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Shakhova O.,University of Zurich | Cheng P.,University of Zurich | Mishra P.J.,U.S. National Cancer Institute | Zingg D.,University of Zurich | And 16 more authors.
PLoS Genetics | Year: 2015

Melanoma is the most fatal skin cancer, but the etiology of this devastating disease is still poorly understood. Recently, the transcription factor Sox10 has been shown to promote both melanoma initiation and progression. Reducing SOX10 expression levels in human melanoma cells and in a genetic melanoma mouse model, efficiently abolishes tumorigenesis by inducing cell cycle exit and apoptosis. Here, we show that this anti-tumorigenic effect functionally involves SOX9, a factor related to SOX10 and upregulated in melanoma cells upon loss of SOX10. Unlike SOX10, SOX9 is not required for normal melanocyte stem cell function, the formation of hyperplastic lesions, and melanoma initiation. To the contrary, SOX9 overexpression results in cell cycle arrest, apoptosis, and a gene expression profile shared by melanoma cells with reduced SOX10 expression. Moreover, SOX9 binds to the SOX10 promoter and induces downregulation of SOX10 expression, revealing a feedback loop reinforcing the SOX10 low/SOX9 high ant,m/ii-tumorigenic program. Finally, SOX9 is required in vitro and in vivo for the anti-tumorigenic effect achieved by reducing SOX10 expression. Thus, SOX10 and SOX9 are functionally antagonistic regulators of melanoma development. © 2015, Public Library of Science. All Rights Reserved. Source


Naber C.,University of Erlangen Nuernberg | Goetz-Neunhoeffer F.,University of Erlangen Nuernberg | Gobbels M.,University of Erlangen Nuernberg | Rossler C.,Bauhaus University Weimar | Neubauer J.,University of Erlangen Nuernberg
Cement and Concrete Research | Year: 2016

Alite (Ca3SiO5/C3S with low concentrations of foreign ions) is the main constituent of Ordinary Portland Cement. Normally it forms during sintering but with quite low crystal sizes (ca. 30 μm). For experiments on alite hydration behavior monocrystalline grains are required. Due to its incongruent melting behavior and its thermodynamic instability below 1250 °C it is very challenging to obtain large alite single crystals. In the present study, the floating zone method was used for annealing polycrystalline rods of monoclinic and triclinic C3S just below the melting point of the phase. Large monocrystalline grains (> 500 μm) of the monoclinic (Al, Mg-doped) and triclinic polymorphs could successfully be obtained. Monocrystallinity was demonstrated by electron backscatter diffraction (EBSD). The chemical composition regarding incorporation of foreign ions and thus the resulting crystallographic modification of the C3S can easily be adjusted. Chemical homogeneity of the synthesized monocrystalline grains was proven by electron probe microanalysis (EPMA). © 2016 Elsevier Ltd. All rights reserved. Source


Fifka M.S.,Institute of Business Administration | Kuhn A.-L.,University of Erlangen Nuernberg | Loza Adaui C.R.,Institute of Business Administration | Stiglbauer M.,University of Erlangen Nuernberg
Voluntas | Year: 2016

Non-governmental organizations (NGOs) are a major institutional force in promoting sustainable development, especially in institutional environments where governments have often not been able to assume the role of development agent. Despite this importance, the approach of Latin American NGOs to sustainability has received only little attention so far and respective research is scarce. To address this research gap, we conducted an online survey of 306 Latin American NGOs, investigating their understanding of sustainability and how they seek to transmit it. Due to the lack of previous empirical studies, our study is exploratory in nature and examines eight research categories: (1) NGOs definition of sustainability; (2) the role they see for themselves in its promotion, (3) dimensions of sustainability judged as important, (4) stakeholders and (5) partners considered, (6) motives for pursuing sustainability, (7) forms of implementation, and (8) measures regarded as necessary for spreading it further. Our findings are discussed against the institutional environment of Latin America, as we assume that the understanding and transmission of sustainability is contextual in nature. Our study shows that the sustainability concept of the sample NGOs is broad and that they take a wide variety of efforts for implementing it. Exploratory and confirmatory factor analyses confirmed the reliability and validity of the eight-component-model we applied for our study. Thus, it serves as a valuable starting point for future research into the “terra incognita” of Latin American NGOs’ approach to sustainability. © 2016 International Society for Third-Sector Research and The Johns Hopkins University Source


Klaus S.R.,University of Erlangen Nuernberg | Neubauer J.,University of Erlangen Nuernberg | Goetz-Neunhoeffer F.,University of Erlangen Nuernberg
Cement and Concrete Research | Year: 2015

It is shown that the hydration degree of CA is directly dependent on the fineness of CA-particles. Finer particles lead to an increased degree of hydration and also an increased hydration rate. The reaction of a sample with mainly coarse particles of CA (d50 = 50 μm) is characterized by a low hydration rate and only 34 rel.-% of CA dissolved after 22 h. Whereas in a very fine CA-sample (d50 = 4 μm) hydration starts delayed but then shows the highest hydration rate and a dissolution of 62 rel.-% CA. The behaviour is explained by the coverage of CA-particles with a dense hydrate layer of C2AHx and AHx. This reacted CA-rim is supposed to have the same thickness for different sized CA-particles. Optimization of Gauss distribution curves, which were applied to simulate a more realistic particle size distribution, leads to a reacted rim thickness of 1.3 μm until reaction is stopped. © 2014 Elsevier Ltd. Source


Ectors D.,University of Erlangen Nuernberg | Goetz-Neunhoeffer F.,University of Erlangen Nuernberg | Neubauer J.,University of Erlangen Nuernberg
Journal of Applied Crystallography | Year: 2015

An efficient geometric approach to refine anisotropic domain morphology in the double-Voigt approach based on the variance-slope apparent crystallite size was recently described. In this way, the Lorentzian part of the Voigt size contribution can be directly linked to an effective area-or surface-weighted morphology. The size contribution in the Voigt approach is, however, rarely pure Lorentzian. In this article, the previously considered models are extended for the Gaussian part of the size broadening, also taking into account size distributions. The limits of the validity of the Voigt approach are also discussed. © 2015 International Union of Crystallography. Source

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