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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.