Low dose X-ray speckle visibility spectroscopy reveals nanoscale dynamics in radiation sensitive ionic liquids

X-ray radiation damage provides a serious bottle neck for investigating {\mu}s to s dynamics on nanometer length scales employing X-ray photon correlation spectroscopy. This limitation hinders the investigation of real time dynamics in most soft matter and biological materials which can tolerate only X-ray doses of kGy and below. Here, we show that this bottleneck can be overcome by low dose X-ray speckle visibility spectroscopy. Employing X-ray doses of 22 kGy to 438 kGy and analyzing the sparse speckle pattern of count rates as low as 6.7x10-3 per pixel we follow the slow nanoscale dynamics of an ionic liquid (IL) at the glass transition. At the pre-peak of nanoscale order in the IL we observe complex dynamics upon approaching the glass transition temperature TG with a freezing in of the alpha relaxation and a multitude of milli-second local relaxations existing well below TG. We identify this fast relaxation as being responsible for the increasing development of nanoscale order observed in ILs at temperatures below TG.Comment: 7 pages, 5 figure

SCCharts: The Railway Project Report

SCCharts is a visual language proposed in 2012 for specifying safety-critical reactive systems. We present the results of the first medium sized SCCharts case-study. The case-study was conducted in the context of the railway project performed by students at the Kiel University in the summer term 2014. The railway project is a regularly occurring student training project that teaches principles of concurrent cyber-physical systems on a complex live model railway demonstrator. This report presents details of the first medium size SCCharts models created during the project. We explain what additional language extensions to SCCharts were necessary and how they were implemented. To handle performance issues that arose while developing the controller, compiler enhancements became necessary and are evaluated here. Furthermore, the participants completed a survey at the end of the project to confirm the goals that the SCCharts language and our SCCharts tool chain are suitable to build complex controllers. In the survey, the participants compared both, the SCCharts language and our SCCharts tools, with other modeling and classical programming languages and tools

Dubious effects of methadone as an "anticancer" drug on ovarian cancer cell-lines and patient-derived tumor-spheroids

Background. The opioid agonist D, L-methadone exerts analgesic effects via the mu opioid receptor, encoded by OPRM1 and therefore plays a role in chronic pain management. In preclinical tumor-models D,L-methadone shows apoptotic and chemo-sensitizing effects and was therefore hyped as an off-label "anticancer" drug without substantiation from clinical trials. Its effects in ovarian cancer (OC) are completely unexplored. Methods. We analyzed OPRM1-mRNA expression in six cisplatin-sensitive, two cisplatin-resistant OC cell-lines, 170 OC tissue samples and 12 non-neoplastic control tissues. Pro-angiogenetic, cytotoxic and apoptotic effects of D,L-methadone were evaluated in OC cell-lines and four patient-derived tumor-spheroid models. Results. OPRM1 was transcriptionally expressed in 69% of OC-tissues and in three of eight OC cell-lines. D, L-methadone exposure significantly reduced cell-viability in five OC cell-lines irrespective of OPRM1 expression. D, L-methadone, applied alone or combined with cisplatin, showed no significant effects on apoptosis or VEGF secretion in cell-lines. Notably, in two of the four sphero id models, treatment with D, L-methadone significantly enhanced cell growth (by up to 121%), especially after long-term exposure. This is consistent with the observed attenuation of the inhibitory effects of cisplatin in three spheroid models when adding D, L-methadone. The effect of methadone treatment on VEGF secretion in tumor-spheroids was inconclusive. Conclusions. Our study demonstrates that certain OC samples express OPRM1, which, however, is not a prerequisite for D, L-methadone function. As such, D,L-methadone may exert also detrimental effects by stimulating the growth of certain OC-cells and abrogating cisplatin's therapeutic effect. (C) 2022 The Authors. Published by Elsevier Inc.Peer reviewe

Coherent X-ray Scattering Reveals Nanoscale Fluctuations in Hydrated Proteins

Hydrated proteins undergo a transition in the deeply supercooled regime, which is attributed to rapid changes in hydration water and protein structural dynamics. Here, we investigate the nanoscale stress relaxation in hydrated lysozyme proteins stimulated and probed by X-ray Photon Correlation Spectroscopy (XPCS). This approach allows us to access the nanoscale dynamic response in the deeply supercooled regime (T = 180 K) which is typically not accessible through equilibrium methods. The relaxation time constants exhibit Arrhenius temperature dependence upon cooling with a minimum in the Kohlrausch-Williams-Watts exponent at T = 227 K. The observed minimum is attributed to an increase in dynamical heterogeneity, which coincides with enhanced fluctuations observed in the two-time correlation functions and a maximum in the dynamic susceptibility quantified by the normalised variance $\chi_T$. Our study provides new insights into X-ray stimulated stress relaxation and the underlying mechanisms behind spatio-temporal fluctuations in biological granular materials