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Five bituminous samples were carefully studied by confocal laser scanning microscopy using 488 nm excitation radiation and observing 500-530 nm of emission. The images revealed the microstructure of bitumen. The influence of the admixture of mineral aggregates concerning the microstructure was tested. For the minerals, no significant influence was found. For understanding the origin of fluorescent signals, the samples were separated into asphaltenes and maltenes and analyzed with fluorescence spectroscopy. Although former works have assumed the origin of fluorescent emissions in bitumen to be found in the asphaltene fraction, the asphaltenes produce little to no emissions, but the maltenes exhibit strong fluorescence in the observed spectral region. For deeper insight, fractionation of the bitumina into the SARA fractions by chromatographic column separation was necessary. The fluorescence spectra of these fractions were analyzed and revealed the aromatics and resin phases to be the only components capable of sufficiently intense fluorescent emission. This is a strong argument for a complex internal microstructure consisting of a mantle of aromatics surrounding an inner core. [ABSTRACT FROM AUTHOR]

The description of the mechanical behavior of bitumen on the basis of its microstructure allows its improvement and moreover the development of equivalent or even more sustainable materials with similar properties. For this reasons, a micromechanical model for bitumen is proposed, allowing the description of the viscoelastic bitumen behavior depending on characteristics of different material phases. The definition and demarcation, respectively, of material phases is based on SARA fractions, and polarity considerations that support the assumption of asphaltene micelle structures within a contiguous matrix and the assumed interactions between them. A sufficient number of static creep tests on artificially composed bitumen samples with asphaltene contents from 0 to 30 wt% served both as identification as well as validation experiments for the developed micromechanical model. An excellent agreement between experimental results and model predictions indicates that the model is able to reproduce significant microstructural effects, such as interactions between asphaltenes, which strongly influence the bitumen behavior. This model is therefore expected to contribute to a better understanding of the influence of the bitumen microstructure on the macroscopic mechanical behavior and subsequently be able to describe the mechanical consequences of microstructural effects like aging. [ABSTRACT FROM AUTHOR]

Inhibition of the androgen receptor (AR) by second-generation anti-androgens is a standard treatment for metastatic castration resistant prostate cancer (mCRPC), but it inevitably leads to the development of resistance. Since the introduction of highly efficient AR signalling inhibitors, approximately 20% of mCRPC patients develop disease with AR independent resistance mechanisms. In this study, we generated two anti-androgen and castration resistant prostate cancer cell models that do not rely on AR activity for growth despite robust AR expression (AR indifferent). They are thus resistant against all modern AR signalling inhibitors. Both cell lines display cross-resistance against the chemotherapeutic drug docetaxel due to MCL1 upregulation but remain sensitive to the PARP inhibitor olaparib and the pan-BCL inhibitor obatoclax. RNA-seq analysis of the anti-androgen resistant cell lines identified hyper-activation of the E2F cell-cycle master regulator as driver of AR indifferent growth, which was caused by deregulation of cyclin D/E, E2F1, RB1, and increased Myc activity. Importantly, mCRPC tissue samples with low AR activity displayed the same alterations and increased E2F activity. In conclusion, we describe two cellular models that faithfully mimic the acquisition of a treatment induced AR independent phenotype that is cross-resistant against chemotherapy and driven by E2F hyper-activation. [ABSTRACT FROM AUTHOR]