Ultrafast photoinduced reflectivity transients in (Nd0.5Sr0.5)MnO3(Nd_{0.5}Sr_{0.5})MnO_3

The temperature dependence of ultrafast photoinduced reflectivity transients is reported in Nd$_{0.5}$Sr$_{0.5}$MnO$_{3}$ thin film. The photoinduced reflectivity shows a complex response with very different temperature dependences on different timescales. The response on the sub-ps timescale appears to be only weakly sensitive to the 270K-metal-insulator phase transition. Below $\sim 160$ K the sub-ps response displays a two component behavior indicating inhomogeneity of the film resulting from the substrate induced strain. On the other hand, the slower response on the 10-100 ps timescale is sensitive only to the metal-insulator phase transition and is in agreement with some previously published results. The difference in the temperature dependences of the responses on nanosecond and $\mu$s timescales indicates that thermal equilibrium between the different degrees of fredom is established relatively slowly - on a nanosecond timescale

Predicting Tumor Responses to Mitomycin C on the Basis of DT-Diaphorase Activity or Drug Metabolism by Tumor Homogenates: Implications for Enzyme-directed Bioreductive Drug Development

Mitomycin C (MMC) is a clinically used anticancer drug that is reduced to cytotoxic metabolites by cellular reductases via a process known as bioreductive drug activation. The identification of key enzymes responsible for drug activation has been investigated extensively with the ultimate aim of tailoring drug administration to patients whose tumors possess the biochemical machinery required for drug activation. In the case of MMC, considerable interest has been centered upon the enzyme DT-diaphorase (DTD) although conflicting reports of good and poor correlations between enzyme activity and response in vitro and in vivo have been published. The principle aim of this study was to provide a definitive answer to the question of whether tumor response to MMC could be predicted on the basis of DTD activity in a large panel of human tumor xenografts. DTD levels were measured in 45 human tumor xenografts that had been characterized previously in terms of their sensitivity to MMC in vitro and in vivo (the in vivo response profile to MMC was taken from work published previously). A poor correlation between DTD activity and antitumor activity in vitro as well as in vivo was obtained. This study also assessed the predictive value of an alternative approach based upon the ability of tumor homogenates to metabolize MMC. This approach is based on the premise that the overall rate of MMC metabolism may provide a better indicator of response than single enzyme measurements. MMC metabolism was evaluated in tumor homogenates (clarified by centrifugation at 1000 × g for 1 min) by measuring the disappearance of the parent compound by HPLC. In responsive [T/C 50%) tumors, the mean half life of MMC was 75 ± 48.3 and 280 ± 129.6 min, respectively. The difference between the two groups was statistically significant (P < 0.005). In conclusion, these results unequivocally demonstrate that response to MMC in vivo cannot be predicted on the basis of DTD activity. Measurement of MMC metabolism by tumor homogenates on the other hand may provide a better indicator of tumor response, and further studies are required to determine whether this approach has real clinical potential in terms of individualizing patient chemotherapy

CASSE - The ROSETTA Lander Comet Acoustic Surface Sounding Experiment - status of some aspects, the technical realisation and laboratory simulations

In 2003 the ROSETTA space mission to Comet 46P/Wirtanen will be launched by the European Space Agency (ESA). On board of the spacecraft there will be a Lander platform, which opens for the first time the possibility to carry out "in situ" measurements on a comet surface. The ROSETTA Lander experiment CASSE aims to investigate the outermost surface of the comet by means of transmitting, receiving and even passively monitoring acoustic waves in a frequency range from a few hundred to several kilohertz. In particular, by transmitting and recording compression and shear waves, the mechanical properties of the comentary surface will be investigated. To quarantee sufficient ground contact in any foreseeable surface topography, and in any composition of the material to be encountered, e.g. dust, sand, ice and mixtures of these materials, the acoustic transmitters (actuators), stacked piezoceramics, and triaxial commercial piezoelectric accelerometers as receivers, will be integrated in each of the three feet of the ROSETTA Lander. The Lander feet thus act as antennas for the transmitters and receivers. By switching different actuators and accelerometers, an analysis of the cometary surface material will become possible by direct foot to foot transmission of the acoustic signals. Further, an in-depth sounding will allow the detection of layered stuctures or embedded local inhomogeneities. The ground contact of the Lander will be strengthened by a harpoon providing a fixation force up to at least 5 N per foot. This paper describes the first design of the Lander feet incorporating piezoceramic composite stacks as sound transmiters and receivers, and the experiments to test their efficiency. In the first part of this paper, the results of acoustic wave propagation experiments in ice, sand and olivine dust, performed in the laboratory are reported. These experiments verify that a signal strength of at least 20 dB above noise can be expected for aacoustic wave propagation in cometary analogue materials. The second part of the paper deals with the outdoor experiments, performed with sensors integrated into the Lander feet prototypes and placed in a sand filled construction container. The experiments serve to estimate the minimal range of detectability of the sounding signals

Hypoxia-regulated glucose transporter Glut-1 may influence chemosensitivity to some alkylating agents: results of EORTC (First Translational Award) study of the relevance of tumour hypoxia to the outcome of chemotherapy in human tumour-derived xenografts.

Tumour hypoxia confers poor prognosis in a wide range of solid tumours, due to an increased malignancy, increased likelihood of metastasis and treatment resistance. Poorly oxygenated tumours are resistant to both radiation therapy and chemotherapy. However, although the link between radiation therapy and hypoxia is well established in a range of clinical studies, evidence of its influence on chemotherapy response is lacking. In this study, a panel of human tumour-derived xenografts that have been characterised previously for in vivo response to a large series of anti-cancer agents, and have been found to show chemosensitivities that correlate strongly with the parent tumour, were used to address this issue. Immunohistochemistry was carried out on formalin-fixed, paraffin-embedded sections of xenograft samples to detect expression of the intrinsic hypoxia marker Glut-1 and adducts of the bioreductive hypoxia marker pimonidazole. Glut-1 scores correlated significantly with T/C values for CCNU sensitivity (r = 0.439, P = 0.036, n = 23) and showed a borderline significant correlation with dacarbazine T/C (r = 0.405, P = 0.076, n = 20). However, there was no correlation between both Glut-1 and pimonidazole scores and T/C obtained for the bioreductive drug mitomycin C. The use of human tumour-derived xenografts offers a potentially useful way of using archival material to determine the influence of hypoxia and other tumour-microenvironmental factors on chemosensitivity without the direct use of human subjects