Interventional Treatment Strategies in Intrahepatic Cholangiocarcinoma and Perspectives for Combined Hepatocellular-Cholangiocarcinoma

cHCC-CCA is an uncommon type of liver cancer that exhibits clinical and pathological characteristics of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), which are the two main forms of primary liver cancer. The similarity to HCC and CCA makes therapeutical strategies challenging. The poor prognosis of CCA in general, as well as for cHCC-CCA, is mainly attributable to the fact that diagnosis is often at an advanced stage of disease. During the last decade, locoregional therapies usually performed by interventional radiologists and its established role in HCC treatment have gained an increasing role in CCA treatment as well. These comprise a wide range of options from tumor ablation procedures such as radiofrequency ablation (RFA), microwave ablation (MWA), computed tomography high-dose rate brachytherapy (CT-HDRBT), and cryoablation to transarterial chemoembolization (TACE), including the option of intra-arterial administration of radioactive spheres (transarterial radioembolization-TARE), and much attention has focused on the potential of individual concepts in recent years. The purpose of this review is to provide an overview of current radiologic interventions for CCA (excluding options for eCCA), to review and appraise the existing literature on the topic, and to provide an outlook on whether such interventions may have a role as treatment for cHCC-CCA in the future

Details Matter in Structure-based Drug Design

Successful structure-based drug design (SBDD) requires the optimization of interactions with the target protein and the minimization of ligand strain. Both factors are often modulated by small changes in the chemical structure which can lead to profound changes in the preferred conformation and interaction preferences of the ligand. We draw from examples of a Roche project targeting phosphodiesterase 10 to highlight that details matter in SBDD. Data mining in crystal structure databases can help to identify these sometimes subtle effects, but it is also a great resource to learn about molecular recognition in general and can be used as part of molecular design tools. We illustrate the use of the Cambridge Structural Database for identifying preferred structural motifs for intramolecular hydrogen bonding and of the Protein Data Bank for deriving propensities for protein-ligand interactions

"Zyflex": next generation plasma chamber for complex plasma research in space

Complex plasmas consist of highly charged micrometer-sized grains injected into a low temperature noble gas discharge. Since gravity has a strong influence on the particle system, experiments under microgravity conditions are essential. A novel plasma chamber (the "Zyflex" chamber) has been designed for complex plasma research in a future facility on the International Space Station (ISS). The cylindrical, radiofrequency driven discharge device includes a variety of innovations that for example allow to flexibly adjust plasma parameters and its volume. Compared to former chambers used in space based complex plasma facilities, it also supports much larger particle systems and can be operated at much lower gas pressures, thus reducing the damping of particle motion considerably. Beyond the technical description and particle-incell (PIC) simulation based characterization of the plasma vessel, we show sample results from experiments performed with this device in the lab as well as during parabolic flights. Further, an outlook on the future ISS facility COMPACT with the Zyflex chamber at its core is given. This work is funded by DLR/BMWi (FKZ 50WM1441)

Association between Fatty Acid Composition in Hair and Energy Availability during Early Lactation in Simmental and German Holstein Cows

This study examined (1) if fatty acids in bovine hair are influenced by dietary energy levels and (2) if the relationship between energy availability and fatty acids in hair persists across breeds and farms. Sixty-two and 59 Fleckvieh (Simmental), and 55 German Holstein cows from three farms, respectively, were fed two levels of energy concentration of roughage (6.1 and 6.5 MJ net energy for lactation/kg dry matter) and two levels of concentrate supply (150 and 250 g/kg energy-corrected milk). The average body weight was 727 kg (Simmental) and 668 kg (Holstein). The average lactation number was 3.1. Hair samples were taken in lactation weeks 4 and 8. In Simmental cows, a lower energy deficit due to a relatively higher energy intake from high energy concentration of the roughage was associated with higher C18:2n-6 and C18:3n-3 contents in hair at week 8. In cows from all three farms, higher energy intake between lactation weeks 2 and 6 correlated with higher content of C18:2n-6 in hair samples taken in lactation weeks 4 and 8. No correlation was found for C12:0. These results provide the first evidence that increased energy intake increases the contents of C18:2n-6 in hair