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Der digitale Wandel wirkt sich auf das alltägliche Leben in der modernen Lebenswelt im 21. Jahrhundert aus. Ob im Berufs- oder Privatleben, digitale Medien sind nicht mehr aus dem alltäglichen Leben wegzudenken und sie erleichtern das Leben maßgeblich.
E-Learning wird insbesondere in der Erwachsenenbildung benutzt und diese Branche "boomt". Umstritten ist dennoch, ob digitale Medien und E-Learning in Schulen eingesetzt werden sollten und ob ein Lernen und Lehren mit neuen Medien sinnvoll ist. Derzeitig ist keine bundesweite einheitliche Lehrerausbildung bezüglich des Umgangs mit digitalen Medien im Kontext Lehren und Lernen und den damit verbundenen Herausforderungen vorhanden.
Es stellt sich die Frage, wie neue Medien im Unterricht verwendet werden und welche Aspekte beim Lehren zu beachten sind.
Deutschland und Europa
(2018)
Otmar Issing erörtert die Reaktionen in Deutschland auf die Pläne des französischen Präsidenten Macron aus dessen viel beachteter Rede zur Zukunft Europas an der Pariser Sorbonne. Issing wertet das Ergebnis der Sondierungsgespräche zwischen CDU/CSU und SPD als Abschied von der Vorstellung einer auf Stabilität gerichteten europäischen Gemeinschaft und mahnt an, den einheitlichen Markt und die damit verbundenen Freiheiten nicht durch überzogene Ambitionen zu gefährden und damit zunehmendes Misstrauen gegenüber Europa zu fördern.
Insbesondere in der geplanten Weiterentwicklung des ESM zu einem im Unionsrecht verankerten Europäischen Währungsfonds sieht Issing die Auslieferung der durch den Fonds zur Verfügung gestellten Mittel an eine politische Mehrheit. Zudem führe die Bestellung eines europäischen Finanzministers zur Schaffung einer die Währungsunion ergänzenden Fiskalunion und damit zur Verlagerung finanzpolitischer Kompetenz von der nationalen auf die europäische Ebene. In letzter Konsequenz bedeute dies eine Aufgabe des grundlegenden Prinzips der demokratischen Legitimierung und Kontrolle finanzpolitischer Entscheidungen.
Das Ergebnis der Sondierungsgespräche muss man als Abschied von der Vorstellung einer auf Stabilität gerichteten europäischen Gemeinschaft verstehen. Damit werden die Versprechen gebrochen, die man den Bürgern in Deutschland vor der Einführung des Euros gegeben hat.
Aim: To study the transepithelial transport characteristics of the polyamine putrescine in human intestinal Caco-2 cell monolayers to elucidate the mechanisms of the putrescine intestinal absorption.
Methods: The transepithelial transport and the cellular accumulation of putrescine was measured using Caco-2 cell monolayers grown on permeable filters.
Results: Transepithelial transport of putrescine in physiological concentrations ( > 0.5 mM) from the apical to basolateral side was linear. Intracellular accumulation of putrescine was higher in confluent than in fully differentiated Caco-2 cells, but still negligible (less than 0.5%) of the overall transport across the monolayers in apical to basolateral direction.EGF enhanced putrescine accumulation in Caco-2 cells by four fold, as well as putrescine conversion to spermidine and spermine by enhancing the activity of S adenosylmethionine decarboxylase. However, EGF did not have any significant influence on putrescine flux across the Caco- 2 cell monolayers. Excretion of putrescine from Caco-2 cells into the basolateral medium did not exceed 50 picomoles, while putrescine passive flux from the apical to the basolateral chamber, contributed hundreds of micromoles polyamines to the basolateral chamber.
Conclusion: Transepithelial transport of putrescine across Caco-2 cell monolayers occurs in passive diffusion, and is not influenced when epithelial cells are stimulated to proliferate by a potent mitogen such as EGF.
To analyze prospectively the interventional and clinical aspects of computed tomography-guided direct intratumoural injection of a novel chemotherapeutic administration and the parenchymal changes of tumour and necrosis in malignant liver tumours. Eight patients with 17 colorectal liver metastases were treated with a mean of 5.1 injections and nine patients with 13 hepatocellular carcinoma nodules with a mean of 3.1 treatments with computed tomography guided local applications of a novel cisplatin/epinephrine gel. This application provides a higher local and lower systemic drug concentration. Volumes of tumour and necrosis prior and after treatment were measured by computer generated volumetric analysis. Contrast enhanced studies verified pretherapeutic viable tumour volumes with a value of 77.4 ml in the metastases and 29.2 ml in the hepatocellular carcinoma nodules. Intratumoural drug application resulted in a significant increase of necrosis and a decrease in viable tumour volume to be 68.3 ml in metastases and 14.5 ml in hepatocellular carcinoma. Local therapy control rate for the follow up to 6 months was 38 and 71% for the group of metastases and hepatocellular carcinoma, respectively. Direct intratumoural injection of cisplatin/epinepthrine injectable gel is a feasible and good tolerated method and results in the development of a statistically significant increase in necrosis in malignant liver tumours. For hepatocellular carcinoma a higher local therapy control rate compared to colorectal metastases can be reported.
The proliferative stimulus of the epidermal growth factor (EGF) in human epithelial cells is mediated by its binding to the external domain of the EGF receptor (EGF-R). The purpose of this study was to investigate whether growth arrest of tumors treated with anti-EGFR MAb (EMD 55900) was dependent on EGF-R expression and distinct histopathologic criteria of those neoplasms. Nine different adenocarcinomas, squamous cell carcinomas and two neoplastic epithelial cell lines (A431 and Detroit 562), which were characterized by high EGF-R expression, were xenotransplanted onto NMRI-nu/nu mice and treated with an anti-EGF-R antibody (EMD 55900). Results revealed that EGF-R expression and distinct histopathologic growth patterns play an important role for the therapeutic effect of the EGF-R antibody treatment. Tumors with high epithelial cellularity and little connective tissue responded to EMD 55900 treatment to a greater degree of growth reduction than tumors with lower cellularity. These results will be helpful for evaluation of patients who would benefit from tumor therapy with anti-EGF-R antibody.
We generated transgenic tomato plants with altered expression of heat stress transcription factor HsfA1. Plants with 10-fold overexpression of HsfA1 (OE plants) were characterized by a singleHsfA1 transgene cassette, whereas plants harboring a tandem inverted repeat of the cassette showed cosuppression (CS plants) by posttranscriptional silencing of the HsfA1 gene connected with formation of small interfering RNAs. Under normal growth conditions, major developmental parameters were similar for wild-type (WT), OE, and CS plants. However, CS plants and fruits were extremely sensitive to elevated temperatures, because heat stress-induced synthesis of chaperones and Hsfs was strongly reduced or lacking. Despite the complexity of the plant Hsf family with at least 17 members in tomato, HsfA1 has a unique function as master regulator for induced thermotolerance. Using transient reporter assays with mesophyll protoplasts from WT tomato, we demonstrated that plasmid-encoded HsfA1 and HsfA2 were well expressed. However, in CS protoplasts the cosuppression phenomenon was faithfully reproduced. Only transformation with HsfA2 expression plasmid led to normal expression of the transcription factor and reporter gene activation, whereas even high amounts of HsfA1 expression plasmids were silenced. Thermotolerance in CS protoplasts was restored by plasmid-borne HsfA2, resulting in expression of chaperones, thermoprotection of firefly luciferase, and assembly of heat stress granules.
Background: Leaf venation traits are important for many research fields such as systematics and evolutionary biology, plant physiology, climate change, and paleoecology. In spite of an increasing demand for vein trait data, studies are often still data-limited because the development of methods that allow rapid generation of large sets of vein data has lagged behind. Recently, non-destructive X-ray technology has proven useful as an alternative to traditional slow and destructive chemical-based methods. Non-destructive techniques more readily allow the use of herbarium specimens, which provide an invaluable but underexploited resource of vein data and related environmental information. The utility of 2D X-ray technology and microfocus X-ray computed tomography, however, has been compromised by insufficient image resolution. Here, we advanced X-ray technology by increasing image resolution and throughput without the application of contrast agents.
Results: For 2D contact microradiography, we developed a method which allowed us to achieve image resolutions of up to 7 µm, i.e. a 3.6-fold increase compared to the industrial standard (25 µm resolution). Vein tracing was further optimized with our image processing standards that were specifically adjusted for different types of leaf structure and the needs of higher imaging throughput. Based on a test dataset, in 91% of the samples the 7 µm approach led to a significant improvement in estimations of minor vein density compared to the industrial standard. Using microfocus X-ray computed tomography, very high-resolution images were obtained from a virtual 3D–2D transformation process, which was superior to that of 3D images.
Conclusions: Our 2D X-ray method with a significantly improved resolution advances rapid non-destructive bulk scanning at a quality that in many cases is sufficient to determine key venation traits. Together with our high-resolution microfocus X-ray computed tomography method, both non-destructive approaches will help in vein trait data mining from museum collections, which provide an underexploited resource of historical and recent data on environmental and evolutionary change. In spite of the significant increase in effective image resolution, a combination of high-throughput and full visibility of the vein network (including the smallest veins and their connectivity) remains challenging, however.
A balanced sphingolipid rheostat is indispensable for dendritic cell function and survival and thus initiation of an immune response. Sphingolipid levels are dynamically maintained by the action of sphingolipid enzymes of which sphingosine kinases, S1P phosphatases (SGPP-1/2) and S1P lyase (SGPL-1), are pivotal in the balance of S1P and sphingosine levels. In this study, we present that SGPP-1 and SGPL-1 are regulated in inflammatory dendritic cells and contribute to S1P fate. TLR-dependent activation caused SGPL-1 protein downregulation with subsequent decrease of enzymatic activity by two-thirds. In parallel, confocal fluorescence microscopy revealed that endogenous SGPP-1 was expressed in nuclei of naive dendritic cells and was translocated into the cytoplasmatic compartment upon inflammatory stimulation resulting in dephosphorylation of S1P. Mass spectrometric determination showed that a part of the resulting sphingosine was released from the cell, increasing extracellular levels. Another route of diminishing intracellular S1P was possibly taken by its export via ATP-binding cassette transporter C1 which was upregulated in array analysis, while the S1P transporter, spinster homolog 2, was not relevant in dendritic cells. These investigations newly describe the sequential expression and localization of the endogenous S1P regulators SGPP-1 and SGPL-1 and highlight their contribution to the sphingolipid rheostat in inflammation.
Die Wahrscheinlichkeit einer pathologischen Komplettremission (pCR) bei Brustkrebs nach neoadjuvanter Chemotherapie (NACT) nimmt zu; vor allem in den Subgruppen der tripel-negativen und HER-2-positiven Tumoren. Daher stellt sich die Frage, ob bei einer Komplettremission nach NACT eine operative Therapie der Brust notwendig ist, und ob es einen Vorteil für das onkologische Behandlungsergebnis hat, wenn kein Tumor mehr nachgewiesen werden kann. Ein Verzicht auf die Operation und gegebenenfalls auch auf die Radiotherapie ist jedoch nur auf der Basis einer verlässlichen pCR-Diagnose ohne Operation denkbar. Bildgebende Verfahren erreichen derzeit nicht die nötige Sensitivität und Spezifität, um die Diagnose einer pathologischen Komplettremission sicher zu stellen. Daher sind weitere Studien nötig, um herauszufinden, welche Methode die bestmögliche Evaluation des Tumoransprechens auf NACT erlaubt. Erste vielversprechende Ergebnisse zeigen sich in Studien zu bildgebungsgesteuerten, minimalinvasiven Biopsien nach NACT. Diese evaluieren die Möglichkeit einer pCR-Diagnose vor der Operation und könnten die Grundlage für weitere Studien zu einem möglichen Verzicht auf eine Operation in diesem ausgewählten Kollektiv sein.
The likelihood of pathological complete remission (pCR) of breast cancer following neoadjuvant chemotherapy (NACT) is increasing; most of all in the triple negative and HER2 positive tumour subgroups. The question thus arises whether or not breast surgery is necessary when there is complete remission after NACT, and whether it provides any improvement of the oncological treatment result when tumour is no longer detectable. Avoiding surgery and possibly even radiotherapy would only be conceivable on the basis of a reliable diagnosis of pCR without operating. Current imaging does not achieve the necessary sensitivity and specificity to assure the diagnosis of pathological complete remission. Further studies are therefore required to determine which methods are best able to evaluate tumour response to NACT. Studies on image-guided, minimally invasive biopsies after NACT have delivered first promising results towards diagnosing pCR before surgery and could provide the basis for further studies on the possibility of avoiding surgery in this specific patient collective.
Flightless-I governs cell fate by recruiting the SUMO isopeptidase SENP3 to distinct HOX genes
(2017)
Background: Despite recent studies on the role of ubiquitin-related SUMO modifier in cell fate decisions, our understanding on precise molecular mechanisms of these processes is limited. Previously, we established that the SUMO isopeptidase SENP3 regulates chromatin assembly of the MLL1/2 histone methyltransferase complex at distinct HOX genes, including the osteogenic master regulator DLX3. A comprehensive mechanism that regulates SENP3 transcriptional function was not understood.
Results: Here, we identified flightless-I homolog (FLII), a member of the gelsolin family of actin-remodeling proteins, as a novel regulator of SENP3. We demonstrate that FLII is associated with SENP3 and the MLL1/2 complex. We further show that FLII determines SENP3 recruitment and MLL1/2 complex assembly on the DLX3 gene. Consequently, FLII is indispensible for H3K4 methylation and proper loading of active RNA polymerase II at this gene locus. Most importantly, FLII-mediated SENP3 regulation governs osteogenic differentiation of human mesenchymal stem cells.
Conclusion: Altogether, these data reveal a crucial functional interconnection of FLII with the sumoylation machinery that converges on epigenetic regulation and cell fate determination.
I present a new business cycle model in which decision making follows a simple mental process motivated by neuroeconomics. Decision makers first compute the value of two different options and then choose the option that offers the highest value, but with errors. The resulting model is highly tractable and intuitive. A demand function in level replaces the traditional Euler equation. As a result, even liquid consumers can have a large marginal propensity to consume. The interest rate affects consumption through the cost of borrowing and not through intertemporal substitution. I discuss the implications for stimulus policies.
This paper analyses whether the post-crisis regulatory reforms developed by global-standard-setting bodies have created appropriate incentives for different types of market participants to centrally clear Over-The-Counter (OTC) derivative contracts. Beyond documenting the observed facts, we analyze four main drivers for the decision to clear: 1) the liquidity and riskiness of the reference entity; 2) the credit risk of the counterparty; 3) the clearing member’s portfolio net exposure with the Central Counterparty Clearing House (CCP) and 4) post trade transparency. We use confidential European trade repository data on single-name Sovereign Credit Derivative Swap (CDS) transactions, and show that for all the transactions reported in 2016 on Italian, German and French Sovereign CDS 48% were centrally cleared, 42% were not cleared despite being eligible for central clearing, while 9% of the contracts were not clearable because they did not satisfy certain CCP clearing criteria. However, there is a large difference between CCP clearing members that clear about 53% of their transactions and non-clearing members, even those that are subject to counterparty risk capital requirements, that almost never clear their trades. Moreover, we find that diverse factors explain clearing members’ decision to clear different CDS contracts: for Italian CDS, counterparty credit risk exposures matter most for the decision to clear, while for French and German CDS, margin costs are the most important factor for the decision. Clearing members use clearing to reduce their exposures to the CCP and largely clear contracts when at least one of the traders has a high counterparty credit risk.
We have recently shown that caspase-8 is a new substrate of Polo-like kinase 3 (Plk3) that phosphorylates the protein on residue T273 thereby promoting its pro-apoptotic function. In the present study we aimed to investigate the clinical relevance of Plk3 expression and phosphorylation of caspase-8 at T273 in patients with anal squamous cell carcinoma (SSC) treated with 5-fluorouracil and mitomycin C-based chemoradiotherapy (CRT). Immunohistochemical detection of the markers was performed in pretreatment biopsy specimens of 95 patients and was correlated with clinical/histopathologic characteristics including HPV-16 virus load/p16INK4a expression and cumulative incidence of local and distant failure, cancer specific survival (CSS), and overall survival (OS). We observed significant positive correlations between Plk3 expression, pT273 caspase-8 signal, and levels of HPV-16 virus DNA load/p16INK4a detection. Patients with high scores of Plk3 and pT273 caspase-8 showed increased local control (p = 0.011; p = 0.001), increased CSS (p = 0.011; p = 0.013) and OS (p = 0.024; p = 0.001), while the levels of pT273 caspase-8 were significantly associated (p = 0.033) with distant metastases. In multivariate analyses Plk3 expression remained significant for local failure (p = 0.018), CSS (p = 0.016) and OS (p = 0.023). Moreover, a combined HPV16 DNA load and Plk3 or pT273 caspase-8 variable revealed a significant correlation to decreased local failure (p = 0.001; p = 0.009), increased CSS (p = 0.016; p = 0.023) and OS (p = 0.003; p = 0.003). In conclusion these data indicate that elevated levels of Plk3 and pT273 caspase-8 are correlated with favorable clinical outcome in patients with anal SCC treated with concomitant CRT.
Background: Aside from the fully licensed herbal medicines there are products on the European pharmaceutical market which are registered by virtue of their longstanding traditional use. The normal registration procedure does not apply to them because presently they do not meet the legal requirements for a full license as set out in the relevant European Union Directive. One of these requirements, “proof of tradition”, has so far been dealt with in different ways and fails to meet the criteria of good practice.
Method: This analysis is based on a selective literature search in PubMed and in databases of medical and pharmaceutical history, interviews with licensing experts, a consensus meeting attended by researchers with a background in general medicine, phytotherapy, medical and pharmaceutical history, biometry, ethnopharmacology, pharmacognosy and the pharmaceutical industry.
Results and discussion: The 2004 EU Directive, which governs the registration of Traditional Herbal Medicinal Products and demands proof of tradition, is a regulatory construct and, above all, the outcome of a political process that has ended in a pragmatic compromise. The concept of tradition applied in the Directive does not sufficiently reflect the semantic breadth of the term. The only condition defined is that a specific commercial preparation needs to have been on the market for 30 years (15 of them inside the EU). Such an approach does not make full scientific use of the evidence available because the information excerpted from historical sources, if adequately processed, may yield valuable insights. This applies to indications, modes of application, efficacy and product safety (innocuousness). Such criteria should enter in full into the benefit-risk-analysis of applied preparations, in the registration process as well as in the therapeutic practice.
Conclusion: When registering Traditional Herbal Medicinal Products the criterion of evidence-based medicine will only be met if all the facts available are assessed and evaluated, over and above the formally stipulated regulatory provisions (30 years, product reference). To this end, the scientific methods (from among the natural, life or cultural sciences), which are recognized as authoritative in each case, must be applied.
Der Aufsatz vergleicht das barocke Trauerspiel 'Catharina von Georgien' mit der spanischen comédia 'El principe constante' in Hinblick auf ihren Anspruch universaler Geltung und setzt beide von der antiken Tragödie 'Antigone' ab. Besonderes Augenmerk wird dabei der Rolle sprachlicher Ambivalenz sowie der Figur des Gespenstes gewidmet.
The paper presents a reading of "celestinesque literature" - texts surrounding Fernando de Rojas’ famous novel 'La Celestina' (1499) - in view of the question, to what extent the term "marranism" may serve as a philological rather than a biographical category. Dealing with Stephen Gilman’s exemplary studies, the paper shows how Rojas’ text subverts some of the most important metaphorical structures used by philologists to represent "marranism" and to read "marrano literature." Celestinesque novels, on the other hand, develop their own notion of "philology:" the "love" that they narrate also reflects the "desire of the logos" that works throughout their language.
"In der Machination", so Walter Benjamin, "hat die neue Bühne den Gott." Das gilt nicht nur für die Theatermaschinerie, die den Gott auf der Barockbühne erscheinen lässt, sondern ebenso für die weiteren Bedeutungen des Wortes: "Machination" im Sinn des kunstfertigen Verstands und der trügerischen List, wie sie sich in der Intrige, dem dramatischen Kern des Trauerspiels, verkörpert. Der Aufsatz entfaltet den Zusammenhang zwischen Machination und Theophanie in einem Vergleich zwischen den barocken Dichtern Gryphius und Racine. Während die Spiele des Ersteren sich vorrangig auf die anschauliche Wirkung der Maschine stützen, um die Souveränität des 'christlichen' Gesetzes zu demonstrieren, präsentieren sich die Dramen des Letzteren als Musterbeispiele für ingeniöse Handlungsführung im Namen eines Regelwerks, dessen poetologische Autorität als 'göttlich' anerkannt wird. Zwischen diesen beiden Modellen theatralen Spiels vermittelt die Analyse einer Edition der aristotelischen Poetik, die Daniel Heinsius herausgegeben hat und einen besonderen Schwerpunkt auf die Deutung des deus ex machina legt.
Der Aufsatz untersucht am Beispiel des Märtyrerspiels "Catharina von Georgien" die Charakteristik der Gryph'schen Trauerspielsprache zwischen "erhabenem Stil" und sermo humilis. Unter Rückgriff auf die einschlägigen Studien Auerbachs wird besonderes Augenmerk auf das problematische Verhältnis zwischen dem christlichen Gegenstand - der Passion als Erniedrigung des Gottessohnes - und der barocken Stillehre gelegt: Solange das Trauerspiel dem "erhabenen Stil" den Vorzug gibt, kann es das christliche Heilsgeschehen nur verfremdend wiederholen.
With reference to the martyr-play "Catharina von Georgien," my paper examines the rhetorical characteristics of Gryphius' mourning-plays as a movement between "elevated style" and sermo humilis. Drawing upon Auerbach's important studies on this subject, it highlights the problematic relationship between the play's Christian subject - the passion as humiliation of the divine Son - and baroque notions of (stylistic) elevation: As long as the mourning-play gives preference to "elevated style," it can only restage Christian salvation through its distortion.