Prolonged tamoxifen exposure selects a breast cancer cell clone that is stable in vitro and in vivo

The effects of long-term tamoxifen exposure on cell growth and cell cycle kinetics were compared between oestrogen receptor (ER)-positive (MCF-7) and ER-negative (MDA-MB-231) cell lines. In the MCF-7 cell line, prolonged tamoxifen exposure (0.5 mumol/l for > 100 days) blocked cells in G0-G1 of the cell cycle, and slowed the doubling time of cells from 30 to 59 h. These effects corresponded to an increase in the cellular accumulation of tamoxifen over time [mean area under concentration curve (AUC) = 77.92 mumoles/10(6)/cells/day]. In contrast, in the MDA-MB-231 cell line, long-term tamoxifen exposure had no obvious effect on the doubling time, and reduced cellular tamoxifen accumulation (mean AUC = 50.50 mumoles/10(6)/cells/day) compared to the MCF-7 cells. Flow cytometric analysis of MDA-MB-231 cells demonstrated that a new tetraploid clone emerged following 56 days of tamoxifen exposure. Inoculation of the MDA-MB-231 tetraploid clone and MDA-MB-231 wildtype cells into the opposite flanks of athymic nude mice resulted in the rapid growth of tetraploid tumours. The tetraploid tumours maintained their ploidy following tamoxifen treatment for nine consecutive serial transplantations. Histological examination of the fifth transplant generation xenografts revealed that the tetraploid tumour had a 25-30 times greater mass, area of haemorrhage and necrosis, a slightly higher mitotic index and was more anaplastic than the control neoplasm. The control wildtype MDA-MB-231 tumours maintained a stable ploidy following tamoxifen treatment until the eighth and ninth transplantation, when a tetraploid population appeared, suggesting that tamoxifen treatment may select for this clone in vivo. These studies suggest that prolonged tamoxifen exposure may select for new, stable, fast growing cell clones in vitro as well as in vivo.     

The measurement of fatty solids by differential scanning calorimetry

A method has been developed for the measurement of the solids content of vegetable and animal fats by differential scanning calorimetry. Although precision is about half that of existing dilatometric methods, this is a rapid procedure, designed for hydrogenation control. Elapsed analysis time for the determination of solids at two temperatures is about 40 min, compared with 3 to 4 hr by dilatometry. Procedures are outlined employing either of two commercially available instruments.     

Switching field distribution and A.C. bias recording parameters

A set of tapes has been prepared for audio recording measurements by mixing cobalt modified iron oxides for equal coercivity and remanence but varying switching field distribution (SFD). At low level recording the optimum high frequency bias current but not the maximum signal level was found to decrease with increasing SFD. The long wavelength output at 5% third harmonic distortion remains unchanged. The decrease of short wavelength saturated signal with increasing SFD was separated into demagnetization and bias current losses.     

Carbamazepine/betaCD/HPMC solid dispersions. I. Influence of the spray-drying process and betaCD/HPMC on the drug dissolution profile

The aim of this study was to compare carbamazepine (CBZ) solid dispersions prepared by spray-drying of aqueous dispersions with the corresponding physical mixtures. The influence of the association of β-cyclodextrin (βCD) and hydroxypropyl methylcellulose (HPMC) on the CBZ dissolution profile of the preparations was investigated. Results demonstrated that CBZ release from solid dispersions is dependent on the ratio of βCD and HPMC. The spray-drying process confers better homogeneity to CBZ polymeric dispersions than the physical mixture process. In summary, we demonstrated the feasibility of obtaining a homogeneous polymeric solid dispersion of CBZ from an aqueous media by spray-drying and a clear influence of the βCD:HPMC ratio on the release profile of CBZ.     

Atomistically informed crystal plasticity model for body-centered cubic iron

The glide of screw dislocations with non-planar dislocation cores dominates the plastic deformation behavior in body-centered cubic iron. This yields a strong strain rate and temperature dependence of the flow stress, the breakdown of Schmid’s law and a dependence of dislocation mobility on stress components that do not contribute to the mechanical driving force of dislocation glide. We developed a constitutive plasticity model that takes all these effects into account. The model is based on the crystal plasticity approach and parameterized by performing molecular statics calculations using a semi-empirical potential. The atomistic studies yield quantitative relations between local stress tensor components and the mobility of dislocations. Together with experimental stress–strain curves obtained for two different orientations of iron single crystals taken from the literature, the constitutive law is completely parameterized. The model is validated by comparing numerical single crystal tension tests for a third orientation to the equivalent experimental data from the literature. We also provide results for the temperature and strain rate dependence of the new atomistically informed constitutive model.     

Electron and hole mobility enhancement in strained SOI by waferbonding

N- and p-MOSFETs have been fabricated in strained Si-on-SiGe-on-insulator (SSOI) with high (15-25%) Ge content. Wafer bonding and H-induced layer transfer techniques enabled the fabrication of the high Ge content SiGe-on-insulator (SGOI) substrates. Mobility enhancement of 50% for electrons (with 15% Ge) and 15-20% for holes (with 20-25% Ge) has been demonstrated in SSOI MOSFETs. These mobility enhancements are commensurate with those reported for FETs fabricated on strained silicon on bulk SiGe substrates     

Atmospheric Effects on Compressive Creep of SiC-Whisker-Reinforced Alumina

A SiC-whisker-reinforced alumina composite was crept in compression at 1200° to 1400°C in an air ambient and in nitrogen. The data were described by a power-law-type constitutive relation. The measured value of the stress exponent was n = 1 at 1200°C and n = 3 at 1300° and 1400°C in both ambients. TEM observations were correlated with the measured creep response to determine active deformation mechanisms. Values of n = 1 were associated with diffusional creep and unaccommodated grain-boundary sliding, while values of n = 3 were associated with increased microstructural damage in the form of cavities. Experiments conducted in circulated air resulted in higher creep rates than comparable experiments in nitrogen. The accelerated creep rates were caused by the thermal oxidation of SiC and the resultant formation of a vitreous phase along composite interfaces. The glassy phase facilitated cavitation, weakened interfaces, and enhanced boundary diffusion.     

Psychophysiological characteristics and school performance of children in open and traditional classrooms.

98 children in 3 open and 3 traditional 1st-grade classrooms were observed and tested on physiological and performance measures (e.g., Star and Pyramid Mazes) at the beginning and end of their 1st yr of school. Skin conductance level and mean pulse rate were used to categorize subgroups as either high or low in physiological arousal level. It was predicted that the greater amount of external stimulation in an open classroom would provide a more suitable learning environment for low-arousal Ss in that their needs for stimulation would be satisfied and their behavioral manifestations of an arousal deficit would be reduced; the opposite was expected for high-arousal Ss. ANOVAs revealed that performance (e.g., visual discrimination scores) of high-arousal Ss in open classrooms decreased over time in contrast to all other S subgroups. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)