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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.