3D Micro-PIXE at atmospheric pressure: A new tool for the investigation of art and archaeological objects

The paper describes a novel experiment characterized by the development of a confocal geometry in an external Micro-PIXE set-up. The position of X-ray optics in front of the X-ray detector and its proper alignment with respect to the proton micro-beam focus provided the possibility of carrying out 3D Micro-PIXE analysis. As a first application, depth intensity profiles of the major elements that compose the patina layer of a quaternary bronze alloy were measured. A simulation approach of the 3D Micro-PIXE data deduced elemental concentration profiles in rather good agreement with corresponding results obtained by electron probe micro-analysis from a cross-sectioned patina sample. With its non-destructive and depth-resolving properties, as well as its feasibility in atmospheric pressure, 3D Micro-PIXE seems especially suited for investigations in the field of cultural heritage.     

Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

In search of trustworthy information: a qualitative study of the search behavior of people with dyslexia in Norway

Universal Access in the Information Society - Access to trustworthy information is a premise for participation in a democratic society. However, locating useful and valid information may not be a...     

Autonomic information flow improves prognostic impact of task force HRV monitoring

Heart rate variability (HRV) represents the cardiovascular control mediated by the autonomic nervous system and other mechanisms. In the established task force HRV monitoring different cardiovascular control mechanisms can approximately be identified at typical frequencies of heart rate oscillations by power spectral analysis. HRV measures assessing complex and fractal behavior partly improved clinical risk stratification. However, their relationship to (patho-)physiology is not sufficiently explored. Objective of the present work is the introduction of complexity measures of different physiologically relevant time scales. This is achieved by a new concept of the autonomic information flow (AIF) analysis which was designed according to task force HRV. First applications show that different time scales of AIF improve the risk stratification of patients with multiple organ dysfunction syndrome and cardiac arrest patients in comparison to standard HRV. Each group's significant time scales correspond to their respective pathomechanisms.     

SK119, a Novel Shikonin Derivative,Leads to Apoptosis in Melanoma Cell Lines and Exhibits Synergistic Effects with Vemurafenib and Cobimetinib

Melanoma is a complex and heterogenous disease, displays the deadliest form of skin cancer, and accounts for approx. 80% of all skin cancer deaths. In this study, we reported on the synthesis and pharmacological effects of a novel shikonin derivative (SK119), which is active in a nano-molar range and exhibits several promising in vitro effects in different human melanoma cells. SK119 was synthesized from shikonin as part of our search for novel, promising shikonin derivatives. It was screened against a panel of melanoma and non-tumorigenic cell lines using XTT viability assays. Moreover, we studied its pharmacological effects using apoptosis and Western blot experiments. Finally, it was combined with current clinically used melanoma therapeutics. SK119 exhibited IC₅₀ values in a nano-molar range, induced apoptosis and led to a dose-dependent increase in the expression and protein phosphorylation of HSP27 and HSP90 in WM9 and MUG-Mel 2 cells. Combinatorial treatment, which is highly recommended in melanoma, revealed the synergistic effects of SK119 with vemurafenib and cobimetinib. SK119 treatment changed the expression levels of apoptosis genes and death receptor expression and exhibited synergistic effects with vemurafenib and cobimetinib in human melanoma cells. Further research indicates a promising potential in melanoma therapy.     

Beyond the fascination of online-games: Probing addictive behavior and depression in the world of online-gaming

This study examined problematic gaming behavior and depressive tendencies among people who play different types of online-games. Other game-related variables were investigated to determine if other differences between three game types could be established. Participants in the current research (n = 468) can be classified into three independent groups. Subjected users either solely played massive multiplayer online role-playing games (MMORPGs) or they preferred online-ego-shooters (OES) or real-time-strategy games (RTS). Results indicate that MMORPG users show more often problematic gaming behavior, depressive tendencies and lower self-esteem compared to users playing other online-games. MMORPG users reported to playing significantly more often in order to escape from real-life problems, which might be a valuable coping strategy but might also lead to problematic gaming behavior.     

Unraveling Membrane Perturbations Caused by the Bacterial Riboregulator Hfq

Hfq is a pleiotropic regulator that mediates several aspects of bacterial RNA metabolism. The protein notably regulates translation efficiency and RNA decay in Gram-negative bacteria, usually via its interaction with small regulatory RNAs. Previously, we showed that the Hfq C-terminal region forms an amyloid-like structure and that these fibrils interact with membranes. The immediate consequence of this interaction is a disruption of the membrane, but the effect on Hfq structure was unknown. To investigate details of the mechanism of interaction, the present work uses different in vitro biophysical approaches. We show that the Hfq C-terminal region influences membrane integrity and, conversely, that the membrane specifically affects the amyloid assembly. The reported effect of this bacterial master regulator on membrane integrity is discussed in light of the possible consequence on small regulatory RNA-based regulation.