Gemcitabine therapeutically disrupts essential SIRT1-mediated p53 repression in atypical teratoid/rhabdoid tumors

Atypical teratoid/rhabdoid tumors (ATRTs) are highly malignant embryonal tumors of the central nervous system with a dismal prognosis. Using a newly developed and validated patient-derived ATRT culture and xenograft model, alongside a panel of primary ATRT models, we found that ATRTs are selectively sensitive to the nucleoside analog gemcitabine. Gene expression and protein analyses indicate that gemcitabine treatment causes the degradation of sirtuin 1 (SIRT1), resulting in cell death through activation of nuclear factor κB (NF-κB) and p53. Furthermore, we discovered that gemcitabine-induced loss of SIRT1 results in a nucleus-to-cytoplasm translocation of the sonic hedgehog (SHH) signaling activator GLI2, explaining the observed additional gemcitabine sensitivity in SHH-subtype ATRT. Treatment of ATRT xenograft-bearing mice with gemcitabine resulted in a &gt;30% increase in median survival and yielded long-term survivors in two independent patient-derived xenograft models. These findings demonstrate that ATRTs are highly sensitive to gemcitabine treatment and may form part of a future multimodal treatment strategy for ATRTs.</p

Analysis of initial stabilization of cell efficiency in amorphous silicon photovoltaic modules under real outdoor conditions

[EN] This contribution presents a field study in which the initial stabilization of thin-film amorphous silicon (a-Si:H) is investigated. Two grid-connected a-Si:H photovoltaic plants have been monitored and analyzed under real outdoor conditions. A per-unit approach is proposed to compare PV plants with differences in their electrical characteristic and the start-up date. The representation of a normalized per unit PV power versus the accumulated incoming irradiation reveals an evolution that can be characterized through an exposure-response function. By this function, two populations of defects in the cells are detected. It is found that the stabilization process in the first year of operation produces a decrease of 10% in the peak power, equivalent to a decrease of 0.5% in cell efficiency. The use of the accumulated PSH for conducting the analysis of the initial stabilization produces similarities that cannot be obtained if a time scale is used. These results provide a powerful tool for PV plant designers because they enable a prediction to be made of the time-scale stabilization response in terms of unitary power, correlated with the peak sun hours received. (C) 2017 Elsevier Ltd. All rights reserved.This work was supported by Generalitat Valenciana (PROM-ETEOII/2014/059) and Spanish MINECO (Ministry of Economy and Competitiveness TEC2014-53727-C2-1-R).Mateo-Guerrero, C.; Hernández Fenollosa, MDLÁ.; Montero Reguera, ÁE.; Segui-Chilet, S. (2018). Analysis of initial stabilization of cell efficiency in amorphous silicon photovoltaic modules under real outdoor conditions. Renewable Energy. 120:114-125. https://doi.org/10.1016/j.renene.2017.12.054S11412512

Handlungskompetenzorientiertes Lehren und Prüfen am Beispiel der Arbeitsunterweisung „Kommunikationstraining“

Im Rahmen dieser Bachelorthesis soll ein Leitfaden für das kompetenz- und handlungsorientierte Lehren und Prüfen erstellt werden. Am Beispiel der Arbeitsunterweisung des „Kommunikationstrainings“ soll verdeutlicht werden, wodurch sich eine Handlungs- und Kompetenzorientierung sowohl in Lehrveranstaltungen, als auch in Prüfungen auszeichnet. Dazu wird zunächst die Theorie, die zur Entstehung der Handlungs- und Kompetenzorientierung in den Vorlesungen und Lehrveranstaltungen geführt haben, umrissen und in einen geschichtlichen Rahmen eingeordnet. Besonders beleuchtet wird dabei die internationale Leistungsmessung von Bildungsstandards; das sogenannte Bildungsmonitoring. Der zweite Teil dieser Thesis gibt einen Überblick über die Definitionen von Kompetenzen und Handlungskompetenzen in schulischer, beruflicher und hochschulischer Bildung. Die Ansätze werden einander gegenübergestellt und Unterschiede und Gemeinsamkeiten herausgestellt. Im dritten Teil der Arbeit wird die Theorie mit der Praxis verknüpft und die Handlungs- und Kompetenzorientierung anhand von Beispielen in konkrete Lehr- und Lernsituationen übertragen. Die hier entwickelten Prüfungsfragen und Lösungen werden auf ihren Kompetenzgehalt und ihre Handlungsorientierung hin untersucht und analysiert

Duchenne muscular dystrophy : a genetic, cognitive and psychosocial approach

Duchenne muscular dystrophy (DMD) is a severe, progressive muscle wasting disorder that affects 1 in 3600 male births. It is caused by genetic mutations in the dystrophin gene. This study investigated several aspects of the neuromuscular disorder within a population of Brazilian DMD boys and their families. This study's framework was laid out within the prism of an interacting cycle of genetic factors, cognitive functioning, and psychosocial aspects that underlie the neuromuscular disorder. It focuses on DMD's aetiology, history and previous research on genetic, cognitive and psychosocial aspects. Mixed methods were adopted to allow for a more encompassing view of the neuromuscular disorder: cognitive tests, an emotion recognition battery, genetic analyses, well-being questionnaires, and interviews were applied. Correspondent, quantitative and qualitative data analysis was carried out. The findings of 32 DMD patients (mean age 10.4 years, SD= 2 years) and 31 control subjects (mean age 9.4 years, SD= 3 years) revealed severe cognitive dysfunctioning in all assessed cognitive domains in the DMD population, as well as in the ability of emotion recognition. In the DMD group, it could be shown that poor executive functioning stood in a positive correlation with a poor ability of emotion recognition. The DMD patients' cognitive phenotypes were correlated with the genetic mutations in their dystrophin gene, but no relationship between the patients' genotype and cognitive phenotype could be confirmed. These results were contrary to previous research, which suggested that specific mutations in the dystrophin gene cause cognitive impairment. The DMD group scored poorly on the emotion recognition task, which is also a characteristic of autism spectrum disorder. However, when diagnosing for autistic characteristics through means of an interview, only a few similarities between the two disorders could be found. In order to assess the psychosocial components that come along with the disorder, well-being questionnaires were supplied. Interestingly, DMD boys scored higher on well-being than the boys in the control group. Moreover, 30 of the DMD caregivers (mean age app. 31 years) also revealed high levels of well-being, which correlated positively with the well-being of their sons, suggesting high levels of resilience. Given the participants' socio-economic hardship and the lack of governmental help, it was concluded that participants showed an incredible level of resilience that most likely resided within their faith, which nearly all of them stated to be the reason for their strength to strive. The relevant and new information about cognitive, genetic and social aspects of DMD uncovered in this study will pave the way for further (and much needed) studies into psychosocial aspects of the disorder

Characterization of crystalline silicon solar cells under realistic operating conditions

This work presents the characterization of crystalline silicon solar cells under realistic operating conditions, which exceed the conventional standard test conditions (STC). The focus is set on the temperature and the angle of incidence dependence. Highly accurate measurements of the electric performance of silicon solar cells are compared to state-of-the-art numerical device simulations, covering a large range of industrially relevant cell concepts

Temperature-dependent modeling of silicon solar cells - Eg, ni, recombination, and VOC

The characterization and modeling of silicon solar cells under nonstandard conditions is an essential task in order to predict and optimize the annual yield when installed in the field. In this paper, focus is set on the temperature dependence of fundamental physical models for numerical device simulation of silicon solar cells. A wide range of industrially relevant solar cell concepts is simulated and compared to experimental data. The influence of fundamental physical models on the temperature dependence of the simulated devices is investigated. It is found that our simulations are in good agreement with experimental results for silicon solar cells that are limited by extrinsic defect or surface recombination. This is not the case for solar cells featuring carrier-selective contacts where intrinsic recombination processes, such as Auger recombination and radiative recombination, have a significant influence

Angle dependence of solar cells and modules: The role of cell texturization

The angle-dependent spectral response is measured for six differently textured silicon solar cells before and after encapsulation. Deviations from Lambert's cosine law and differences due to the textures can be clearly determined by means of an uncertainty analysis. This effort in highly accurate angle-dependent measurement is needed for reliable prediction of annual performance. Energy rating using common simulation models for three different climate zones shows differences of more than 1% in yearly energy yield solely due to the different angle-dependent behavior of the textures. Modules featuring solar cells with random upright pyramids exhibit the largest angular losses of the studied textures