Combination cytotoxic effects of cis-diamminedichloroplatinum(II) and 5-fluorouracil with and without leucovorin against human non-small cell lung cancer cell lines

Both cisplatin (CDDP) and leucovorin (LV) have been shown to enhance cytotoxicity of 5-fluorouracil (FUra) against murine and human neoplasms by increasing intracellular reduced folate concentrations. We were interested in their use in a combination to inhibit non-small cell lung cancer (NSCLC) cell growth and therefore conducted an in vitro study to investigate the cytotoxic activities of combinations of CDDP plus FUra, with and without LV (20 microM), against seven NSCLC cell lines. A tetrazolium assay with application of the classical isobole method was used to test drug combinations. We found that LV enhanced FUra but not CDDP cytotoxicity and that the degree of enhancement was negatively correlated with the effect of FUra. There was an overall additive combination effect of CDDP plus FUra, although there may be synergy at higher effect levels. There was synergy to a combination of CDDP, FUra, and LV, presumably primarily related to the synergistic effects of adding LV to FUra. In summary, LV and CDDP enhanced FUra cytotoxicity in a complementary fashion and there was clear synergy of a combination of CDDP, FUra, and LV against a panel of NSCLC cell lines. Our in vitro results provide a rationale for controlled clinical studies of this three-drug regimen in patients with NSCLC.     

Role of conserved Asn-Tyr-Asp-Tyr sequence in bacterial copper/2,4, 5-trihydroxyphenylalanyl quinone-containing histamine oxidase

Copper amine oxidase contains a covalently bound quinonoid cofactor, 2,4,5-trihydroxyphenylalanyl quinone (TPQ), which is synthesized by post-translational modification of a specific tyrosyl residue occurring in the highly conserved sequence, Asn-Tyr-(Asp/Glu)-Tyr. To elucidate the role(s) of the conserved sequence in the biogenesis of TPQ, each of the corresponding residues at positions 401-404 in the recombinant histamine oxidase from Arthrobacter globiformis has been replaced with other amino acids by site-directed mutagenesis. When Asn-401 was changed to Asp or Gln, the rate of TPQ formation by copper-dependent self-processing was 10(3)- to 10(4)-fold slower than in the wild-type enzyme. When Tyr-402 was replaced by Phe, TPQ was not formed at all, showing that Tyr-402 is essential as the precursor to TPQ. In contrast, Asp-403 could be replaced by Glu without changes in the rate of TPQ formation, whereas its replacement by Asn led to a marked decrease. Furthermore, when Tyr-404 was changed to Phe, TPQ was formed swiftly on incubation with copper ions, but the TPQ enzyme exhibited very low activity with altered substrate specificity. These results collectively indicate that a very rigorous structural motif is required for efficient formation of TPQ and for the catalytic activity in the active site of copper amine oxidases.     

Reduction of loading effect by tungsten etchback in a magneticallyenhanced reactive ion etcher

The plug loading effect occurring during the etchback of tungsten was investigated in a magnetically enhanced reactive ion etcher using SF ₆/Ar mixtures. It was found that while the plug loading effect is independent of varying SF₆/Ar flow rate ratio and magnetic field intensity, it is reduced under the condition of high selectivity of tungsten relative to TiN which was achieved at high chamber pressure and low RF power. It is proposed that when TiN is used as a glue layer, the W etch rate enhancement in the plug is mainly controlled by a local loading effect. Under the optimized etchback conditions the plug loss was successfully controlled without the tungsten residue left on severe topology     

Arousal, numbing, and intrusion: symptom structure of PTSD following assault

OBJECTIVE: This study investigated hypotheses concerning the importance of symptoms of numbing in posttraumatic stress disorder (PTSD). METHODS: Symptoms of PTSD were assessed in 72 female rape victims and 86 female victims of nonsexual assault approximately 3 months after the crimes occurred. A principal-components factor analysis of subjects' symptoms was then undertaken. RESULTS: The analysis yielded three factors: arousal/avoidance, numbing, and intrusion. These were somewhat different from the symptom clusters in DSM-III-R, since effortful avoidance and numbing symptoms did not load on the same factor. Numbing symptoms appeared to be particularly important in identifying individuals with PTSD. CONCLUSIONS: The results imply that there are two patterns of posttrauma symptoms, one characterizing PTSD and the second characterizing a phobic reaction.     

Analysis of culture fluorescence by a fiber-optic sensor inNicotiana tabacum plant cell culture

The on-line sensing of viable cell weight in plant cell culture process is applied to analysis and control of process. The fiber-optic fluorescence sensor was constructed to measure the NADH-dependent fluorescence inNicotiana tabacum plant cell culture and the analysis of fluorescence signal was done to be correlated with the viable cell weight. The structured kinetic model for cell growth was proposed to estimate the theoretical viable cell weight. The dimensional analysis was proposed for the interpretation of fluorescence signal, in which the path length, the inner filter effect and the hydrodynamic conditions were considered as the key factors on fluorescence signal. The dimensional analysis and empirical correlation of fluorescence signal to viable cell weight was applied to the interpretation of the detected fluorescence signal during cultivation. The proposed interpretation of fluorescence signal using dimensional analysis was well correlated with the viable cell weight estimated by the structured kinetic model as well as by empirical correlation.     

Multiresolution segmentation of respiratory electromyographicsignals

Analysis of respiratory electromyographic (EMG) signals in the study of respiratory control requires the detection of burst activity from background (signal segmentation), and focuses upon the determination of onset and cessation points of the burst activity (boundary estimation). The authors describe a new automated multiresolution technique for signal segmentation and boundary estimation. During signal segmentation, a new transitional segment is defined which contains the boundary between background a burst activity. Boundary estimation is then performed within this transitional segment. Boundary candidates are selected and a probability is attributed to each candidate, using an artificial neural network. The final boundary for a given transitional segment is the boundary estimate with the maximum a posteriori probability. This new method has proved accurate when compared to boundaries chosen by two investigators     

Strength,toughness and R-curve behaviour of SiC whisker-reinforced composite Si3N4 with reference to monolithic Si3N4

The flexural strength and fracture toughness of 30 vol% SiC whisker-reinforced Si₃N₄ material were determined as a function of temperature from 25 to 1400°C in an air environment. It was found that both strength and toughness of the composite material were almost the same as those of the monolithic counterpart. The room-temperature strength was retained up to 1100°C; however, appreciable strength degradation started at 1200°C and reached a maximum at 1400°C due to stable crack growth. In contrast, the fracture toughness of the two materials was independent of temperature with an average value of 5.66 MPam^1/2. It was also observed that the composite material exhibited no rising R-curve behaviour at room temperature, as was the case for the monolithic material. These results indicate that SiC whisker addition to the Si₃N₄ matrix did not provide any favourable effects on strength, toughness and R-curve behaviour.     

Non-linear properties of polymer cellular materials with a negative Poisson's ratio

Negative Poisson's ratio polymeric cellular solids (re-entrant foams) were studied to ascertain the optimal processing procedures which give rise to the smallest value of Poisson's ratio. The non-linear stress-strain relationship was determined for both conventional and re-entrant foams; it depended upon the permanent volumetric compression achieved during the processing procedure. Poisson's ratio of re-entrant foam measured as a function of strain was found to have a relative minimum at small strains. The toughness of re-entrant foam increased with permanent volumetric compression, and hence with density.