Comparative Cytotoxicity of Artemisinin and Cisplatin and Their Interactions with Chlorogenic Acids in MCF7 Breast Cancer Cells

In parts of Africa and Asia, self‐medication with a hot water infusion of Artemisia annua (Artemisia tea) is a common practice for a number of ailments including malaria and cancer. In our earlier work, such an extract showed better potency than artemisinin alone against both chloroquine‐sensitive and ‐resistant parasites. In this study, in vitro tests of the infusion in MCF7 cells showed high IC₅₀ values (>200 μM ). The combination of artemisinin and 3‐caffeoylquinic acid (3CA), two major components in the extract, was strongly antagonistic and gave a near total loss of cytotoxicity for artemisinin. We observed that the interaction of 3CAs with another cytotoxic compound, cisplatin, showed potentiation of activity by 2.5‐fold. The chelation of cellular iron by 3CA is hypothesized as a possible explanation for the loss of artemisinin activity.     

Vitrinite reflectance geothermometry and apparent heating duration in the Cerro Prieto geothermal field

Vitrinite reflectance measured in immersion oil (R_o) on kerogen extracted from hydrothermally altered mudstones in borehole M-84 at the Cerro Prieto geothermal field exhibit an increase in mean reflectance ( ) from 0.12 per cent at 0.24 km depth to 4.1 per cent at 1.7 km depth. Downhole temperatures measured over this interval increase from about 60° to 340°C. These data plotted against temperature fall along an exponential curve with a coefficient of determination of about 0.8. Other boreholes sampled in the field show similar relationships. A regression curve calculated for temperature and in borehole M-105 correctly predicts temperatures in other boreholes within the central portion of the geothermal system. The correlation between the reflectance values and logged temperature, together with consistent temperature estimates from fluid inclusion and oxygen isotope geothermometry, indicates that changes in are an accurate and sensitive recorder of the maximum temperature attained. Therefore, vitrinite reflectance can be used in this geothermal system to predict the undisturbed temperature in a geothermal borehole during drilling before it regains thermal equilibrium. Although existing theoretical functions which relate to temperature and duration of heating are inaccurate, empirical temperature- curves are still useful for geothermometry.A comparison of temperature- regression curves derived from nine boreholes within the Cerro Prieto system suggests that heating across the central portion of the field occurred penecontemporaneously, but varies near margins. Boreholes M-93 and M-94 appear to have cooled from their maximum temperatures, whereas M-3 and Prian-1 have only recently been heated.Comparison of the temperature- data from the Salton Sea, California, geothermal system indicates that the duration of heating has been longer there than at the Cerro Prieto field.     

Linear modelling of multivariable systems with pseudo-random binary input signals

Properties and methods of generation of pseudo-random binary signals are discussed. A theory of linear modelling is developed for multivariable systems in which these signals form the inputs. Modelling with delay operators and exponential weighting function operators is considered. Experimental results are presented to illustrate the theory.     

A rule-based procedure for generating programmable logic controller code from graphical input in the form of ladder diagrams

This paper is concerned with a procedure for the automatic generation of code for programmable logic controllers. Input to the procedure is data from a graphical model of the discrete event dynamic system which is to be implemented. The model is constructed in the form of a ladder diagram at a graphics workstation. The data are held as Prolog tuples, and Prolog is used in the procedure to implement a rule base through which the data are mapped into the programmable logic controller code. Underlying the rule base are two methodologies. The first is a top-down decomposition of the ladder diagram to a level of three basic structures. The second is a bottom-up integration of code based on these structures into code for the whole system. An example is used throughout and the approach is shown to be effective.     

cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed

Brief elevation in postsynaptic calcium in hippocampal CA1 neurons leads to prolonged changes in synaptic strength. The calcium may enter the postsynaptic neuron via different routes, such as voltage-gated calcium channels or glutamate receptor channels of N-methyl-D-aspartate type, and/or be released from intracellular stores. The manner in which the synapse is altered, leading to the expression of an enhanced/depressed synaptic strength, is still unclear. The present study, performed using whole-cell recording from CA1 pyramidal cells of three- to five-week-old guinea-pigs, shows that postsynaptic depolarization alone, allowing for calcium influx through voltage-gated calcium channels, leads to a synaptic potentiation characterized by an altered time-course of the evoked excitatory synaptic response, an unaltered coefficient of variation of that response and a decreased paired-pulse facilitation likely related to a postsynaptic mechanism. These characteristics contrasted with those of long-term potentiation induced via activation of N-methyl-D-aspartate receptor channels, where the time-course was unaltered, the coefficient of variation was decreased and no change in paired-pulse facilitation was observed. Synapses can thus have mechanistically separate, but co-existent, potentiations of synaptic transmission initiated from separate sources for postsynaptic calcium.     

Structure of kaolinite flocs formed in an aqueous medium

The structure evolution of kaolinite flocs during their formation in aqueous medium was studied under a scanning electron microscope by hypercritical drying with liquid CO₂, as a function of Fe electrolyte content. Without any Fe electrolyte, a sediment with uniform porosity formed by accumulation of particles under gravity. Fresh Fe electrolytes made it possible to aggregate the kaolinite particles to flocs with an architecture consistent with diffusion limited aggregation (DLA). With 0.67 mM Fe, a single shrinking DLA flocs layer formed. With 3.33 mM Fe, extensive face to face aggregation of the clay particles occurred and a sediment with preferred horizontal orientation accumulated. With 0.17 mM Fe a shrinking DLA floc layer and a uniformly porous accumulated sediment formed concurrently, while with 1.67 mM Fe a shrinking DLA floes layer and an accumulated sediment with preferred orientation formed concurrently.     

Fetal growth and hyperinsulinaemia in adult life

To explore the relation between reduced fetal growth and impaired glucose tolerance in adult life, an oral glucose tolerance test (75 g glucose) was carried out on 218 men and women, now aged around 50 years, who had been measured in detail at birth. Measurements of plasma concentrations of glucose and insulin were made at 0, 30, and 120 min. Fasting plasma concentrations of proinsulin and 32-33 split proinsulin were also measured. People in the highest category of birthweight tended to have the lowest plasma concentrations of insulin as adults at both 0 and 120 min, though both these relations were weak. Plasma insulin concentrations in adult life were more strongly related to abdominal circumference at birth than to birthweight. After adjusting for sex and body mass index, mean insulin concentrations at 0 min fell from 50 pmol l-1 to 46 pmol l-1 (p = 0.04) and at 120 min from 235 pmol l-1 to 144 pmol l-1 (p = 0.003) between people whose abdominal circumference at birth had been less than 11.5 in and those who abdominal circumference had been greater than 13 in. Plasma glucose concentrations at 120 min also fell with increasing abdominal circumference at birth. Because abdominal circumference at birth is an indicator of the growth of the liver in fetal life, one interpretation of these findings is that the sensitivity of the liver to insulin is permanently reduced if the intrauterine development of this organ is impaired.     

Using leg muscles as shock absorbers: theoretical predictions and experimental results of drop landing performance

The use of muscles as power dissipators is investigated in this study, both from the modellistic and the experimental points of view. Theoretical predictions of the drop landing manoeuvre for a range of initial conditions have been obtained by accounting for the mechanical characteristics of knee extensor muscles, the limb geometry and assuming maximum neural activation. Resulting dynamics have been represented in the phase plane (vertical displacement versus speed) to better classify the damping performance. Predictions of safe landing in sedentary subjects were associated to dropping from a maximum (feet) height of 1.6-2.0 m (about 11 m on the moon). Athletes can extend up to 2.6-3.0 m, while for obese males (m = 100 kg, standard stature) the limit should reduce to 0.9-1.3 m. These results have been calculated by including in the model the estimated stiffness of the 'global elastic elements' acting below the squat position. Experimental landings from a height of 0.4, 0.7, 1.1 m (sedentary males (SM) and male (AM) and female (AF) athletes from the alpine ski national team) showed dynamics similar to the model predictions. While the peak power (for a drop height of about 0.7 m) was similar in SM and AF (AM shows a +40% increase, about 33 W/kg), AF stopped the downward movement after a time interval (0.219 +/- 0.030 s) from touch-down 20% significantly shorter than SM. Landing strategy and the effect of anatomical constraints are discussed in the paper.     

An investigation into the relationships between area social characteristics and road accident casualties

This paper reports on the analysis of a data base created by merging road casualty information and census data for the former Lothian region in Scotland. The data base was established by assigning resident postcodes to each casualty record and relating these postcodes to the census data for the relevant census output area. Initially, consideration was given to the relationship between casualty frequencies and the distance of the accidents from the zones of residence. As might be anticipated, the casualty frequencies were higher nearer to the zones of residence, possibly due to higher exposure. Subsequently, the relationships between casualty rates and social deprivation indicators for the casualties' zone of residence were investigated. In general it was found that the casualty rates amongst residents from areas classified as relatively deprived were significantly higher than those from relatively affluent areas.