Zum Qualitätsverständnis im E-learning und der Relevanz des Subjekts

In der vorliegenden Arbeit wird untersucht, welche Relevanz dem Subjekt bei der Qualitätsbestimmung bzw. -beurteilung von computerbasierten Lernformen (E-Learning) beizumessen ist und welche Konsequenzen dabei für künftige Konzeptionen abzuleiten sind. In diesem Zusammenhang erfolgt zunächst eine grundlegende Erörterung des Qualitätsbegriffes, worin die verschiedenen Sichtweisen und Dimensionen von Qualität im Bildungs- bzw. E-Learning-Kontext herausgearbeitet werden, und auf den Aspekt der Qualität als Ko-Produktion eingegangen wird. Anschließend erfolgt eine Erläuterung und genaue Darstellung der verschiedenen Formen und Charakteristik des E-Learnings, die sich insbesondere durch selbstgesteuertes bzw. selbstbestimmtes Lernen auszeichnet. Auf dieses Verständnis von selbstbestimmtem, autonomem Lernen wird im nächsten Kapitel Bezug genommen und dabei die zentralen Hypothesen der subjektwissenschaftlichen Lerntheorie nach Klaus Holzkamp herausgearbeitet. Dieser Theorieentwurf markiert nach Grotlüschen eine Abkehr von kausalen Ursache-Wirkungs-Modellen bestehender Lerntheorien und stellt gleichsam, neben dem Uses-And-Gratification-Approach und dem sozialökonomischen Ansatz, eine wesentliche Grundlage für das von Ulf-Daniel Ehlers konzipierte subjektive Qualitätsmodell im E-Learning dar. Ehe auf dieses Modell näher eingegangen wird, wird der Paradigmenwechsel systematisch nachskizziert und so die zunehmende Bedeutung des Subjekts im E-Learning-Kontext herausgestellt. Durch die Aufschlüsselung des Qualitätsverständnisses vom Subjekt her, gelingt es nun, eine Reihe unterschiedlicher, für den jeweiligen Lerner relevanter, Qualitätspräferenzen zu extrahieren, die sich im subjektiven Qualitätsmodell widerspiegeln und als Referenz für den jeweiligen (sozialen) Kontext gelten können, aus welchem Lerner E-Learning praktizieren. E-Learning-Arrangements bedürfen daher einer möglichst kongruenten Anpassung an die jeweiligen Lernsituationen und Kontexte. Dies erscheint nur möglich, wenn bei künftiger E-Learning-Entwicklung die bislang vielfach starre Orientierung auf einzelne Lernparadigmen einer dynamisch orientierten pragmatischen Herangehensweise weicht, die auch der Vielfalt an Lernmodalitäten am ehesten gerecht zu werden scheint. Die große Herausforderung wird sein, dass der Lerner in diesem Aushandlungsprozess seine Rolle als Ko-Produzent von Qualität im E-Learning behaupten kann und damit einen entscheidenden Beitrag zu einer Optimierung dieser noch verhältnismäßig jungen Lernform leistet

L-Carnitine and its transcriptional modulation

L-Carnitine ist ein semi-essentieller Nährstoff welcher aus den Aminosäuren Methionin und Lysin synthetisiert und mit der Nahrung aufgenommen wird. Besonders im Energiestoffwechsel erfüllt L-Carnitine wichtige Aufgaben. Es ermöglicht den Transport von langkettigen Fettsäuren (C16-C18) aus dem Zytosol in die mitochondrielle Matrix, wo diese Fettsäuren im Rahmen der β-Oxidation zu Acetyl-CoA abgebaut und folglich dem Krebszyklus zugeführt werden. L-Carnitine hat jedoch auch einen Einfluss auf die transkriptionelle Aktivität von verschiedensten Genen im gesamten Genom. (Litzlbauer et. al, 2006). Besonders die Menge an mRNA der humanen Acyltransferase-Gene CRAT, CPT1a und CPT2 werden nach Gabe von L-Carnitine hochreguliert. (Godárová et al, 2005). In dieser Diplomarbeit war es mir möglich diesen Effekt auch in der murinen Leberzelllinie TIB73 nachzuweisen. Durch quantitiative Real-Time PCR konnte ein bis zu 2-facher Anstieg der mRNA Menge des Gens der Carnitine-Acetyltransferase 4 Stunden nach Gabe von 80µM L-Carnitine nachgewiesen werden. In Vorarbeiten von Aniko Ginta Pordes konnte mittels Reportergen-Assays diejenige Gensequenz eingegrenzt werden welche für diesen „Carnitine-Effekt“ verantwortlich ist. Diese ist innerhalb von 342nt proximal des ersten Exons lokalisiert. Innerhalb dieser Sequenz konnten mittels theoretischer Promoteranalyse zahlreiche Bindungsstellen möglicher Transkriptions-faktoren definiert werden. Darunter fanden sich Consensus-Sequenzen für nukleare Faktoren wie Sp1, RXR, PPAR und Creb. Mittels MobilityShift Assays wurden diese Kandidaten überprüft. Die deutlichsten Effekte wurden bei der Analyse eines RXR Elements beobachtet, wobei in Supershift Experimenten besonders nach Gabe von PPARα und LXRα Antikörpern ein Abschwächungseffekt ausgemacht werden konnte. Der Einfluss von PPARα auf die Regulation der Expression des CRAT Gens konnte weiters mittels qPCR nachgewiesen werden, nachdem die Gabe von Fibraten zu eindeutigem Ansteigen der Expressionslevels von CRAT führte.L-carnitine, an amino acid-like compound synthesized from lysine and methionine, is essential for energy metabolism. It mediates the transport of long-chain fatty acids prone for ß-oxidation across the inner mitochondrial membrane into the matrix. Chip-screen analyses performed in our lab revealed that L-carnitine has a distinct regulative effect on the transcriptional activity on a significant part of the whole genome (Litzlbauer et. al, 2006). Especially the mRNA expression levels of human carnitine acyltransferase genes CRAT, CPT1A, CPT2 are regulated by L-carnitine (Godárová et al, 2005). We could provide evidence that the murine homologues CRAT, CPT1a, CPT2 and OCTN2 are similarly regulated on transcriptional level by L-carnitine. qPCR analysis of the murine carnitine acetyltransferase (CRAT) gene under supplementation of 80 µM L-carnitine for 4 hours resulted in a 2-fold increase on mRNA level. Reporter gene-assays with constructs carrying different segments of the promoter of the murine CRAT gene localized the “carnitine-effect” regulating element within a 342bp region. Within this region several putative transcription factor bindings sites could be identified with bioinformatical tools. The most promising transcription factor binding sites are SP1, PPARα, RXRα and CREB. Analysis of the retinoic X receptor alpha (RXRα) element with band shift and supershift assays revealed the influence of the transcription factors PPARα, LXRα and PPARbP on CRAT gene regulation under increasing L-carnitine concentration. Additional Southwestern Blot analysis supported the association of these promoter elements to a hypothetical transcription factor complex of the RXR locus. qPCR analysis of CRAT mRNA expression under PPARα-agonist supplementation supports the findings that PPARα is involved in the L-carnitine mediated gene regulation of CRAT. This indicates that CRAT gene-expression is a direct pharmacological target of these hyperlipidemic drugs

Irishness vs. Scottishness as reflected in Èilís Ní Dhuibhne's "The Dancers Dancing" and James Kelman's "Kieron Smith, Boy"

Die vorliegende Diplomarbeit ist eine komparative, imagologische Studie. Sie basiert auf zwei gegenwärtigen Büchern: Kieron Smith, Boy (2008) vom schottischen Autor James Kelman und The Dancers Dancing (1999) von der irischen Autorin Éilís Ní Dhuibhne. Imagologie beschäftigt sich im Allgemeinen mit der Repräsentation von Ländern und den ethnischen, regionalen und kulturellen Bildern oder Stereotypen in literarischen Werken. Den theoretischen Hintergrund der vorliegenden Diplomarbeit bildet das Eintreffen der ‘Irish and Scottish Studies’ als neues Forschungsfeld auf den Britischen Inseln. ‘Irish and Scottish Studies’ beschäftigen sich mit der komparativen und interdisziplinären Forschung der Geschichte, Kultur, Sprachen sowie Literaturen von Irland und Schottland. In den zwei Büchern Kieron Smith, Boy und The Dancers Dancing wurden irische und schottische Merkmale und Besonderheiten identifiziert indem Auto-Bilder analysiert wurden. Bereits publizierte soziologische Studien wurden als Hilfe herangezogen. Diese gefundenen Aspekte wurden unter den Begriffen ‚Sprache’, ‚Religion’, ‚Politik’, ‚Emigration und Immigration’, ‚Geografie – die Dichotomie zwischen Stadt und Land’, ‚Familie, Geschlechterrollen und das männliches Brotverdiener Modell’, ‚Aspekte der irischen/schottischen Kultur: der Céilí/Céilidh’ und ‚Berufe’ zusammengefasst und mit dem ‚Close Reading Approach’ genau analysiert. Schlussendlich wurde erarbeitet, ob sich Gemeinsamkeiten oder große Unterschiede in den Bildern der beiden Nationen finden lassen.The thesis at hand is a comparative, imagological analysis of The Dancers Dancing written by the Irish author Éilís Ní Dhuibhne and Kieron Smith, Boy written by the Scottish author James Kelman. Generally, imagology is concerned with the representation of countries and the national, ethnic, racial and cultural images or stereotypes in literature. The establishment of Irish and Scottish Studies as a field of enquiry in academia on the British Isles constitutes the theoretical background of the thesis. Irish and Scottish Studies conduct comparative and interdisciplinary research of the history, culture, languages and literatures of Ireland and Scotland. The main aim of the thesis is to establish whether Scottish and Irish connections and parallels that are promoted by Irish and Scottish Studies and suggested by history and, thus, images and aspects of Ireland/the Irish and Scotland/the Scottish can be found in literary works of Irish and Scottish authors. Both novels are analysed closely with the ‘Close Reading Approach’ in order to provide features and images that are particular to Scotland and Ireland and to explore the way authors are describing Irish and Scottish life. The main aspects that were found are summarised under the headings ‘Language’, ‘Religion’, ‘Politics’, ‘Geography – Dichotomy between the Rural and the Urban’, ‘Emigration and Immigration’, ‘Family, Gender Roles and the Male-Breadwinner-Model’, ‘Aspects of Irish and Scottish Culture: the Céilí/Céilidh’ and ‘Professions’. Finally, the main outcomes of the imagological study are compared and parallels and/or differences in the images of Ireland and Scotland established

Infarct-remodelled hearts with limited oxidative capacity boost fatty acid oxidation after conditioning against ischaemia/reperfusion injury

Aims Infarct-remodelled hearts are less amenable to protection against ischaemia/reperfusion. Understanding preservation of energy metabolism in diseased vs. healthy hearts may help to develop anti-ischaemic strategies effective also in jeopardized myocardium. Methods and results Isolated infarct-remodelled/sham Sprague-Dawley rat hearts were perfused in the working mode and subjected to 15 min of ischaemia and 30 min of reperfusion. Protection of post-ischaemic ventricular work was achieved by pharmacological conditioning with sevoflurane. Oxidative metabolism was measured by substrate flux in fatty acid and glucose oxidation using [3H]palmitate and [14C]glucose. Mitochondrial oxygen consumption was measured in saponin-permeabilized left ventricular muscle fibres. Activity assays of citric acid synthase, hydroxyacyl-CoA dehydrogenase, and pyruvate dehydrogenase and mass spectrometry for acylcarnitine profiling were also performed. Six weeks after coronary artery ligation, the hearts exhibited macroscopic and molecular signs of hypertrophy consistent with remodelling and limited respiratory chain and citric acid cycle capacity. Unprotected remodelled hearts showed a marked decline in palmitate oxidation and acetyl-CoA energy production after ischaemia/reperfusion, which normalized in sevoflurane-protected remodelled hearts. Protected remodelled hearts also showed higher β-oxidation flux as determined by increased oxygen consumption with palmitoylcarnitine/malate in isolated fibres and a lower ratio of C16:1+C16OH/C14 carnitine species, indicative of a higher long-chain hydroxyacyl-CoA dehydrogenase activity. Remodelled hearts exhibited higher PPARα-PGC-1α but defective HIF-1α signalling, and conditioning enabled them to mobilize fatty acids from endogenous triglyceride stores, which closely correlated with improved recovery. Conclusions Protected infarct-remodelled hearts secure post-ischaemic energy production by activation of β-oxidation and mobilization of fatty acids from endogenous triglyceride store

The role of ubiquitin ligases in cardiac disease

Rigorous surveillance of protein quality control is essential for the maintenance of normal cardiac function, while the dysregulation of protein turnover is present in a diverse array of common cardiac diseases. Central to the protein quality control found in all cells is the ubiquitin proteasome system (UPS). The UPS plays a critical role in protein trafficking, cellular signaling, and most prominently, protein degradation. As ubiquitin ligases (E3s) control the specificity of the UPS, their description in the cardiomyocyte has highlighted how ubiquitin ligases are critical to the turnover and function of the sarcomere complex, responsible for the heart’s required continuous contraction. In this review, we provide an overview of the UPS, highlighting a comprehensive overview of the cardiac ubiquitin ligases identified to date. We then focus on recent studies of new cardiac ubiquitin ligases outlining their novel roles in protein turnover, cellular signaling, and the regulation of mitochondrial dynamics and receptor turnover in the pathophysiology of cardiac hypertrophy, cardiac atrophy, myocardial infarction, and heart failure

The organization of care in pediatric radiotherapy across SIOP Europe affiliated centers:A multicenter survey in the framework of the 'Joint Action on Rare Cancers' project

BACKGROUND/PURPOSE: To reduce inequalities among SIOPE-affiliated countries, standard and optional levels to deliver 'Good Clinical Practice' compliant treatment in pediatric radiation oncology have been published. The aim of this project was to map the availability of pediatric radiotherapy resources across SIOPE-affiliated radiotherapy departments.MATERIALS/METHODS: An online survey with 34 questions was distributed to 246 radiotherapy departments across 35 SIOPE-affiliated countries. In addition to demographic data, 15 general items related to the organization of the radiotherapy process, and 10 radiotherapy-specific items were defined. For each of the 25 items, sum scores were calculated per center and country. Mann-Whitney U tests were used to analyze associations.RESULTS: Between March-June 2019, 121 departments (49 %) out of 31 countries (89 %) completed the survey. At center level, involvement of core disciplines in tumor boards (28 %), and integration of dedicated pediatric radiation therapy technologists (24 %) are limited, while rare &amp; complex brachytherapy procedures are performed in many centers (23 %). For general and radiotherapy-specific items respectively, a relevant variation of sum scores was observed across countries (Δgeneral: ≤10 points; ΔRT_specific: ≤5 points) and among centers within a country (Δgeneral: ≤9 points; ΔRT_specific: ≤6 points). Sum scores for general and radiotherapy-specific items were higher in countries with a high-income (p &lt; 0.01) and higher health development index (p &lt; 0.01). A larger annual number of irradiated pediatric patients was associated with higher sum scores for general items (p &lt; 0.01).CONCLUSION: This survey demonstrates the disparities in organization of pediatric radiotherapy departments between SIOPE-affiliated countries and centers within the same country. Investment is needed to reduce inequalities in pediatric radiotherapy care.</p

Autotaxin-LPA Signaling Contributes to Obesity-Induced Insulin Resistance in Muscle and Impairs Mitochondrial Metabolism

Autotaxin (ATX) is an adipokine that generates the bioactive lipid, lysophosphatidic acid (LPA). ATX-LPA signaling has been implicated in diet-induced obesity and systemic insulin resistance. However, it remains unclear whether the ATX-LPA pathway influences insulin function and energy metabolism in target tissues, particularly skeletal muscle, the major site of insulin-stimulated glucose disposal. The objective of this study was to test whether the ATX-LPA pathway impacts tissue insulin signaling and mitochondrial metabolism in skeletal muscle during obesity. Male mice with heterozygous ATX deficiency (ATX+/−) were protected from obesity, systemic insulin resistance, and cardiomyocyte dysfunction following high-fat high-sucrose (HFHS) feeding. HFHS-fed ATX+/− mice also had improved insulin-stimulated AKT phosphorylation in white adipose tissue, liver, heart, and skeletal muscle. Preserved insulin-stimulated glucose transport in muscle from HFHS-fed ATX+/− mice was associated with improved mitochondrial pyruvate oxidation in the absence of changes in fat oxidation and ectopic lipid accumulation. Similarly, incubation with LPA decreased insulin-stimulated AKT phosphorylation and mitochondrial energy metabolism in C2C12 myotubes at baseline and following palmitate-induced insulin resistance. Taken together, our results suggest that the ATX-LPA pathway contributes to obesity-induced insulin resistance in metabolically relevant tissues. Our data also suggest that LPA directly impairs skeletal muscle insulin signaling and mitochondrial function

Challenges for children and adolescents with cancer in Europe:The SIOP-Europe agenda

In Europe, 6,000 young people die of cancer yearly, the commonest disease causing death beyond the age of 1 year. In addition, 300,000-500,000 European citizens are survivors of a childhood cancer and up to 30% of them have severe long-term sequelae of their treatment. Increasing both cure and quality of cure are the two goals of the European paediatric haematology/oncology community. SIOPE coordinates and facilitates research, care and training which are implemented by the 18 European study groups and 23 national paediatric haematology/oncology societies. SIOPE is the European branch of the International Society of Paediatric Oncology and one of the six founding members of the European Cancer Organisation. SIOPE is preparing its strategic agenda to assure long-term sustainability of clinical and translational research in paediatric malignancies over the next 15 years. SIOPE tackles the issues of equal access to standard care and research across Europe and improvement of long term follow up. SIOPE defined a comprehensive syllabus for training European specialists. A strong partnership with parent, patient and survivor organisations is being developed to successfully achieve the goals of this patient-centred agenda. SIOPE is advocating in the field of EU policies, such as the Clinical Trials Regulation and the Paediatric Medicine Regulation, to warrant that the voice of young people is heard and their needs adequately addressed. SIOPE and the European community are entirely committed to the global agenda against childhood cancers to overcome the challenges to increasing both cure and quality of cure of young people with cancer

Bacterial Indole as a Multifunctional Regulator of Klebsiella oxytoca Complex Enterotoxicity.

Gastrointestinal microbes respond to biochemical metabolites that coordinate their behaviors. Here, we demonstrate that bacterial indole functions as a multifactorial mitigator of Klebsiella grimontii and Klebsiella oxytoca pathogenicity. These closely related microbes produce the enterotoxins tilimycin and tilivalline; cytotoxin-producing strains are the causative agent of antibiotic-associated hemorrhagic colitis and have been associated with necrotizing enterocolitis of premature infants. We demonstrate that carbohydrates induce cytotoxin synthesis while concurrently repressing indole biosynthesis. Conversely, indole represses cytotoxin production. In both cases, the alterations stemmed from differ- ential transcription of npsA and npsB, key genes involved in tilimycin biosynthesis. Indole also enhances conversion of tilimycin to tilivalline, an indole analog with reduced cytotox- icity. In this context, we established that tilivalline, but not tilimycin, is a strong agonist of pregnane X receptor (PXR), a master regulator of xenobiotic detoxification and intestinal inflammation. Tilivalline binding upregulated PXR-responsive detoxifying genes and inhib- ited tubulin-directed toxicity. Bacterial indole, therefore, acts in a multifunctional manner to mitigate cytotoxicity by Klebsiella spp.: suppression of toxin production, enhanced con- version of tilimycin to tilivalline, and activation of PXR

Immune evasion by proteolytic shedding of natural killer group 2, member D ligands in Helicobacter pylori infection

BackgroundHelicobacter pylori (H. pylori) uses various strategies that attenuate mucosal immunity to ensure its persistence in the stomach. We recently found evidence that H. pylori might modulate the natural killer group 2, member 2 (NKG2D) system. The NKG2D receptor and its ligands are a major activation system of natural killer and cytotoxic T cells, which are important for mucosal immunity and tumor immunosurveillance. The NKG2D system allows recognition and elimination of infected and transformed cells, however viruses and cancers often subvert its activation. Here we aimed to identify a potential evasion of the NKG2D system in H. pylori infection.MethodsWe analyzed expression of NKG2D system genes in gastric tissues of H. pylori gastritis and gastric cancer patients, and performed cell-culture based infection experiments using H. pylori isogenic mutants and epithelial and NK cell lines.ResultsIn biopsies of H. pylori gastritis patients, NKG2D receptor expression was reduced while NKG2D ligands accumulated in the lamina propria, suggesting NKG2D evasion. In vitro, H. pylori induced the transcription and proteolytic shedding of NKG2D ligands in stomach epithelial cells, and these effects were associated with specific H. pylori virulence factors. The H. pylori-driven release of soluble NKG2D ligands reduced the immunogenic visibility of infected cells and attenuated the cytotoxic activity of effector immune cells, specifically the anti-tumor activity of NK cells.ConclusionH. pylori manipulates the NKG2D system. This so far unrecognized strategy of immune evasion by H. pylori could potentially facilitate chronic bacterial persistence and might also promote stomach cancer development by allowing transformed cells to escape immune recognition and grow unimpeded to overt malignancy