31 research outputs found

    SchĂŒler:innenfragen als Reflexionsstelle fĂŒr fachliches Lernen im Sachunterricht?

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    Reflexion gilt in sachunterrichtsdidaktischen Kontexten als eine Kernkompetenz fachlichen Lernens (GDSU 2013). Dabei kann die SchĂŒler:innenfrage im Sinne Deweys (1910 & 2018) als Umschlagstelle im Denkprozess und Reflexionsstelle fachlichen Lernens verstanden werden. Das Potenzial der Reflexion in der Fragenbearbeitung wird im Beitrag anhand einer Beobachtungsprotokollsequenz exemplarisch analysiert, die im Rahmen des Forschungsprojekts FriSa (Fragen im inklusionsorientierten Sachunterricht) entstanden ist. Hierzu werden aus bestehenden Kriterienkatalogen abgeleitete Indikatoren hinzugezogen, die auf ReflexivitĂ€t in der Fragenbearbeitung hinweisen. (DIPF/Orig.

    The experimental power of FR900359 to study Gq-regulated biological processes.

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    Despite the discovery of heterotrimeric αÎČÎł G proteins ∌25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq

    A Cell-Permeable Inhibitor to Trap Gαq Proteins in the Empty Pocket Conformation

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    In spite of the crucial role of heterotrimeric G proteins as molecular switches transmitting signals from G protein-coupled receptors, their selective manipulation with small molecule, cell-permeable inhibitors still remains an unmet challenge. Here, we report that the small molecule BIM-46187, previously classified as pan-G protein inhibitor, preferentially silences Gαq signaling in a cellular context-dependent manner. Investigations into its mode of action reveal that BIM traps Gαq in the empty pocket conformation by permitting GDP exit but interdicting GTP entry, a molecular mechanism not yet assigned to any other small molecule Gα inhibitor to date. Our data show that Gα proteins may be “frozen” pharmacologically in an intermediate conformation along their activation pathway and propose a pharmacological strategy to specifically silence Gα subclasses with cell-permeable inhibitors

    Prostaglandin D2-supplemented “functional eicosanoid testing and typing” assay with peripheral blood leukocytes as a new tool in the diagnosis of systemic mast cell activation disease: an explorative diagnostic study

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    Background: Systemic mast cell activation disease (MCAD) is characterized by an enhanced release of mast cell-derived mediators, including eicosanoids, which induce a broad spectrum of clinical symptoms. Accordingly, the diagnostic algorithm of MCAD presupposes the proof of increased mast cell mediator release, but only a few mediators are currently established as routine laboratory parameters. We thus initiated an explorative study to evaluate in vitro typing of individual eicosanoid pattern of peripheral blood leukocytes (PBLs) as a new diagnostic tool in MCAD. Methods: Using the “functional eicosanoid testing and typing” (FET) assay, we investigated the balance (i.e. the complex pattern of formation, release and mutual interaction) of prostaglandin E2 (PGE2) and peptido-leukotrienes (pLT) release from PBLs of 22 MCAD patients and 20 healthy individuals. FET algorithms thereby consider both basal and arachidonic acid (AA)-, acetylsalicylic acid (ASA)-, and substance P (SP)-triggered release of PGE2 and pLT. The FET assay was further supplemented by analyzing prostaglandin D2 (PGD2), as mast cell-specific eicosanoid. Results: We observed marked PGE2-pLT imbalances for PBLs of MCAD patients, as indicated by a markedly enhanced mean FET value of 1.75 ± 0.356 (range: 1.14–2.36), compared to 0.53 ± 0.119 (range: 0.36-0.75) for healthy individuals. In addition, mean PGD2 release from PBLs of MCAD patients was significantly, 6.6-fold higher than from PBLs of healthy individuals (946 ± 302.2 pg/ml versus 142 ± 47.8 pg/ml; P < 0.001). In contrast to healthy individuals, PGD2 release from PBLs of MCAD patients was markedly triggered by SP (mean: 1896 ± 389.7 pg/ml; P < 0.001), whereas AA and ASA caused individually varying effects on both PGD2 and pLT release. Conclusions: The new in-vitro FET assay, supplemented with analysis of PGD2, demonstrated that the individual patterns of eicosanoid release from PBLs can unambiguously distinguish MCAD patients from healthy individuals. Notably, in our analyses, the FET value and both basal and triggered PGD2 levels were not significantly affected by MCAD-specific medication. Thus, this approach may serve as an in-vitro diagnostic tool to estimate mast cell activity and to support individualized therapeutic decision processes for patients suffering from MCAD

    Phase 3, Randomized, 20-Month Study of the Efficacy and Safety of Bimatoprost Implant in Patients with Open-Angle Glaucoma and Ocular Hypertension (ARTEMIS 2)

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    Objective- To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 ”g bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods- This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 ”g bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD). Results- Both 10 and 15 ”g bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2–7.4, 6.5–7.8, and 6.1–6.7 mmHg through week 12 in the 10 ”g implant, 15 ”g implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 ”g implant) and 79.0% (15 ”g implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 ”g implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 ”g implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 ”g implant group compared with the timolol group. Conclusions- The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 ”g implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma

    HandlungsSpielRĂ€ume. Selbstwirksamkeit von Kindern im Übergang von der Kindertageseinrichtung in die Grundschule

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    Velten K. HandlungsSpielRĂ€ume. Selbstwirksamkeit von Kindern im Übergang von der Kindertageseinrichtung in die Grundschule. Empirische Forschung im Elementar- und Primarbereich. Vol 7. Bad Heilbrunn: Julius Klinkhardt; 2020

    Self-efficacy experiences in day care and primary school from the children's perspective: A starting point for the reflection of didactic and methodological competences of adult educators

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    Velten K. Self-efficacy experiences in day care and primary school from the children's perspective: A starting point for the reflection of didactic and methodological competences of adult educators. Journal of Early Childhood Research. 2021: 1476718X211051192.This paper discusses self-efficacy as a key factor in children managing the transition to primary school, the threshold to formal education and further learning processes. In presenting results of a qualitative-longitudinal interview study of German preschool and primary school children's perspectives on their self-efficacy experiences, it furnishes evidence for enhancing self-efficacy in pedagogical practice in a so-called mastery climate. Co-determined or self-determined opportunities for playing without adult intervention prove to be central in this to children's self-efficacy. Following on from this, the discussion will make references to the pedagogical relevance of child-led or unsupervised play for the promotion of self-efficacy in both settings. In addition, based on the reflection of the concept of generational order, the study points to concrete starting points to focus on necessary didactic and methodological competences of adult educators for the appropriate design of child-oriented co-determined or self-determined learning settings

    KinderstÀrkende PÀdagogik und Didaktik in der Grundschule

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    Miller S, Velten K. KinderstÀrkende PÀdagogik und Didaktik in der Grundschule. KinderStÀrken. Vol 6. Stuttgart: Kohlhammer; 2015

    Partizipative Forschung mit Kindern im internationalen Diskurs – Impulse fĂŒr die Grundschulforschung in Deutschland

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    HĂŒpping B, Velten K. Partizipative Forschung mit Kindern im internationalen Diskurs – Impulse fĂŒr die Grundschulforschung in Deutschland. Zeitschrift fĂŒr Grundschulforschung. 2022.Partizipative Forschung mit Kindern gewinnt im Schnittfeld von Kindheits- und Grundschulforschung national und international an Bedeutung, um Kinder und ihre Perspektiven in Forschungsprojekte einzubeziehen. Ergebnisse eines systematischen Forschungsreviews zur Partizipativen Forschung mit Grundschulkindern zeigen, dass in englischsprachigen Studien forschungsethische Fragen systematischer im Forschungsprozess mit den Kindern und als zentraler Gegenstand in Publikationen reflektiert werden, wĂ€hrend deutschsprachige Studien vor allem AnsĂ€tze Partizipativer Forschung forschungsmethodisch diskutieren und Fragen generationaler Ordnung und (Macht)Asymmetrien eher im Diskursfeld der Erwachsenen verbleiben. Daraus werden Herausforderungen sowie Potenziale fĂŒr die Grundschulforschung in Deutschland abgeleitet.Participatory research with children is gaining national and international importance in the intersection of childhood and primary school research in order to include children and their perspectives in research projects. Results of a systematic research review on participatory research with primary school children show that in English-language studies research ethics issues are reflected more systematically in the research process, with the children and as a central object in publications, while German-language studies mainly discuss participatory research approaches in terms of research methodology and questions of generational order and (power)asymmetries tend to remain in the field of adult discourse. Challenges and potentials for primary school research in Germany are derived from this

    Participatory and inclusive research? Ethical reflexions about interviews with children with particular reference to adulthood

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    Velten K, Höke J. Forschung partizipativ und inklusiv gestalten? Ethische Reflexionen zu Interviews mit Kindern unter besonderer BerĂŒcksichtigung von Erwachsenheit. Zeitschrift fĂŒr Grundschulforschung. 2021;14(2):421-436.**Zusammenfassung** Im Beitrag wird mit Fokus auf vier AnsprĂŒche an die Erfassung von Kinderperspektiven der methodische Zugang des Interviews daraufhin reflektiert, wie im Kontext von kindlichem Eigensinn und generationaler Ordnung die Erwachsenheit der Forscher*innen aus forschungsethischer Sicht betrachtet werden kann und muss. In der sequenzanalytischen Re-Analyse von konflikthaften und weniger ergiebig erscheinenden Interviewsequenzen werden sog. Ad-hoc-Praktiken deutlich, in denen Forscher*innen in der Einmaligkeit der konkreten Interviewsituation Erwachsenheit und generationale Ordnung bei gleichzeitigem Interesse am Eigensinn des Kindes (re)produzieren. Diese sog. „Turning Points“ bieten Impulse fĂŒr die Justierung des Begriffs der Angemessenheit und die Erweiterung von individuellen Forschungskompetenzen bei Kinderbefragungen.**Abstract** In the paper, the methodological approach of the interview is reflected upon, with a focus on four demands on the recording of children’s perspectives, how the researchers’ adulthood can and must be considered from a research ethical point of view in the context of childlike attachments and generational order. In the sequence re-analysis of conflictual and less productive interview sequences, so-called ad hoc practices are particularly evident in which researchers (re)produce adulthood and generational order in the uniqueness of the concrete interview situation despite parallel interest in the child’s obstinacy. These so-called “turning points” offer impulses for the adjustment of the concept of appropriateness and the expansion of individual research competences in child interviews
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