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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.