744 research outputs found

    Kompetenzorientierte Lehrveranstaltungsevaluation an Musikhochschulen

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    Ensembleunterricht an Musikhochschulen kann mit bestehenden Evaluationsinstrumenten nur unzureichend evaluiert werden. Der Beitrag zeigt, wie ein fragebogenbasiertes Instrument zur Evaluation von Ensembleunterricht entwickelt wurde, das den Lehrenden die Reflexion ihres Unterrichts vor dem Hintergrund der Lernziele ermöglicht. Hierbei konnten auf Basis einer qualitativen Lehrendenbefragung ein differenzierter Katalog von Kompetenzen identifiziert werden, der ausschnittweise präsentiert wird. Das Instrument bietet damit Anknüpfungspunkte zu Hochschuldidaktik und Curriculumsentwicklung. 13.10.2017 | Melanie Franz-Özdemir & Frederic Neu

    Renal developmental genes are differentially regulated after unilateral ureteral obstruction in neonatal and adult mice

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    Congenital obstructive nephropathy hinders normal kidney development. The severity and the duration of obstruction determine the compensatory growth of the contralateral, intact opposite kidney. We investigated the regulation of renal developmental genes, that are relevant in congenital anomalies of the kidney and urinary tract (CAKUT) in obstructed and contralateral (intact opposite) kidneys after unilateral ureteral obstruction (UUO) in neonatal and adult mice. Newborn and adult mice were subjected to complete UUO or sham-operation, and were sacrificed 1, 5, 12 and 19 days later. Quantitative RT-PCR was performed in obstructed, intact opposite kidneys and sham controls for Gdnf, Pax2, Six4, Six2, Dach1, Eya1, Bmp4, and Hnf-1 beta. Neonatal UUO induced an early and strong upregulation of all genes. In contrast, adult UUO kidneys showed a delayed and less pronounced upregulation. Intact opposite kidneys of neonatal mice revealed a strong upregulation of all developmental genes, whereas intact opposite kidneys of adult mice demonstrated only a weak response. Only neonatal mice exhibited an increase in BMP4 protein expression whereas adult kidneys strongly upregulated phosphatidylinositol 3 kinase class III, essential for compensatory hypertrophy. In conclusion, gene regulation differs in neonatal and adult mice with UUO. Repair and compensatory hypertrophy involve different genetic programs in developing and adult obstructed kidneys

    Biokinetics and dosimetry of 111In-DOTA-NOC-ATE compared with 111In-DTPA-octreotide

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    Purpose: The biokinetics and dosimetry of 111In-DOTA-NOC-ATE (NOCATE), a high-affinity ligand of SSTR-2 and SSTR-5, and 111In-DTPA-octreotide (Octreoscan™, OCTREO) were compared in the same patients. Methods: Seventeen patients (10 men, 7 women; mean age 60years), referred for an OCTREO scan for imaging of a neuroendocrine tumour (15), thymoma (1) or medullary thyroid carcinoma (1), agreed to undergo a second study with NOCATE. Whole-body anterior-posterior scans were recorded 0.5 (100% reference scan), 4, 24 and 48h (17 patients) and 120h (5 patients) after injection. In 16 patients the OCTREO scan (178 ± 15MBq) was performed 16 ± 5days before the NOCATE scan (108 ± 14MBq) with identical timing; 1 patient had the NOCATE scan before the OCTREO scan. Blood samples were obtained from 14 patients 5min to 48h after injection. Activities expressed as percent of the initial (reference) activity in the whole body, lung, kidney, liver, spleen and blood were fitted to biexponential or single exponential functions. Dosimetry was performed using OLINDA/EXM. Results: Initial whole-body, lung and kidney activities were similar, but retention of NOCATE was higher than that of OCTREO. Liver and spleen uptakes of NOCATE were higher from the start (p < 0.001) and remained so over time. Whole-body activity showed similar α and β half-lives, but the β fraction of NOCATE was double that of OCTREO. Blood T 1/2β for NOCATE was longer (19 vs. 6h). As a result, the effective dose of NOCATE (105μSv/MBq) exceeded that of OCTREO (52μSv/MBq), and the latter result was similar to the ICRP 106 value of 54μSv/MBq. Differential activity measurement in blood cells and plasma showed an average of <5% of NOCATE and OCTREO attached to globular blood components. Conclusion: NOCATE showed a slower clearance from normal tissues and its effective dose was roughly double that of OCTRE

    Life stage-specific hydropeaking flow rules

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    ReviewPeak-operating hydropower plants are usually the energy grid’s backbone by providing flexible energy production. At the same time, hydropeaking operations are considered one of the most adverse impacts on rivers, whereby aquatic organisms and their life-history stages can be affected in many ways. Therefore, we propose specific seasonal regulations to protect ecologically sensitive life cycle stages. By reviewing hydropeaking literature, we establish a framework for hydrological mitigation based on life-history stages of salmonid fish and their relationship with key parameters of the hydrograph. During migration and spawning, flows should be kept relatively stable, and a flow cap should be implemented to prevent the dewatering of spawning grounds during intragravel life stages. While eggs may be comparably tolerant to dewatering, post-hatch stages are very vulnerable, which calls for minimizing or eliminating the duration of drawdown situations and providing adequate minimum flows. Especially emerging fry are extremely sensitive to flow fluctuations. As fish then grow in size, they become less vulnerable. Therefore, an ‘emergence window’, where stringent thresholds on ramping rates are enforced, is proposed. Furthermore, time of day, morphology, and temperature changes must be considered as they may interact with hydropeaking. We conclude that the presented mitigation framework can aid the environmental enhancement of hydropeaking rivers while maintaining flexible energy productioninfo:eu-repo/semantics/publishedVersio

    Identifying components required for OMP biogenesis as novel targets for antiinfective drugs

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    The emergence of multiresistant Gram-negative bacteria requires new therapies for combating bacterial infections. Targeting the biogenesis of virulence factors could be an alternative strategy instead of killing bacteria with antibiotics. The outer membrane (OM) of Gram-negative bacteria acts as a physical barrier. At the same time it facilitates the exchange of molecules and harbors a multitude of proteins associated with virulence. In order to insert proteins into the OM, an essential oligomeric membrane-associated protein complex, the ss-barrel assembly machinery (BAM) is required. Being essential for the biogenesis of outer membrane proteins (OMPs) the BAM and also periplasmic chaperones may serve as attractive targets to develop novel antiinfective agents. Herein, we aimed to elucidate which proteins belonging to the OMP biogenesis machinery have the most important function in granting bacterial fitness, OM barrier function, facilitating biogenesis of dedicated virulence factors and determination of overall virulence. To this end we used the enteropathogen Yersinia enterocolitica as a model system. We individually knocked out all non-essential components of the BAM (BamB, C and E) as well as the periplasmic chaperones DegP, SurA and Skp. In summary, we found that the most profound phenotypes were produced by the loss of BamB or SurA with both knockouts resulting in significant attenuation or even avirulence of Ye in a mouse infection model. Thus, we assume that both BamB and SurA are promising targets for the development of new antiinfective drugs in the future.Peer reviewe

    Effects of HIF-1 inhibition by chetomin on hypoxia-related transcription and radiosensitivity in HT 1080 human fibrosarcoma cells

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    <p>Abstract</p> <p>Background</p> <p>Hypoxia-inducible factor-1 (HIF-1) overexpression has been linked to tumor progression and poor prognosis. We investigated whether targeting of HIF-1 using chetomin, a disrupter of the interaction of HIF-1 with the transcriptional coactivator p300, influences the radiosensitivity of hypoxic HT 1080 human fibrosarcoma cells.</p> <p>Methods</p> <p>Optimal dose of chetomin was determined by EGFP-HRE gene reporter assay in stably transfected HT 1080 cells. Cells were assayed for expression of the hypoxia-inducible genes carbonic anhydrase 9 (CA9) and vascular endothelial growth factor (VEGF) by RT-PCR and for clonogenic survival after irradiation with 2, 5 or 10 Gy, under normoxic or hypoxic (0.1% O<sub>2</sub>, 12 h) conditions in the presence or absence of chetomin (150 nM, 12 h, pre-treatment of 4 h).</p> <p>Results</p> <p>Chetomin treatment significantly reduced CA9 and VEGF mRNA expression in hypoxic cells to 44.4 ± 7.2% and 39.6 ± 16.0%, respectively, of untreated hypoxic controls. Chetomin clearly reduced the modified oxygen enhancement ratio (OER') compared to untreated cells, from 2.02 to 1.27, from 1.86 to 1.22 and from 1.49 to 1.06 at the 50%, 37% and 10% clonogenic survival levels, respectively.</p> <p>Conclusion</p> <p>HIF-1 inhibition by chetomin effectively reduces hypoxia-dependent transcription and radiosensitizes hypoxic HT 1080 human fibrosarcoma cells <it>in vitro</it>.</p

    Environmental change during MIS4 and MIS 3 opened corridors in the Horn of Africa for <i>Homo sapiens</i> expansion

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    Archaeological findings, numerical human dispersal models and genome analyses suggest several time windows in the past 200 kyr (thousands of years ago) when anatomically modern humans (AMH) dispersed out of Africa into the Levant and/or Arabia. From close to the key hominin site of Omo-Kibish, we provide near continuous proxy evidence for environmental changes in lake sediment cores from the Chew Bahir basin, south Ethiopia. The data show highly variable hydroclimate conditions from 116 to 66 kyr BP with rapid shifts from very wet to extreme aridity. The wet phases coincide with the timing of the North African Humid Periods during MIS5, as defined by Nile discharge records from the eastern Mediterranean. The subsequent record at Chew Bahir suggests stable regional hydrological setting between 58 and 32 kyr (MIS4 and 3), which facilitated the development of more habitable ecosystems, albeit in generally dry climatic conditions. This shift, from more to less variable hydroclimate, may help account for the timing of later dispersal events of AMH out of Africa

    Injectable living marrow stromal cell-based autologous tissue engineered heart valves: first experiences with a one-step intervention in primates

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    Aims A living heart valve with regeneration capacity based on autologous cells and minimally invasive implantation technology would represent a substantial improvement upon contemporary heart valve prostheses. This study investigates the feasibility of injectable, marrow stromal cell-based, autologous, living tissue engineered heart valves (TEHV) generated and implanted in a one-step intervention in non-human primates. Methods and results Trileaflet heart valves were fabricated from non-woven biodegradable synthetic composite scaffolds and integrated into self-expanding nitinol stents. During the same intervention autologous bone marrow-derived mononuclear cells were harvested, seeded onto the scaffold matrix, and implanted transapically as pulmonary valve replacements into non-human primates (n = 6). The transapical implantations were successful in all animals and the overall procedure time from cell harvest to TEHV implantation was 118 ± 17 min. In vivo functionality assessed by echocardiography revealed preserved valvular structures and adequate functionality up to 4 weeks post implantation. Substantial cellular remodelling and in-growth into the scaffold materials resulted in layered, endothelialized tissues as visualized by histology and immunohistochemistry. Biomechanical analysis showed non-linear stress-strain curves of the leaflets, indicating replacement of the initial biodegradable matrix by living tissue. Conclusion Here, we provide a novel concept demonstrating that heart valve tissue engineering based on a minimally invasive technique for both cell harvest and valve delivery as a one-step intervention is feasible in non-human primates. This innovative approach may overcome the limitations of contemporary surgical and interventional bioprosthetic heart valve prosthese
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