Partial Reduction in BRCA1 Gene Dose Modulates DNA Replication Stress Level and Thereby Contributes to Sensitivity or Resistance

BRCA1 is a well-known breast cancer risk gene, involved in DNA damage repair via homologous recombination (HR) and replication fork protection. Therapy resistance was linked to loss and amplification of the BRCA1 gene causing inferior survival of breast cancer patients. Most studies have focused on the analysis of complete loss or mutations in functional domains of BRCA1. How mutations in non-functional domains contribute to resistance mechanisms remains elusive and was the focus of this study. Therefore, clones of the breast cancer cell line MCF7 with indels in BRCA1 exon 9 and 14 were generated using CRISPR/Cas9. Clones with successful introduced BRCA1 mutations were evaluated regarding their capacity to perform HR, how they handle DNA replication stress (RS), and the consequences on the sensitivity to MMC, PARP1 inhibition, and ionizing radiation. Unexpectedly, BRCA1 mutations resulted in both increased sensitivity and resistance to exogenous DNA damage, despite a reduction of HR capacity in all clones. Resistance was associated with improved DNA double-strand break repair and reduction in replication stress (RS). Lower RS was accompanied by increased activation and interaction of proteins essential for the S phase-specific DNA damage response consisting of HR proteins, FANCD2, and CHK1.     

Contact and thermal analysis of an alumina—steel dry sliding friction pair considering the surface roughness

In the present study, finite element transient contact and thermal sliding simulation and temperature measurement of dry sliding friction were performed in order to analyse the real contact area and temperature developed in the contact region. Real 3D surface worn topographies were taken into consideration, at macro and intermediate stages. The calculated real contact area has been changing in time and space in the course of sliding. The sliding components were high purity alumina ceramic palettes and 100Cr6 steel with constant accelerated motion. The calculated temperature results are in good agreement with the temperature data measured. Heat partition was changing in time during sliding. The developed algorithm based on incremental FE technique can characterize real processes.     

Species differences in the physical and transport properties of airway secretions

Four cases of severe Lepiota poisoning, including three which developed toxic fulminant hepatitis treated by orthotopic hepatic transplantation, are reported here. The toxicity of the Lepiota is discussed as well as the indications for hepatic transplantation in poisonings due to amatoxin-containing mushrooms.     

Shape optimization of structural parts in dynamic mechanical systems based on fatigue calculations

In this paper a new method for an automated shape optimization of dynamically loaded components in mechanical systems is presented. The optimization is carried out by means of the results of a durability analysis based on finite elements. Load time histories, which are necessary for durability analyses, are derived from a multibody simulation. The whole optimization loop, which is an iterative procedure, incorporates all these gradual analysis steps and is implemented by the authors in a straightforward, batch-oriented manner using well-known standard software. Since the whole process involves several different analysis types, such as multibody system simulation and durability analysis, the resulting setup is rather complex. Furthermore, the reader may not be familiar with all the terms arising within the context of every single analysis domain. Therefore, some essential aspects of each of the stages involved in the process are explained to provide the reader with the necessary background. In the following, the required software setup as well as the implementation are described. Finally, an academic example is discussed to illustrate and clearly outline the potential of this method.     

Retinoic acid receptor gamma1 expression determines retinoid sensitivity in pancreatic carcinoma cells

A highly enriched spindle pole preparation was prepared from budding yeast and fractionated by SDS gel electrophoresis. Forty-five of the gel bands that appeared enriched in this fraction were analyzed by high-mass accuracy matrix-assisted laser desorption/ ionization (MALDI) peptide mass mapping combined with sequence database searching. This identified twelve of the known spindle pole components and an additional eleven gene products that had not previously been localized to the spindle pole. Immunoelectron microscopy localized eight of these components to different parts of the spindle. One of the gene products, Ndc80p, shows homology to human HEC protein (Chen, Y., D.J. Riley, P-L. Chen, and W-H. Lee. 1997. Mol. Cell Biol. 17:6049-6056) and temperature-sensitive mutants show defects in chromosome segregation. This is the first report of the identification of the components of a large cellular organelle by MALDI peptide mapping alone.     

Thermodynamic activities and phase boundaries for the alloys of the solid solution of Co in Ni3Al

The vaporization of the alloy samples of the compositions (Ni₃Al)_1-x Co _x (x = 0, 0.03, 0.06, 0.09, 0.12, or 0.15) was investigated at temperatures between 1326 to 1581 K by the use of Knudsen effusion mass spectrometry in order to obtain thermodynamic data for the solid solution γ′ phase of the type Ni₃Al. The partial pressures of Al, Co, and Ni were determined over the samples investigated. Excess chemical potentials at a temperature of 1473 K resulted for the components in the γ′ solubility range. New results on the phase boundaries of the γ′ solubility lobe were obtained by the analysis of quenched alloy samples and from the mass spectrometric studies. The results obtained are discussed with respect to the solubility behavior of Co in the γ′ phase.     

Production and characterization of ITO-Pt semiconductor powder containing nanoscale noble metal particles catalytically active in dye-sensitized solar cells

Doped indium tin oxide (ITO) samples of a surface area around 60 m²/g have been synthesized. As doping component platinum and gold atoms were utilized, respectively. The powders were produced by pyrolyzing mixed metal oxide precursors in a first zone in a flame consisting of hydrogen and air, metering a noble metal compound and reducing gas into a second zone of the flame and separating off the solid obtained in a third zone. Well-defined solid phases In₂Pt and In₂Au in ITO were obtained, respectively. The production of a mixture with discrete SnO₂ entities could be avoided. The mixed oxide powder doped with platinum can be used as a catalyst. The structure and composition of materials obtained at different levels of platinum dosing into a flame reactor has been determined. The size of the noble metal-containing entities ranged at about 3.5–5.5 nm. The catalytic properties of these oxides containing noble metal have been utilized in the fabrication of dye-sensitized solar cells (DSCs). Long term stability of DSCs containing liquid electrolytes requires a glass sealing of the two electrodes at a temperature of over 600 °C. Such high temperatures are detrimental to the catalytic activity of the conventional platinum layers in the counter electrode. Improved catalytic activity could be achieved by platinum entities bound to indium tin oxide. This catalytic material can effectively be used in the DSCs with glass sealing, the sealing temperature being over 600 °C. Spray pyrolysis in a flame reactor is highly suitable to produce noble metal-containing oxides in one single production step. Platinum-containing ITO particles from flame pyrolysis production exhibit superior catalytic activity in dye-sensitized solar cells compared to material from conventional thermal decomposition.     

On the simulation of molded micro components and systems

Regarding micro components and systems, experimental work for characterizing materials’ properties as well as components’ and systems’ behaviors have to be supplemented by numerical analyses. These analyses should cover component and system issues. On a component level, macroscopic approaches are extended by methods allowing consideration of the influence of components’ grain structures including possible defects. On a system level, the high tolerances accepted for the individual components due to production inaccuracy and their effects on the expected load distribution capability of the system are taken into account. This paper presents approaches for simulation of micro components and systems using the finite element method and multi body simulation. Methods to overcome the abovementioned issues will be shown, as well as the effects of grain structure on the stress distribution in the individual components.     

Spectroscopic studies on chemically reacted (oxidized) coals

Solid material is often the main product of chemically reacted coal. In this study, elemental analysis and infrared molecular spectroscopy were therefore used for characterizing the structural changes during reaction. Three seam coals were oxidized in a controlled gas-solid reaction at different temperatures. A group analysis provided detailed quantitative figures on composition versus time of reaction. Assuming first-order reaction, values for rate constants, apparent energies of activation and frequency factors were calculated, and mechanisms of reaction have been proposed for different oxidation steps.