlığı ile konu tamamı ile akademik mecraya taşınmış ve tartışılmaya başlanmıştır. Bu tartışmalar ise, akademik çeviri eğitimi yoluyla oluşturulması ve/veya geliştirilmesi amaçlanan 'çeviri edinci' kavramı üzerinden yürütülmektedir. Çeviri edinci, akademik çeviri eğitimi açısından merkezi bir konu olarak değerlendirilebilir. Çünkü 'çeviri edinci'nin nasıl tanımlandığı, verilen eğitimin içeriğini ve usulünü belirleyebilecek denli temel bir sorgulamadır. Bu çalışmada 'çeviri edinci' kavramı tanımlanmaya çalışılacak, buradan hareketle akademik çeviri eğitiminin koşulları ve çevirmenin öznitelikleri içeriklendirilmeye çalışılacaktır.
Chronic kidney disease and diabetes mellitus are associated with extensive media calcification, which leads to increased cardiovascular morbidity and mortality. Here, we investigated the role of autophagy in the pathogenesis of uremic vascular media calcification. DBA/2 mice were fed with high-phosphate diet (HPD) in order to cause vascular calcification. DBA/2 mice on standard chow diet were used as control. In parallel, autophagy and its response to rapamycin, 3-methyladenine (3-MA), and bafilomycin were studied in an in vitro model using mouse vascular smooth muscle cells (MOVAS). DBA/2 mice on HPD developed severe vascular media calcification, which is mirrored in vitro by culturing MOVAS under calcifying conditions. Both, in vitro and in vivo, autophagy significantly increased in MOVAS under calcifying conditions and in aortas of HPD mice, respectively. Histologically, autophagy was located to the aortic Tunica media, but also vascular endothelial cells, and was found to continuously increase during HPD treatment. 3-MA as well as bafilomycin blocked autophagy in MOVAS and increased calcification. Vice versa, rapamycin treatment further increased autophagy and resulted in a significant decrease of vascular calcification in vitro and in vivo. Rapamycin reduced Runx2 transcription levels in aortas and MOVAS to control levels, whereas it increased α-smooth muscle actin and Sm22α transcription in MOVAS to control levels. Furthermore, rapamycin-treated HPD mice survived significantly longer compared to HPD controls. These findings indicate that autophagy is an endogenous response of vascular smooth muscle cells (VSMC) to protect from calcification in uremia. Induction of autophagy by rapamycin protects cells and mice from uremic media calcification possibly by inhibiting osteogenic transdifferentiation of VSMC.
Rapid immune reconstitution (IR) following stem cell transplantation (SCT) is essential for a favorable outcome. The optimization of graft composition should not only enable a sufficient IR but also improve graft vs. leukemia/tumor effects, overcome infectious complications and, finally, improve patient survival. Especially in haploidentical SCT, the optimization of graft composition is controversial. Therefore, we analyzed the influence of graft manipulation on IR in 40 patients with acute leukemia in remission. We examined the cell recovery post haploidentical SCT in patients receiving a CD34+-selected or CD3/CD19-depleted graft, considering the applied conditioning regimen. We used joint model analysis for overall survival (OS) and analyzed the dynamics of age-adjusted leukocytes; lymphocytes; monocytes; CD3+, CD3+CD4+, and CD3+CD8+ T cells; natural killer (NK) cells; and B cells over the course of time after SCT. Lymphocytes, NK cells, and B cells expanded more rapidly after SCT with CD34+-selected grafts (P = 0.036, P = 0.002, and P < 0.001, respectively). Contrarily, CD3+CD4+ helper T cells recovered delayer in the CD34 selected group (P = 0.026). Furthermore, reduced intensity conditioning facilitated faster immune recovery of lymphocytes and T cells and their subsets (P < 0.001). However, the immune recovery for NK cells and B cells was comparable for patients who received reduced-intensity or full preparative regimens. Dynamics of all cell types had a significant influence on OS, which did not differ between patients receiving CD34+-selected and those receiving CD3/CD19-depleted grafts. In conclusion, cell reconstitution dynamics showed complex diversity with regard to the graft manufacturing procedure and conditioning regimen.
Background: Scientifically evaluated cognitive intervention programs are essential to meet the demands of our increasingly aging society. Currently, one of the “hottest” topics in the field is the improvement of working memory function and its potential impact on overall cognition. The present study evaluated the efficacy of WOME (WOrking MEmory), a theory-based working memory training program, in a double-blind, placebo-controlled, and randomized controlled trial (www.drks.de, DRKS00013162).
Methods: N = 60 healthy older adults were allocated to (1) the WOME intervention, (2) an active low-level intervention, or (3) a passive control group. Overall, the intervention groups practiced twelve sessions of 45 min within 4 weeks of their respective training. Transfer effects were measured via an extensive battery of neuropsychological tests and questionnaires both pre-/post-training and at a 3-month follow-up.
Results: WOME led to a significant improvement in working memory function, demonstrated on a non-trained near transfer task and on two different composite scores with moderate to large effect sizes. In addition, we found some indication of relevant impact on everyday life. The effects were short-term rather than stable, being substantially diminished at follow-up with only little evidence suggesting long-term maintenance. No transfer effects on other cognitive functions were observed.
Conclusion: WOME is an appropriate and efficient intervention specifically targeting the working memory system in healthy older adults.
Trial Registration: German Clinical Trials Register (DRKS), Identifier: DRKS00013162.
Im Rahmen dieser Studie wurden jeweils ein türkischer und deutscher Gebrauchs-und Informationstext und einige Sätze von literarischen Texten mit Hilfe der Online-Übersetzungsprogramme "google translate", "Babylon", "Almanca Sözlük" und "İngilizceturkce.gen" übersetzt und überprüft, ob, wenn man die Texte in der Zielsprache mit den Ausgangstexten vergleicht, syntaktische und semantische Fehler aufträten und welche der Online-Übersetzungsprogramme beim Übersetzen zuverlässig sind.
Die Daten haben dargelegt, das bei der Sprachkombination Deutsch-Türkisch/Türkisch-Deutsch Gebrauchstexte und Informationstexte, auch wenn sie einige syntaktische und semantische Fehler beinhalten, im Ganzen und Großen in die Zielsprache richtig transferiert werden, wobei literarische Texte einen höheren Anteil an Fehlern beinhalten. Laut der Untersuchungsergebnisse sollten die übersetzten Texte zur Sicherheit immer von jemand Fachkundigem gelesen werden, da beim Übersetzen von ganzen Sätzen bzw. Textpassagen aus der türkischen Sprache ins Deutsche und umgekehrt aus der deutschen Sprache ins Türkische der Sinn nicht immer erfasst wird.
Zur Kontrolle könnten außerdem noch übersetzte Passagen mit verschiedenen Programmen stückweise mehrmals oder in eine Drittsprache z. B. ins Englische übersetzt werden. Bei feststehenden Aussagen bzw. Ausdrücken hingegen ist ein hohes Maß an Aufmerksamkeit erforderlich.
Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from −25 ∘C to 25 ∘C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward.
An aerosol foam formulation of a once-daily, fixed-dose combination of a synthetic vitamin D3 analog/synthetic corticosteroid (calcipotriol [Cal] 50 µg/g and betamethasone dipropionate [BD] 0.5 mg/g) has recently been introduced for the topical treatment of plaque psoriasis in adults. Data from several sources – randomized controlled trials, case reports (as highlighted in this review), and real-world evidence (RWE) – underscore the considerable and rapid clinical response, effectiveness, and favorable safety and tolerability of Cal/BD aerosol foam in mild-to-moderate psoriatic patients previously treated with class 3 or 4 topical corticosteroids, in patients unsatisfied with ongoing phototherapy in combination with topical therapy and in patients with moderate-to-severe psoriasis. In addition, our case series, considered together with other RWE, highlights that Cal/BD aerosol foam is more effective and with greater levels of patient preference and acceptability than comparator preparations. Thus, Cal/BD aerosol foam offers several treatment advantages, including relief of itch, and is an appropriate first-line topical therapy for consideration in patients with psoriasis of any severity.
Damaged mitochondria are selectively eliminated by mitophagy. Parkin and PINK1, gene products mutated in familial Parkinson’s disease, play essential roles in mitophagy through ubiquitination of mitochondria. Cargo ubiquitination by E3 ubiquitin ligase Parkin is important to trigger selective autophagy. Although autophagy receptors recruit LC3-labeled autophagic membranes onto damaged mitochondria, how other essential autophagy units such as ATG9A-integrated vesicles are recruited remains unclear. Here, using mammalian cultured cells, we demonstrate that RABGEF1, the upstream factor of the endosomal Rab GTPase cascade, is recruited to damaged mitochondria via ubiquitin binding downstream of Parkin. RABGEF1 directs the downstream Rab proteins, RAB5 and RAB7A, to damaged mitochondria, whose associations are further regulated by mitochondrial Rab-GAPs. Furthermore, depletion of RAB7A inhibited ATG9A vesicle assembly and subsequent encapsulation of the mitochondria by autophagic membranes. These results strongly suggest that endosomal Rab cycles on damaged mitochondria are a crucial regulator of mitophagy through assembling ATG9A vesicles.
Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group.
Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation.
Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years.
Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.
Georg Forster took part in Captain Cook's second journey of the world (1772) with his father at the age of 17. After his return, he published his impressions and observations in a comprehensive book. The book contains not only the observations on the nature of the places they visited, but also numerous philosophical notes on the culture of the people. A closer reading of these observations shows that Forster developed a method according to which he assessed the foreign cultures. The criteria of this method enables Forster even to understand and objectively assess cannibalism in New Zealand. Forster developed this method after questioning the conditions which can have a significant effect on the origin and the development of a particular culture in a particular space. His observations on the different cultures and the comparison of them with the Western culture which brought him to the conclusion that the geographical location, in which the human being lives, has a great effect on human existence. The aim of this paper is to show how Forster perceives the foreign culture and how he deals with it.
Background: The city of Wrocław in Poland represents one of Central Europeans oldest capitals of science with numerous Nobel laureates. Due to a long history of political suppressions with Nazi Germany and Communism from 1933 until 1989, its scientific community was suppressed for more than half a century.
Methods: The present study assessed scientific activities in the field of social and neighbouring sciences using density equalizing mapping. On the basis of the NewQIS (New Quality and Quantity Indices in Science) platform and the Social Sciences Citation Index (SSCI) of the Web of Science database, a total of 1787 articles originating from Wrocław were identified between 1966 and 2017.
Results: In total, 549 research collaborations of Wrocław with 96 different countries were present (30.7%). Among the 107 research areas the highest activity was found for the field of Business and Economics with n = 272 articles (average citation rate (AVR) of 12.54), followed by Psychology (n = 252 articles, AVR = 9.06), Psychiatry (n = 205 articles, AVR = 4.74) and Public, Environmental and Occupational Health (n = 145 articles, AVR = 7.96). The highest AVR was found for Operations Research (25.36 with n = 87 articles). Density equalizing mapping procedures revealed a global pattern of social sciences research collaborations with scientists from Germany, the UK and the US as the primary cooperating partner of Wrocław. The different countries had major differences in the area of research collaborations.
Conclusions: This is the first study that depicts the global network of Wrocław scientific activities in the field of social sciences. The exorbitant increase in research activity from 2006 onwards can lead to the assumption that Wrocław social sciences encounter a fruitful future.
Franz Kafka'nın Dava'sının Melih Cevdet Anday'ın İsa'nın Güncesi adlı romanına etkisi açık olmakla birlikte, incelenen romanlar arasındaki ilişki, basit bir esinlenmenin ötesinde, eserlerin kaleme alındığı dönemlerdeki toplumsal ve hukuki sorunların özüne ilişkin benzerlikle dikkat çekmektedir. Romanların karşılaştırmalı analizi, modernitenin, toplumsal farklılıklar ve iki roman arasındaki altmış yıla rağmen, değişik kültürlerde hukuk felsefesine ilişkin benzer sorunlara yol açtığını göstermektedir. Ulus devletlerinin kurulması ve demokrasinin gelişmesiyle ortaya çıkan kriz kalıcı olmuş, dünya savaşları ve askeri darbeler arasında olağan hâle gelen olağanüstü hâl modern dönemin hukuki durumu hâline gelmiştir.
Determining the cell fate and the distribution of mesenchymal stromal/stem cells (MSCs) after transplantation are essential parts of characterizing the mechanisms of action and biosafety profile of stem cell therapy. Many recent studies have shown that MSCs migrate into injured tissues, but are only detectable at extremely low frequencies. We investigated the cell fate of MSCs after transplantation in an acute kidney injury (AKI) mouse model using in vivo bioluminescence imaging (BLI) and subsequent verification of cell migration using quantitative real-time polymerase chain reaction (qRT-PCR). The AKI was induced by a single injection of cisplatin (8 or 12 mg/kg). One day later, adipose-derived mesenchymal stromal/stem cells isolated from luciferase transgenic mice (Luc+-mASCs, 5 × 105) were intravenously transplanted. Migration kinetics of the cells was monitored using BLI on day 1, 3, and 6, and finally via quantitative real-time PCR at the endpoint on day 6. Using BLI, infused Luc+-mASCs could only be detected in the lungs, but not in the kidneys. In contrast, PCR endpoint analysis revealed that Luc-specific mRNA could be detected in injured renal tissue; compared to the control group, the induction was 2.2-fold higher for the 8 mg/kg cisplatin group (p < 0.05), respectively 6.1-fold for the 12 mg/kg cisplatin group (p < 0.001). In conclusion, our study demonstrated that Luc-based real-time PCR rather than BLI is likely to be a better tool for cell tracking after transplantation in models such as cisplatin-induced AKI.
Subduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence for contributions of oxidising slab agents to melts trapped in the sub-arc mantle. Measurements of sulfur (S) valence state in sub-arc mantle peridotites identify sulfate, both as crystalline anhydrite (CaSO4) and dissolved SO42− in spinel-hosted glass (formerly melt) inclusions. Copper-rich sulfide precipitates in the inclusions and increased Fe3+/∑Fe in spinel record a S6+–Fe2+ redox coupling during melt percolation through the sub-arc mantle. Sulfate-rich glass inclusions exhibit high U/Th, Pb/Ce, Sr/Nd and δ34S (+ 7 to + 11‰), indicating the involvement of dehydration products of serpentinised slab rocks in their parental melt sources. These observations provide a link between liberated slab components and oxidised arc magmas.
GD2-directed immunotherapies improve survival of high-risk neuroblastoma (NB) patients (pts). Treatment with chimeric anti-GD2 antibodies (Ab), such as ch14.18, can induce development of human anti-chimeric Ab (HACA). Here, we report HACA effects on ch14.18/CHO pharmacokinetics, pharmacodynamics and pain intensity in pts treated by long-term infusion (LTI) of ch14.18/CHO combined with IL-2. 124 pts received up to 5 cycles of ch14.18/CHO 10 days (d) infusion (10 mg/m2/d; d8–18) combined with s.c. IL-2 (6 × 106 IU/m2/d; d1–5, d8–12). HACA, treatment toxicity, ch14.18/CHO levels, Ab-dependent cellular- (ADCC) and complement-dependent cytotoxicity (CDC) were assessed using respective validated assays. HACA-negative pts showed a steadily decreased pain in cycle 1 (74% pts without morphine by d5 of LTI) with further decrease in subsequent cycles. Ch14.18/CHO peak concentrations of 11.26 ± 0.50 µg/mL found in cycle 1 were further elevated in subsequent cycles and resulted in robust GD2-specific CDC and ADCC. Development of HACA (21% of pts) resulted in strong reduction of ch14.18/CHO levels, abrogated CDC and ADCC. Surprisingly, no difference in pain toxicity between HACA-positive and -negative pts was found. In conclusion, ch14.18/CHO LTI combined with IL-2 results in strong activation of Ab effector functions. Importantly, HACA response abrogated CDC but did not affect pain intensity indicating CDC-independent pain induction.
Introduction: Hip fracture surgery is associated with high in-hospital and 30-day mortality rates and serious adverse patient outcomes. Evidence from randomised controlled trials regarding effectiveness of spinal versus general anaesthesia on patient-centred outcomes after hip fracture surgery is sparse.
Methods and analysis: The iHOPE study is a pragmatic national, multicentre, randomised controlled, open-label clinical trial with a two-arm parallel group design. In total, 1032 patients with hip fracture (>65 years) will be randomised in an intended 1:1 allocation ratio to receive spinal anaesthesia (n=516) or general anaesthesia (n=516). Outcome assessment will occur in a blinded manner after hospital discharge and inhospital. The primary endpoint will be assessed by telephone interview and comprises the time to the first occurring event of the binary composite outcome of all-cause mortality or new-onset serious cardiac and pulmonary complications within 30 postoperative days. In-hospital secondary endpoints, assessed via in-person interviews and medical record review, include mortality, perioperative adverse events, delirium, satisfaction, walking independently, length of hospital stay and discharge destination. Telephone interviews will be performed for long-term endpoints (all-cause mortality, independence in walking, chronic pain, ability to return home cognitive function and overall health and disability) at postoperative day 30±3, 180±45 and 365±60.
Ethics and dissemination: iHOPE has been approved by the leading Ethics Committee of the Medical Faculty of the RWTH Aachen University on 14 March 2018 (EK 022/18). Approval from all other involved local Ethical Committees was subsequently requested and obtained. Study started in April 2018 with a total recruitment period of 24 months. iHOPE will be disseminated via presentations at national and international scientific meetings or conferences and publication in peer-reviewed international scientific journals.
Trial registration number: DRKS00013644; Pre-results
Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-generation sequencing technologies to undiagnosed cohorts has been a catalyst for genetic diagnosis and gene-disease associations. We describe the clinical and molecular genetic investigations of four unrelated children who presented with neuroradiological findings and/or elevated lactate levels, highly suggestive of an underlying mitochondrial diagnosis. Next-generation sequencing identified bi-allelic variants in NDUFA6, encoding a 15 kDa LYR-motif-containing complex I subunit that forms part of the Q-module. Functional investigations using subjects’ fibroblast cell lines demonstrated complex I assembly defects, which were characterized in detail by mass-spectrometry-based complexome profiling. This confirmed a marked reduction in incorporated NDUFA6 and a concomitant reduction in other Q-module subunits, including NDUFAB1, NDUFA7, and NDUFA12. Lentiviral transduction of subjects’ fibroblasts showed normalization of complex I. These data also support supercomplex formation, whereby the ∼830 kDa complex I intermediate (consisting of the P- and Q-modules) is in complex with assembled complex III and IV holoenzymes despite lacking the N-module. Interestingly, RNA-sequencing data provided evidence that the consensus RefSeq accession number does not correspond to the predominant transcript in clinically relevant tissues, prompting revision of the NDUFA6 RefSeq transcript and highlighting not only the importance of thorough variant interpretation but also the assessment of appropriate transcripts for analysis.
Aims: The ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements.
Methods: Patients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured.
Results: Five hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal range throughout follow-up and 76.7% of patients did not require IOP-lowering therapy following treatment with the FAc implant. Sixty-nine per cent of eyes did not require additional DMO treatments. Mean VA in the overall population increased from 51.9 letters at baseline to 55.6 letters at month 12, with a significant increase of 2.9 letters at last observation. Patients with short-term cDMO experienced greater VA gains than those with long-term cDMO.
Conclusions: The results of this analysis are comparable with those of other studies, including the Fluocinolone Acetate for Macular Edema study. The study reinforces the good safety and effectiveness profile of FAc, and demonstrates the benefit of early FAc treatment.
To crack the neural code and read out the information neural spikes convey, it is essential to understand how the information is coded and how much of it is available for decoding. To this end, it is indispensable to derive from first principles a minimal set of spike features containing the complete information content of a neuron. Here we present such a complete set of coding features. We show that temporal pairwise spike correlations fully determine the information conveyed by a single spiking neuron with finite temporal memory and stationary spike statistics. We reveal that interspike interval temporal correlations, which are often neglected, can significantly change the total information. Our findings provide a conceptual link between numerous disparate observations and recommend shifting the focus of future studies from addressing firing rates to addressing pairwise spike correlation functions as the primary determinants of neural information.
Autophagy acts through TRAF3 and RELB to regulate gene expression via antagonism of SMAD proteins
(2017)
Macroautophagy can regulate cell signalling and tumorigenesis via elusive molecular mechanisms. We establish a RAS mutant cancer cell model where the autophagy gene ATG5 is dispensable in A549 cells in vitro, yet promotes tumorigenesis in mice. ATG5 represses transcriptional activation by the TGFβ-SMAD gene regulatory pathway. However, autophagy does not terminate cytosolic signal transduction by TGFβ. Instead, we use proteomics to identify selective degradation of the signalling scaffold TRAF3. TRAF3 autophagy is driven by RAS and results in activation of the NF-κB family member RELB. We show that RELB represses TGFβ target promoters independently of DNA binding at NF-κB recognition sequences, instead binding with SMAD family member(s) at SMAD-response elements. Thus, autophagy antagonises TGFβ gene expression. Finally, autophagy-deficient A549 cells regain tumorigenicity upon SMAD4 knockdown. Thus, at least in this setting, a physiologic function for autophagic regulation of gene expression is tumour growth.
Peter Weiss'ın Direnmenin Estetiği romanı tematik kurgusu içinde geçmişteki direnişleri belgeleyen sanat ve edebiyat eserlerini yeniden yorumlayan bir çizgi izlemektedir. Sosyalizmin pratiklerini içeriden eleştiren bu roman sosyalist gerçekçiliği de konu etmektedir. Bu kapsamda işçi perspektifinden yazılmış bir roman olan Klaus Neukrantz'ın Wedding Barikatları ile - sosyalist gerçekçilik çizgisinin dekadan (yozlaşmış) yazar kabul ettiği - Franz Kafka'nın Şato romanı arasında bir yakınlık ilişkisi kurmakta, Şato için 'işçi sınıfının romanı' ifadesini kullanmaktadır. Bu bağlamda Peter Weiss'ın sosyalist gerçekçiliği nasıl yorumladığı, sosyalist iktidarların sanat ve edebiyat üzerindeki denetimlerine itiraz etmesine rağmen sosyalist gerçekçilikte hangi değeri gördüğü ve Kafka’nın Şato romanına 'işçi sınıfının romanı' derken nasıl bir bağlantı kurduğu çarpıcı bir soru haline gelmektedir.
Bu makale, adı geçen iki eserin özelliklerini ve düzen karşısındaki konumlanmalarını karşılaştırmalı olarak incelemektedir; Direnmenin Estetiği'nde bu iki romanla ilgili bölümlerde, romanın genel kurgusu ve yaklaşımı dikkate alınarak değerlendirilmektedir. Bu incelemeyle, Peter Weiss'ın sosyalist gerçekçiliğe bakışındaki özgünlüğü ve bu bağlamda nasıl bir Kafka yorumu yaptığını göstermek amaçlanıyor. İncelemenin vardığı sonuç: Peter Weiss; Kafka'nın, mücadelenin hedefini gösteren sosyalist gerçekçiliğin eksik bıraktığı şeyi yaptığını, yani ezilenlerin kendi içsel yaşantılarını bulmalarını sağladığını düşünmektedir. Yine Direnmenin Estetiği'nde izlerine rastlandığı gibi, Peter Weiss hayatının önemli bir bölümünde kendini Kafka’nın dünyasında hissetmiştir. Bu da Kafka'yı Peter Weiss için önemli kılan bir başka unsurdur. Bu anlamda Direnmenin Estetiği romanı Franz Kafka, Klaus Neukrantz ve Peter Weiss'ın ortak noktalarının izini süren, üç kurgusal metnin iç içe geçtiği bir üst metin olarak görülebilir.
Die aktuellen Ereignisse in Europa und die Migrationskrise bewegen die ganze Welt. Mit diesem Thema beschäftigte sich die internationale Konferenz, die im Rahmen des europäischen Projekts "My!Europe" der Sonnenberg-Kreis der Tschechischen Republik in Zusammenarbeit mit dem Lehrstuhl für Fremdsprachen der Philosophischen Fakultät der Universität Pardubice von 7.- 8. April 2016 veranstaltete. Am akademischen Boden der ostböhmischen Universität trafen sich 130 Fachleute, Interessenten, Studenten und Schüler.
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, besonders nach der blutigen und gewaltsamen Wende, stark gestiegen. Die Germanistikabteilung der Philologischen Fakultät in Kronstadt/Braşov veranstaltete in Zusammenarbeit mit der Gesellschaft der Germanisten Rumäniens [GGR] (Zweigstelle Kronstadt) zwischen dem 07. - 09. April 2016 ihre XIX. Internationale Tagung zum Thema Konstruktionen von Männlichkeit und Weiblichkeit in der deutschen Kultur, Literatur und Sprache.
Erfahrungen mit Wikipedia.de
(2016)
Ausgehend von der unsystematischen Mitarbeit einerseits, der laufenden Beobachtung einiger mit dieser Absicht geschriebenen Artikel (zur Volksliedforschung) andererseits sollen weitgehend allgemein gültige Beobachtungen und Erfahrungen mit der deutschen Wikipedia skizziert werden. Damit soll diese für türkische Studierende äußerst wichtige Informationsquelle transparenter gemacht werden, und damit soll zu einer kreativ-kritischen Verwendung von Wikipedia angeregt werden.
Wikipedia kann im Unterricht verwendet werden, ja den richtigen Gebrauch von Wikipedia zu lernen, sollte wichtiges Unterrichtsthema sein. Wikipedia regt zur Mitarbeit an; man sollte allerdings wissen, worauf man sich einlässt.
İkinci dil öğrenme yaşına ilişkin tartışmalar sürerken, birçok gelişmiş ülkede olduğu gibi ülkemizde de anaokulundan itibaren yabancı dil öğretimi gerçekleştirilmektedir. Yabancı dil öğreniminde, görsel-işitsel araç kullanarak dile ait konuşma seslerinin ve sözcüklerin doğru telaffuzunu duymak, doğru telaffuz edebilmek ve dilin ait olduğu kültürü tanımak çok önemlidir. Erken yaşta yabancı dil öğrenimine bu açıdan yaklaşıldığında dil öğreniminde yabancı bir dile ve kültüre ait çizgi filmlerin yeri, üzerinde durulması gereken bir konu olarak karşımıza çıkmaktadır. Bu çalışmada, okul öncesi dönem çocuklarının yabancı dil öğreniminde çizgi filmlerin yeri incelenmiştir. Bu kapsamda, yabancı dil öğrenme yaşı, yabancı dil öğretim yöntemleri kuramsal açıdan ele alınmış; çizgi filmlerin yabancı dil öğrenimindeki yeri üzerinde durularak, ne tür çizgi filmlerin erken yaşta yabancı dil öğreniminde daha etkin ve yararlı olduğu ortaya konulmaya çalışılmıştır.
Der Faktor 'Sommerferien' beim Übergang von der
Vorbereitungsklasse in die Deutschlehrerausbildung
(2016)
Die Eingangssprachkenntnisse der Studierenden des Studiengangs 'Lehramt für Deutsch als Fremdsprache' an der Universität Trakya unterscheiden sich bei der Aufnahme des Fachstudiums von den Ergebnissen der Sprachstandprüfung, die am Ende der einjährigen Vorbereitungsklasse durchgeführt wird. Dieser Ausgangspunkt scheint auch für Abteilungen anderer Universitäten der Fall zu sein, die sich im gleichen Umfang befinden. Diesbezüglich ist es Ziel dieses Beitrags, den Faktor 'Sommerferien' bei diesem Übergang deskriptiv aufzudecken. Die Fragestellung, wie die Lernenden ihre Sommerferien bezüglich des Deutschlernens verbracht haben, war dabei entscheidend. Um eine Antwort darauf zu bekommen, wurden Lernende zu dem Faktor 'Sommerferien' mittels qualitativer Erhebungsmethode befragt. Die Resultate wurden mit Lernstrategien angeknüpft. Aus der Forschung resultierten zwei Ansätze: Erstens sollten einige Konzepte entwickelt werden, damit die Lernenden ihre Deutschkenntnisse während ihrer Sommerferien kontinuierlich weiterentwickeln. Zweitens sollten einige Maßnahmen getroffen werden, womit DaF_Lernende ihre gelernten Deutschkenntnisse wenigstens stabil halten können.
Bu çalışmada Türkiye'de ilköğretim kurumlarından itibaren en az bir yabancı dil öğretilmesine rağmen neden Ölçme Seçme ve Yerleştirme Merkezi (ÖSYM) tarafından hazırlanan, uygulanan ve değerlendirilen sınavlarda birçok kişinin istenilen başarıya ulaşamadığı, özellikle dört yıl yabancı dilde eğitim alan Almanca öğretmenlik lisans mezunu öğretmen adaylarının Öğretmenlik Alan Bilgisi Testinden neden istedikleri sonuçları elde edemedikleri araştırılmış, sınavlara girenlerin sınav sorularını ne ölçüde doğru cevaplandırdıkları veya sorulara cevap verirken neden hata yaptıkları sorularına cevap aranmıştır. Araştırmaya ilişkin veriler rastgele seçilen ÖSYM'nin hazırlamış olduğu sınavlardan alınan örnek sorulardan oluşturulan bir örnek sınavın Trakya Üniversitesi lisans öğrencilerine uygulanması suretiyle toplanmış, okuduğunu anlama, çeviri gibi birçok soru tipinde iyi sonuçlar elde edilmesi ancak dilbilgisine ilişkin soruların çok azının doğru cevaplandırılması sonucunda araştırma cevap şıkları arasında en az bir adet bağlaç bulunan sorular ile sınırlandırılmıştır. Bağlaçlar üzerine yapılan inceleme, ÖSYM tarafından hazırlanan ve uygulanan sınavlarda günlük yaşamda sık kullanılan bağlaçların yanı sıra çok nadir kullanılan bağlaçlara da yer verildiğini ve sorulara doğru cevap verebilmek için lisans süresince kullanılan dilbilgisi kitaplarındaki konuları tekrar etmenin yeterli olmayacağı, merkezi sınavlarda yer alan soruları doğru cevaplandırabilmek için özellikle şıklarda yer alan uygun bir kelime ile tamamlanması gereken cümlelerin anlamlarının çok iyi anlaşılması ve bunun için de çok geniş bir kelime hazinesine sahip olunması ve öte yandan bağlaçların üstlenebilecekleri tüm işlevlerini ve anlamsal ve sözdizimsel özelliklerini bilmek gerektiğini ortaya koymuştur. Ancak Almanca Öğretmenliği lisans eğitimi süresince kullanılan dilbilgisi kitapları incelendiğinde, bunlarda her bir bağlaca yer verilmediği gibi bağlaçların sunuluş biçiminde de farklılıkların olduğu ve her kaynakta bağlaçların her bir anlamsal ve sözdizimsel özelliğine yer verilmediği, bu nedenle Almanca öğretmen adaylarının sınavlarda başarılı olmak için lisans süresince aldıkları eğitimin yanı sıra mutlaka daha başka kaynaklardan da aydalanarak bireysel olarak ek çalışmalar yapmaları gerektiği sonucuna varılmıştır.
Kadınlar ve erkekler yapısal farklılıkları dışında birçok açıdan ayrılıklar göstermektedir. Bu ayrılıklar sadece fiziki görünüşte, giyimde, hareketlerde değil, genel olarak davranış, uygulama, düşünme, alışkanlıklar ve dil gibi alanlarda da görülebilmektedir. Ayrıca kadın ve erkeğe sahip oldukları biyolojik cinsiyetleri haricinde toplumsal roller de yüklenmektedir. Bu roller de kadın ve erkek arasında mevcut olan farklılıkların toplumsal açıdan etkileşime girmesini sağlamaktadır. Toplumsal etkileşimler kadınlarla erkeklerin dillerinde de gözlemlenebilmektedir. Dil, bu durumda biyolojik cinsiyet ve toplumsal rol etkileşimlerinin bir arada bulunduğu bir öğedir. Aynı dili konuşmalarına, dilin aynı sözcükleri ve kurallarını kullanmalarına rağmen, kadınların dilleri ile erkeklerin dilleri arasında farklılıklar bulunmaktadır. Genel olarak deskriptif - analitik yöntemle ilerleyecek olan bu çalışmanın amacı Türkiye'deki kadın dili araştırmalarına göz atmaktır. Çalışmanın kuramsal kısmında, Türkiye'de yapılmış olan kadın dili araştırmalarına değinilerek hangi durumda olduğunun gözden geçirilmesi düşünülmektedir. Dünyada kadın ve erkek dili ile ilgili çalışmalara 20. yüzyıl başlarında ağırlık verilmiştir. Bu çalışmalar sadece içeriksel değil, aynı zamanda sözlüksel, retorik ve sözdizimsel bağlamda da gerçekleştirilmiştir. Özellikle Almanya’da oldukça geniş bir araştırma alanı olan bu konunun, Türkiye'de bu kadar geniş çapta ele alınmadığı görülmektedir. Çalışmanın uygulama bölümünde medyadaki kadın dili ele alınacaktır. Bu kısımda medya metinleri değerlendirilerek söz konusu metinlerdeki kadın dili incelenecektir. Kadın dili değişkeninin görsel medyada hangi özellikleri ile ortaya çıktığı, ne şekilde gözlemlenebildiği gerek içeriksel, gerekse sözlüksel, retorik ve sözdizimsel bağlamda incelenecektir.
Almanca dilbilgisinde tümcenin temel öğeleri genellikle eylem temel alınarak yapılır. Türkçe dilbilgisi için bu durum sözde kalmaktadır. Çünkü öğeler genellikle eylemin birleşim değeri göz önünde bulundurulmadan, o anda tümcede rastlantısal olarak bulunan öğeler olarak değerlendirilmektedir. Dolayısıyla, nitel araştırma yöntemiyle internetten ve basılı dokümanlardan elde edilen verilerin yorumlanmasıyla oluşan bu makalede, birleşim değeri çerçevesinde değerlendirme yapılmış olup eylemin gerektirdiği öğeler buna göre ele alınmalıdır. Diğer bir sorun da, Almanca dilbilgisi bağlamında üzerinde genel anlamda uzlaşılan, ancak Türkçede tartışmalı olan nesne terimi ve kavramıdır. Dolayısıyla bu çalışmada genel anlamda nesne kavramından yola çıkılarak sonilgeçli nesne kavramına gelinecektir. Amaç, Türkçe - Almanca nesne türlerini karşılaştırmak değil, Türk dili bağlamında “nesne”nin daha iyi anlaşılmasını sağlamak için Almancadan da örnekler vermektir. Nesne teriminin Türkçede Akkusativobjekt ile sınırlı tutulmasının yanlış olduğu ve çıkma durumu nesnesi, bulunma durumu nesnesi, sonilgeçli nesne gibi terimlerin dilbilgisel bir gerçek olduğu sonucuna varılmıştır. Bu bağlamda Türkçede eyleyen (Aktant) olarak sonilgeçli nesne (Postpositionalobjekt) gerektiren eylemler olduğu saptanmıştır.
Causative, which is analyzed in the context of voice, differs widely in Turkish and German languages. A causative can be obtained nearly from each verb in Turkish language while this category is not productive in German Language. Like prefixes, which are of great importance in German language, the causative has the same significance in Turkish language. Causatives can be divided into three: a) lexical causative, causative existing in words' own meaning; for instance, there exists such a relationship between the words "slide" and "fall"; b) morphological causative consists of morphemes (öl-dür-t-mek); c) whereas, the context is important for the operant causative. When we say “It smells gas in here’ it may have been intended to open a window and we can make it done. There is a direct connection between the causative and causality. Because, in causative instead of doing something directly, it may be caused to be done or occurred. The notion of causative in German has been reviewed in the semantic context at a low degree. This is because of the fact that, morphological causative verbs are fewer and new causative voices can't be formed. However, this issue has been handled in a very detailed manner especially at morphological level in Turkish language. There is even fine detail under the title causative itself. The most important characteristic of causative is to change the combination value of the verbs. However, the relation between causative and passive is just the opposite of this and asymmetric. Structures having semantic similarities with causatives and named as Funktionsverbgefüge (put into practice = apply) in German exist. Reciprocal voices and reflexive voices, the most important voices of Turkish language, generally allow the formation of causative verb.
Das Buch gegen das Verschwinden ist Ulrike Almut Sandigs zweite Prosaveröffentlichung und kann mit dem Etikett lyrische Prosa versehen werden, da die Autorin bisher doch zumeist im lyrischen Bereich veröffentlicht hat. Klar und hart sind die Sätze, überlegt durchdacht die Szenen, ausgefeilt die Erzählstrukturen, die sich manchmal jedoch erst später strukturieren. Und doch findet Ulrike Almut Sandig einen Ton, der die Geschichte Die Blauen Augen Deiner Mutter in einer schwebenden Ambivalenz hält" (Schröder 2015). Sicher, man könnte all das rein realistisch lesen und daneben auch versuchen sich eine Meinung über den Gezi-Park zu bilden, als würde man eine rationale Erklärung für die Thematik finden. "Und doch sickert in die Grundfesten des Plausiblen immer wieder eine Form von Unheimlichkeit und Restunerfindlichkeit ein. Sandig torpediert Gewissheiten, die ihrer Figuren und die ihrer Leser" (ebd.). Ohne sich einem Erzählschema unterzuordnen, ist allen Texten in diesem Band eines gemeinsam: Etwas kommt abhanden, löst sich in Luft auf, verschwindet. Zurück bleiben Vereinsamte, die, wenn überhaupt, über das Erzählen xistieren.
Oral anticoagulant-associated intracerebral hemorrhage (OAC-ICH) accounts for nearly 20% of all ICH. The number of patients with an indication for oral anticoagulant therapy (OAT) increases with increasing age. OAT became less complicate with the introduction of non-vitamin K oral anticoagulants (NOAC) OAT because of easier handling, favorable risk-benefit profile, reduced rates of ICH compared to vitamin K antagonists and no need for routine coagulation testing. Consequently, despite a better safety profile of NOAC the number of patients with OAC-ICH will increase. The mortality and complication rates of OAC-ICH are high and therefore they are the most feared complication of OAT. Immediate normalization of coagulation is the main goal and therefore knowledge of pharmacodynamics and coagulation status is essential. Laboratory measurements of anticoagulant activity in NOAC patients is challenging as specific tests are not widely available. More accessible tests such as the prothrombin time and activated partial thromboplastin time have important limitations. In dabigatran-associated ICH 5 g Idarucizumab should be administered. In rivaroxaban and apixaban-associated ICHs administration of andexanet alpha should be considered. Prothrombin complex concentrate may be considered if andexanet alpha is not available or in case of an ICH associated with edoxaban.
The authors review the current status of percutaneous left atrial appendage (LAA) occlusion therapy in patients with atrial fibrillation with the goal to prevent ischemic stroke and systemic embolism and to reduce oral anticoagulation associated bleeding. While we cover the historical and also surgical background, and all tested devices, the main focus rests on the single currently U.S. Food and Drug Administration (FDA) approved LAA occluder, the WATCHMAN device, and its approval process. The authors also give a critical appraisal beyond the review of mere facts, trying to put the current data into perspective.
Background: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure.
Methods: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated.
Discussion: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment.
Trial registration: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).
Different response of Ptch mutant and Ptch wildtype Rhabdomyosarcoma toward SMO and PI3K inhibitors
(2018)
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma with poor prognosis. RMS frequently show Hedgehog (HH) pathway activity, which is predominantly seen in the embryonal subtype (ERMS). They also show activation of Phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) signaling. Here we compared the therapeutic effectiveness and the impact on HH target gene expression of Smoothened (SMO) antagonists with those of the PI3K inhibitor pictilisib in ERMS with and without mutations in the HH receptor Patched1 (PTCH). Our data demonstrate that growth of ERMS showing canonical Hh signaling activity due to Ptch germline mutations is efficiently reduced by SMO antagonists. This goes along with strong downregulation of the Hh target Gli1. Likewise Ptch mutant tumors are highly responsive toward the PI3K inhibitor pictilisib, which involves modulation of AKT and caspase activity. Pictilisib also modulates Hh target gene expression, which, however, is rather not correlated with its antitumoral effects. In contrast, sporadic ERMS, which usually express HH target genes without having PTCH mutation, apparently lack canonical HH signaling activity. Thus, stimulation by Sonic HE (SHH) or SAG (Smoothened agonist) or inhibition by SMO antagonists do not modulate HH target gene expression. In addition, SMO antagonists do not provoke efficient anticancer effects and rather exert off-target effects. In contrast, pictilisib and other PI3K/AKT/mTOR inhibitors potently inhibit cellular growth. They also efficiently inhibit HH target gene expression. However, of whether this is correlated with their antitumoral effects it is not clear. Together, these data suggest that PI3K inhibitors are a good and reliable therapeutic option for all ERMS, whereas SMO inhibitors might only be beneficial for ERMS driven by PTCH mutations.
The opportunistic pathogen Acinetobacter baumannii is able to grow on carnitine. The genes encoding the pathway for carnitine degradation to the intermediate malic acid are known but the transporter mediating carnitine uptake remained to be identified. The open reading frame HMPREF0010_01347 (aci01347) of Acinetobacter baumannii is annotated as a gene encoding a potential transporter of the betaine/choline/carnitine transporter (BCCT) family. To study the physiological function of Aci01347, the gene was deleted from A. baumannii ATCC 19606. The mutant was no longer able to grow on carnitine as sole carbon and energy source demonstrating the importance of this transporter for carnitine metabolism. Aci01347 was produced in Escherichia coli MKH13, a strain devoid of any compatible solute transporter, and the recombinant E. coli MKH13 strain was found to take up carnitine in an energy‐dependent fashion. Aci01347 also transported choline, a compound known to be accumulated under osmotic stress. Choline transport was osmolarity‐independent which is consistent with the absence of an extended C‐terminus found in osmo‐activated BCCT. We propose that the Aci01347 is the carnitine transporter mediating the first step in the growth of A. baumannii on carnitine.
Danger signals in trauma
(2018)
This review summarizes a short list of currently discussed trauma-induced danger-associated molecular patterns (DAMP). Due to the bivalent character and often pleiotropic effects of a DAMP, it is difficult to describe its “friend or foe” role in post-traumatic inflammation and regeneration, both systemically as well locally in tissues. DAMP can be used as biomarkers to indicate or monitor disease or injury severity, but also may serve as clinically applicable parameters for better indication and timing of surgery. Due to the inflammatory processes at the local tissue level or the systemic level, the precise role of DAMP is not always clear to define. While in vitro and experimental studies allow for the detection of these biomarkers at the different levels of an organism—cellular, tissue, circulation—this is not always easily transferable to the human setting. Increased knowledge exploring the dual role of DAMP after trauma, and concentrating on their nuclear functions, transcriptional targets, release mechanisms, cellular sources, multiple functions, their interactions and potential therapeutic targeting is warranted.
Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases). We found a sensitivity and specificity of 100% for detection of ALK rearrangements using the OFA panel. In addition, targeted next generation sequencing allowed us to analyze a set of 23 driver genes in a single assay. Besides EML4-ALK (11/52 cases), we detected EZR-ROS1 (1/52 cases), KIF5B-RET (1/52 cases) and MET-MET (4/52 cases) fusions. All EML4-ALK, EZR-ROS1 and KIF5B-RET fusions were confirmed by multiplexed targeted next generation sequencing assay (Oncomine Solid Tumor Fusion Transcript Kit, Thermo Fisher Scientific). All cases with EML4-ALK rearrangement were confirmed by Alk immunohistochemistry and all but one by ALK FISH. In our experience, targeted next-generation sequencing is a reliable and timesaving tool for multiplexed detection of targetable rearrangements. Therefore, targeted next-generation sequencing represents an efficient alternative to time-consuming single target assays currently used in molecular pathology.
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
Objective. Traumatic injury or severe surgery leads to a profound immune response with a diminished functionality of monocytes and subsequently their IL-1β release. IL-1β plays an important role in host immunity and protection against infections. Its biological activation via IL-1β-precursor processing requires the transcription of inflammasome components and their activation. Deregulated activity of NOD-like receptor inflammasomes (NLR) like NLRP3 that leads to the maturation of IL-1β has been described in various diseases. While the role of other inflammasomes has been studied in monocytes, nothing is known about NLRP3 inflammasome after a traumatic injury. Here, the role of the NLRP3 inflammasome in impaired monocyte functionality after a traumatic injury was analyzed.
Measurements and Main Results. Ex vivo-in vitro stimulation of isolated CD14+ monocytes with lipopolysaccharide (LPS) showed a significantly higher IL-1β secretion in healthy volunteers (HV) compared to trauma patients (TP) after admission. Reduced IL-1β secretion was paralleled by significantly lowered gene expression of NLRP3 in monocytes from TP compared to those of HV. Transfection of monocytes with NLRP3-encoding plasmid recovered the functionality of monocytes from TP regarding the IL-1β secretion.
Conclusions. This study demonstrates that CD14+ monocytes from TP are significantly diminished in their function and that the presence of NLRP3 components is necessary in recovering the ability of monocytes to produce active IL-1β. This recovery of the NLRP3 inflammasome in monocytes may imply a new target for treatment and therapy of immune suppression after severe injury.
Species identification of adult African blowflies (Diptera: Calliphoridae) of forensic importance
(2017)
Necrophagous blowflies can provide an excellent source of evidence for forensic entomologists and are also relevant to problems in public health, medicine, and animal health. However, access to useful information about these blowflies is constrained by the need to correctly identify the flies, and the poor availability of reliable, accessible identification tools is a serious obstacle to the development of forensic entomology in the majority of African countries. In response to this need, a high-quality key to the adults of all species of forensically relevant blowflies of Africa has been prepared, drawing on high-quality entomological materials and modern focus-stacking photomicroscopy. This new key can be easily applied by investigators inexperienced in the taxonomy of blowflies and is made available through a highly accessible online platform. Problematic diagnostic characters used in previous keys are discussed.
2010 yılında Polonya'nın Varşova kentinde "Vielheit und Einheit der Germanistik" teması ile gerçekleştirilen 12. Uluslararası Germanistik Kongresi’nin ardından 13. Uluslararası Germanistik Kongresi 2015 yılında "Germanistik zwischen Tradition und Innovation" teması ile Çin Halk Cumhuriyeti Şanghay Tongji Üniversitesi'nde 23-30 Ağustos 2015 tarihlerinde düzenlendi. Türkiye'nin de aralarında bulunduğu 96 ülkeden kongreye katılan 1200'ün üzerinde değerli akademisyen ve araştırmacı kongrede bildirilerini sundular.
Der 13. Weltkongress der Internationalen Vereinigung für Germanistik (IVG) fand vom 23.08.2015 bis zum 30.08.2015 unter dem Motto "Germanistik zwischen Tradition und Innovation" in Shanghai/China statt. Gastgeber dieses vielfältigen und reichhaltigen internationalen Kongresses war die Tongji-Universität. Mehr als 1200 Teilnehmerinnen und Teilnehmer aus 69 Ländern haben an diesem Kongress, der alle fünf Jahre organisiert wird, teilgenommen. Auch die Türkei beteiligte sich mit ca. 30 Wissenschaftlerinnen und Wissenschaftlern aus Edirne bis Van an diesem Kongress.
Das wissenschaftliche Interesse auf dem Feld der Germanistik ist in den letzten Jahren in Rumänien, auch dank Herta Müller, die 2009 den Nobelpreis für Literatur bekommen hat, stark gestiegen. Nach dem letzten Kongress der Germanisten Rumäniens 2012 in Bukarest wurde der 10. Kongress der Germanisten Rumäniens vom 01. bis 04. Juni 2015 in der Aula an der Universität Transilvania in Braşov/Kronstadt veranstaltet. Die Tagung wird alle drei Jahre an jeweils wechselnden Hochschulen vom dortigen Germanistik-Fachbereich veranstaltet, was zeigt, dass die Germanistik in Rumänien an vielen Orten durch zum Teil kleine, aber aktive Lehrstühle vertreten ist.
Considering the misunderstanding of the particles used as an adverb by itself in closely related languages, we will try to provide the comprehension of sense of language about this area, which is missing in German. For this purpose, opposite language pairs seeming logical and etimological proofs about language variation will be presented. Firstly, we will try to explain what the sense of language is. We believe that it is more appropriate to say 'language acquisition' which can be acquired and developed by means of activities in foreign language classes. Examples verify this. In the conclusion, some other clarifying questions follow.
Sowohl international als auch national ist erkennbar, dass Länder in Bereichen Wirtschaft, kommunikative und informative Technologien, Politik, Bildung und Gesellschaft in unterschiedlicher Art und Weise mit kulturellen bzw. interkulturellen Tendenzen konfrontiert sind. Diese Tatsachen reflektieren somit, dass Gesellschaften immer mehr mit interkulturellen Herausforderungen in Kontakt kommen. Interkulturelles Lernen, Interkulturalität und interkulturelle Kompetenz enthalten gleichfalls im gegenwärtigen und modernen Fremdsprachenunterricht eine bedeutende Rolle und ein wichtiges Aufgabenfeld.
Present conditions are affecting the educational process and as a result of these changes restructuring these processes is essential. There is no doubt that in teaching foreign languages in general and in particular German as a foreign language, one of the prerequisites to gain for providing a qualified German language teaching is the training of qualified and well equipped German teachers. In this context one of the substantial competences in the training process is the linguistic competence. It is aimed that at the end of their study period, German language teacher candidates should have the ability of using the German language in written and spoken area and creating models for their prospective students.
Despite the new technological developments writing has not lost its importance; on the contrary, ist importance has been increasing day by day. German teacher candidates should be trained to be able to express themself written as well as verbally to respond to their students' writing needs. For this reason students who graduated from the German Language Teaching Department of Hasan Ali Yücel Faculty of Education of Istanbul University in 2013-2014 academic year were asked to evaluate their writing competence.
The self assessments results of the candidate teachers are going to be compared with the results of the writing competence part of the Goethe Zertifikat C1 examination. The aim is to determine proficiency in the duration of 4 years. The results also constitute the scientific basis of curricular discussions in the field of writing courses of the German Language Teaching Department.
In den letzten Jahren ist eine kaum überschaubare Anzahl von Büchern zum Thema Körpermodifikationen erschienen, was aber bisher fehlt, ist ein klares Verständnis und eine kurze überblicksartige Dаrstellung der gängigen Formen der Fachausdrücke im Bereich der ästhetischen Chirurgie, die dem linguistisch-medizinisch Interessierten einen prägnanten Einblick in die Herkunft, die Wоrtbildung und die Häufigkeit und vergleichende Analyse der medizinischen Termini liefert. Deshalb soll in diesem Artikel versucht werden, einen kleinen Beitrag zur Bildung und Entwicklung ästhetisch-medizinischer Terminologie zu leisten. Bei dem vorliegenden Artikel handelt es sich um eine deskriptive Terminоlоgiearbeit, deren Ziel es ist, die verwendete Terminologie eines Fachgebietes zu beschreiben und aufzuzeichnen
This article focuses primarily on three areas: First the article deals with Alfred Döblin's concept of the novel and the function of the montage technique from his perspective. Secondly, the article draws attention to the fact that Alfred Döblin, a neurologist by profession, who later dedicated himself exclusively to his writing, used the montage technique intensively in his great city novel Berlin Alexanderplatz. The technique, which operates at different levels of language, narrative technique and plot, is demonstrated by selected examples from the novel. In each case the intention of the novelist is discussed. The article considers whether individual accumulating elements accord with the wholeness of the novel, and if so, how this interesting synthesis occurs. The final focus is on his efforts to use the montage technique to portray the big city. In the case of Berlin Alexanderplatz, this effort ultimately ends with a big city epic. In this study, we consider how Döblin used the montage technique in Berlin Alexanderplatz, which was central, and new for German literature at that time. Additionally, narrative styles and techniques as parables, paraboles, sound associations, word and rhyme repetition and relevant passages are supported by quotations from the novel.
Else LaskerSchüler (1869-1945), among the significant expressionist woman writers, did not only suffer from being both a woman and author, but also had to struggle under difficulties of being a hebrew. In this paper, especially the letter novel titled "Der Malik : Eine Kaisergeschichte" has been handled in the light of Homi K. Bhabha's 'Third Space Theory'. In regard to this, the "Third Space", which is defined by postcolonial theoretician Homi K. Bhabha as an extra place where minorities and outcast groups can express themselves in his work "The Location of Culture", is adapted to the literary "Orient" and defined once again in Else Lasker-Schüler's novel as it was never approached and interpreted before. In this sense, this supports the relevance to analyze her mentioned works in terms of the "Third Space Theory". Else Lasker-Schüler constructed a new world for herself through literature; her works were her life and her life was her works.
Black Humor, Brimstone Grotesque and A Terrifying Scenery in the work of Thomas Bernhard named "The Painter". Thomas Bernhard (1931-1989) is one of the most important writers of the Austrian postwar literature. All of his works reflect the characteristics of that period. "Bernhardesque" literature (just as the "Kafkaesque") always shapes the language and brings it out forcing the maximum limits of the semantics and stylistics expression facilities of the language. Bernhard generally figures out the inner world of the modern people psychologically disturbed and represents their wholly technological, noncommunicative and hostile environment in his works, especially features ironic, absurd, and grotesque and a little bit comic elements. Thomas Bernhard, a worldwide famous writer, poet and playwright, wrote a prose novel entitled "Ereignisse" (Events) that includes thirty-one extraordinary stories in 1957. These are the stories can be read both independently from each other and also in coherence. This study is aimed to analyses one of these works, the twelfth one in the light of eclectical way, mostly involves 'black humor' which is named "Der Anstreicher" (The Painter). The term Black Humor is generally defined for the works characterized by a desperate, sardonic humor intended to induce laughter as the appropriate response to the apparent meaninglessness and absurdity of existence. This short story of Bernhard tells about an "Event" derived its theme from the daily life and can be thought as a simple work accident but it brings a death to his main character. Narrator narrates this fatal and ordinary event with a horrific, grotesque and agonizing absurdity and as we try to figure out in this study; The Painter includes 'Black Humor' in this context.
Biological invasions are frequently studied topics in ecological research. Unfortunately, within invasion ecology parasite-associated aspects such as parasite impacts on new environments and on local host populations are less well-studied. Round gobies migrating from the Ponto-Caspian region into the Rhine River system are heavily infested with the Ponto-Caspian acanthocephalan parasite Pomphorhynchus laevis. As shown by experimental infestations the acanthocephalans occur as pre-adults in host-encapsulated cysts within the internal organs of the migrating gobies, but remain infective for their definitive host chub. Recently, we described the occurrence of larvae of another parasite, the invasive eel swim bladder nematode Anguillicola crassus, in these Pomphorhynchus cysts. In the present study, we could prove the infectivity of the nematode larvae for European eels for the first time. After experimental inoculation of Pomphorhynchus cysts occasionally infested with A. crassus larvae, the nematodes grow to maturity and reproduce whereas all P. laevis were unviable. We therefore postulate that the nematode larvae behave like immunological hitchhikers that follow a “Trojan horse strategy” in order to avoid the paratenic host’s immune response. Accordingly, the interaction between both invasive parasites gives first evidence that the invasional meltdown hypothesis may also apply to parasites.
New technologies and therapies designed to facilitate development of personalized treatments are rapidly emerging in the field of biomedicine. Strikingly, the goal of personalized medicine refined the concept of therapy by developing cell-based therapies, the so-called “living drugs”. Breakthrough advancements were achieved in this regard in the fields of gene therapy, cell therapy, tissue-engineered products and advanced therapeutic techniques. The Advanced Therapies in Healthcare symposium, organized by the Clinical Research Center Department of Sidra Medicine, in Doha, Qatar (October 2017), brought together world-renowned experts from the fields of oncology, hematology, immunology, inflammation, autoimmune disorders, and stem cells to offer a comprehensive picture of the status of worldwide advanced therapies in both pre-clinical and clinical development, providing insights to the research phase, clinical data and regulatory aspects of these therapies. Highlights of the meeting are provided in this meeting report.
Background: Histological evidence suggests that autism spectrum disorder (ASD) is accompanied by a reduced integrity of the grey-white matter boundary. This has also recently been confirmed by a structural neuroimaging study in vivo reporting significantly reduced grey-white matter tissue contrast (GWC) in adult individuals (18–42 years of age) with ASD relative to typically developing (TD) controls. However, it remains unknown whether the neuroanatomical differences in ASD at the grey-white matter boundary are stable across development or are age-dependent.
Methods: Here, we examined differences in the neurodevelopmental trajectories of GWC in a cross-sectional sample of 77 male ASD individuals and 76 typically developing (TD) controls across childhood and early adulthood (from 7 to 25 years).
Results: Using nested model comparisons, we first established that the developmental trajectory of GWC is complex in many regions across the cortex and includes linear and non-linear effects of age. Second, while ASD individuals have significantly reduced GWC overall, these differences are age-dependent and are most prominent during childhood (< 15 years).
Conclusions: Taken together, our findings suggest that differences in GWC in ASD are unlikely to reflect atypical grey matter cytoarchitecture alone, but may also represent other aspects of the cortical architecture such as age-dependent variability in myelin integrity.
Background: The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC).
Methods: First, miRNA expression profiles were determined in exosomes derived from the plasma of 15 TNBC patients before neoadjuvant therapy using a quantitative TaqMan real-time PCR-based microRNA array card containing 384 different miRNAs. Forty-five miRNAs associated with different clinical parameters were then selected and mounted on microRNA array cards that served for the quantification of exosomal miRNAs in 435 BC patients before therapy and 20 healthy women. Confocal microscopy, Western blot, and ELISA were used for exosome characterization.
Results: Quantification of 45 exosomal miRNAs showed that compared with healthy women, 10 miRNAs in the entire cohort of BC patients, 13 in the subgroup of 211 HER2-positive BC, and 17 in the subgroup of 224 TNBC were significantly deregulated. Plasma levels of 18 exosomal miRNAs differed between HER2-positive and TNBC subtypes, and 9 miRNAs of them also differed from healthy women. Exosomal miRNAs were significantly associated with the clinicopathological and risk factors. In uni- and multivariate models, miR-155 (p = 0.002, p = 0.003, respectively) and miR-301 (p = 0.002, p = 0.001, respectively) best predicted pathological complete response (pCR).
Conclusion: Our findings show a network of deregulated exosomal miRNAs with specific expression patterns in exosomes of HER2-positive and TNBC patients that are also associated with clinicopathological parameters and pCR within each BC subtype.
The challenges posed by climate and land use change are increasingly complex, with ever-increasing and accelerating impacts on the global environmental system. The establishment of an internationally harmonized, integrated, and long-term operated environmental monitoring infrastructure is one of the major challenges of modern environmental research. Increased efforts are currently being made in Europe to establish such a harmonized pan-European observation infrastructure, and the European network of Long-Term Ecological Research sites – LTER-Europe – is of particular importance. By evaluating 477 formally accredited LTER-Europe sites, this study gives an overview of the current distribution of these infrastructures and the present condition of long-term environmental research in Europe. We compiled information on long-term biotic and abiotic observations and measurements and examined the representativeness in terms of continental biogeographical and socio-ecological gradients. The results were used to identify gaps in both measurements and coverage of the aforementioned gradients. Furthermore, an overview of the current state of the LTER-Europe observation strategies is given. The latter forms the basis for investigating the comparability of existing LTER-Europe monitoring concepts both in terms of observational design as well as in terms of the scope of the environmental compartments, variables and properties covered.
We examined alterations in E/I-balance in schizophrenia (ScZ) through measurements of resting-state gamma-band activity in participants meeting clinical high-risk (CHR) criteria (n = 88), 21 first episode (FEP) patients and 34 chronic ScZ-patients. Furthermore, MRS-data were obtained in CHR-participants and matched controls. Magnetoencephalographic (MEG) resting-state activity was examined at source level and MEG-data were correlated with neuropsychological scores and clinical symptoms. CHR-participants were characterized by increased 64–90 Hz power. In contrast, FEP- and ScZ-patients showed aberrant spectral power at both low- and high gamma-band frequencies. MRS-data showed a shift in E/I-balance toward increased excitation in CHR-participants, which correlated with increased occipital gamma-band power. Finally, neuropsychological deficits and clinical symptoms in FEP and ScZ-patients were correlated with reduced gamma band-activity, while elevated psychotic symptoms in the CHR group showed the opposite relationship. The current study suggests that resting-state gamma-band power and altered Glx/GABA ratio indicate changes in E/I-balance parameters across illness stages in ScZ.