Why Solidification? Why Phase-Field?

“Solidification” is a branch of pattern formation in theoretical physics. “Phase-field” is an applied tool in engineering. This strange combination of basic and applied research is reviewed against its historical background: a story of failure and success. The main achievements in both fields are highlighted, and future perspectives are briefly discussed.     

Impact of copper on the induction and repair of oxidative DNA damage, poly(ADP-ribosyl)ation and PARP-1 activity

Copper is an essential trace element involved, among other functions, in enzymatic antioxidative defense systems. However, nonprotein bound copper ions have been shown to generate reactive oxygen species. To gain insight into the discrepancy between the protective properties of copper on the one hand and its toxicity on the other hand, we examined the genotoxic effects of CuSO(4) in cultured human cells. Here we report that copper, at cytotoxic concentrations, induces oxidative DNA base modifications and DNA strand breaks. However, at lower noncytotoxic concentrations, copper inhibits the repair of oxidative DNA damage induced by visible light. As a first mechanistic hint, inhibition of H(2)O(2)-induced poly(ADP-ribosyl)ation was identified in cultured cells and further experiments demonstrated a strong inhibition of the activity of isolated poly(ADP-ribose)polymerase-1 (PARP-1) by copper. Bioavailability studies of copper showed a dose-dependent uptake in cells and pointed out the relevance of the applied concentrations. Taken together, the results indicate that copper, under conditions of either disturbed homeostasis or overload due to high exposure, exerts defined genotoxic effects. Hence, a balance needs to be maintained to ensure sufficient uptake and to prevent overload.     

Cross sections for neutron-induced reactions up to 1.6 GeV for target elements relevant for cosmochemical, geochemical, and technological applications

We determined neutron excitation functions from the respective reaction thresholds up to 1.6 GeV for almost 100 target-product combinations relevant for cosmochemical, geochemical, and technological applications. We started with thick target production rates that have been obtained by irradiating iron and stone spheres with protons having energies between 600 MeV and 1.6 GeV. From the particle spectra of primary protons, secondary protons, and secondary neutrons, and the usually well known cross sections for the proton-induced reactions we calculated the production rates only due to protons. By subtracting these data from the measured total production rates we obtained production rates only due to secondary neutrons. With the modelled neutron spectra, guess functions calculated using nuclear model codes, and sophisticated energy-dependent deconvolution procedures we were able to determine almost 100 neutron excitation functions with their uncertainties. With the thus obtained neutron cross sections we are able to describe the experimental production rates in the thick target experiments, meteorites, the lunar surface, and terrestrial surface samples usually within the uncertainties, i.e., to within 10-15%. The adjusted neutron cross sections (a posteriori) are compared to results from the theoretical nuclear model codes INCL4.5/ABLA07 and TALYS. The TALYS code usually describes the a posteriori data reasonably well, i.e., mostly within a factor of a few. The quality of the INCL4.5 + ABLA07 predictions depends on the reaction type and increases with increasing number of ejectiles, i.e., increasing target-product mass difference. The neutron cross section database, though successful in quantifying production rates in terrestrial and extraterrestrial matter, presents by no means a final step and experiments with quasi-monoenergetic neutrons are needed.     

Dark roast coffee is more effective than light roast coffee in reducing body weight, and in restoring red blood cell vitamin E and glutathione concentrations in healthy volunteers

Recent results from prospective cohort studies have shown that moderate coffee consumption is associated with a reduced risk for diabetes mellitus type II or Alzheimer's disease. Since reactive oxygen species (ROS) are believed to be involved in the pathogenesis of these diseases, antioxidants in coffee might contribute to this risk reduction. We aimed at elucidating whether a dark roast coffee beverage (CB) rich in N‐methylpyridinium ions (NMP: 785 μmol/L) and low in chlorogenic acids (CGA: 523 μmol/L) has stronger antioxidant effects on human erythrocytes than a CB prepared from a light roast with opposite proportions (CGA: 4538 μmol/L; NMP: 56 μmol/L). Following a 2‐wk wash out period, 500 mL of the respective CB was administered to 30 subjects daily for 4‐wk. Blood and spot urine samples were collected at the beginning and at the end of each intervention. Intake of the dark roast CB most effectively improved the antioxidant status of erythrocytes: superoxide dismutase and glutathione peroxidase activity decreased by 5.8 and 15%, respectively, whereas tocopherol and total glutathione concentrations increased by 41 and 14%, respectively. Furthermore, administration of the NMP‐rich CB led to a significant body weight reduction in pre‐obese subjects, whereas the CGA‐rich CB did not.     

Polyethylene and cobalt–chromium molybdenium particles elicit a different immune response in vitro

Periprosthetic osteolysis is a major clinical problem that limits the long-term survival of total joint arthroplasties. Particles of prosthetic material stimulate immune competent cells to release cytokines, which may cause bone loss and loosening of the prosthesis. This study examined the following hypothesis. Polyethylene and titanium particles elicit a different immune response in vitro. To test these hypotheses, we used the human bone marrow cell culture model that we have established and previously used to examine particle associated cytokine release. Ultra high molecular weight polyethylene (UHMW-PE) induced a proliferation of CD14 positive cells (monocytes/macrophages) whereas cobalt chromium molybdenium (CoCrMb) particles demonstrated an increased proliferation of CD66b positive cells (granulocytes). Light and scanning microscopic evaluation revealed that the UHMW-PE particles, which have built large clusters of particles (Ø7, 5 μm), were mainly surrounded by the cells and less phagocytosed. On the other hand the smaller particles from CoCrMb have been phagocytosed by the cells. These results provide strong support for our hypothesis: that wear particles derived from prosthetic materials of different material can elicit significantly different biologic responses. In summary the results suggest that the “in vitro” response to wear particles of different biomaterials should be investigated by culture systems of various lineages of cells.     

A comparison of different nanostructured biomaterials in subcutaneous tissue

The nanostructured surface of a material can improve its interaction with cells and its acceptance as an implant. We compared two novel biomaterials with different nanostructures: Bioverit((R)) II with a coating of nanoporous silica and chitosan-hydroxyapatite composite materials. Pure Bioverit((R)) II served as a control. Platelets of these materials were implanted for 28, 85 and 300 days in the subcutaneous tissue in the neck of 38 rabbits. After excising the specimens they were fixed, embedded in epoxy resin and analyzed histologically. All coated Bioverit((R)) II implants showed a thin capsule of connective tissue. After 300 days, these capsules tended to be thicker than in pure Bioverit((R)) II. No signs of inflammation were observed and the materials appeared unaltered by visual inspection. In case of chitosan-hydroxyapatite composites, massive capsules consisting of dense connective tissue were found, and the material showed signs of biodegradation in form of fissures and cavities. In conclusion, the nanoporous coating showed no obvious positive effect with regard to capsule formation; the chitosan-hydroxyapatite implants provoked a stronger interaction between cells and material. However, most Bioverit((R)) II implants showed no alterations optically, whereas chitosan-hydroxyapatite was partly degraded in all cases.     

Towards an integrated description of hydrogen bonding and dehydration: decreasing false positives in virtual screening with the HYDE scoring function

We developed a new empirical scoring function, HYDE, for the evaluation of protein-ligand complexes. HYDE estimates binding free energy based on two terms for dehydration and hydrogen bonding only. The essential feature of this scoring function is the integrated use of log P-derived atomic increments for the prediction of free dehydration energy and hydrogen bonding energy. Taking the dehydration of atoms within the interface into account shows that some atoms contribute favorably to the overall score, while others contribute unfavorably. For instance, hydrogen bond functions are penalized if they are dehydrated unless they can overcompensate this loss by forming a hydrogen bond with excellent geometry. The main stabilizing contribution represents the removal of apolar groups from the water: the hydrophobic effect. Initial studies using the DUD dataset show that with HYDE, there is a significant decrease in false positives, a reasonable categorization of compounds as either non-binders, weak, medium or strong binders, and in particular, there is a generally applicable and thermodynamically sensible cutoff score below which there is a high likelihood that the compound is indeed a binder.