Oxidizing species in the mechanism of cytochrome P450

This review discusses the mechanisms of oxygen activation by cytochrome P450 enzymes, the possible catalytic roles of the various iron-oxygen species formed in the catalytic cycle, and progress in understanding the mechanisms of hydrocarbon hydroxylation, heteroatom oxidation, and olefin epoxidation. The focus of the review is on recent results, but earlier work is discussed as appropriate. The literature through to February 2002 is surveyed, and 175 referenced are cited.

Doubling daily inhaled corticosteroid dose is ineffective in mild to moderately severe attacks of asthma in adults

Background: Asthma guidelines recommend increasing or doubling inhaled corticosteroid (ICS) dose to treat mild and moderate exacerbations of asthma in adults. Aim: To: (i) compare the effectiveness of doubling existing daily ICS dose (fluticasone) with maintaining usual ICS dose and usual daily ICS dose accompanied by oral steroids (OS) (dexamethasone) during mild and moderately severe exacerbations of asthma in adults; (ii) examine determinants of success and failure; and (iii) compare side-effect profiles. Methods: A randomized, double-blind, placebo-controlled (double-dummy), triple crossover trial. Participants acted as their own control. Outcome measures included treatment success/failure, peak expiratory flow (PEF) after 7 days therapy or at treatment failure, and side-effects. Results: From 22 participants (nine males and 13 females), 18 pairs of data were available for maintaining usual ICS versus doubling ICS and doubling ICS versus OS, and 19 for maintaining usual ICS versus OS. Median (fifth-95th percentile) age was 46.5 (32-64) years and forced expiratory volume in one second (FEV1) 73% (29-97%) predicted. The outcome after doubling ICS was not superior to maintaining usual ICS, with 11 (61%) failures in both arms (P = 0.66). OS, with only 5 (26%) failures, was superior to maintaining usual ICS with 12 (63%) failures (P = 0.04), and to doubling ICS with 5 (28%) versus 11 (61%) failures (P = 0.07). Median PEF (as percentage of run-in best) at end-points were 90.5% (57.1-177.1) for OS, 78.3% (39.5-103.1) for maintaining usual ICS and 77.9 (27.7-110.3) for doubling ICS. Neither gender nor PEF at exacerbation were predictive of failure. Although doubling ICS was not an effective therapy overall, ICS dose at exacerbation were predictive of success in the doubling ICS arm (P = 0.04). Treatment failures when doubling daily ICS dose were more common if achieved fluticasone dose was less than 2000 mu g (three of 11, 73%) compared to 2000 mu g or greater (eight of eight, 37.5%). Increasing age and the presence of an upper respiratory tract infection (URTI) were predictive of failure with OS. Side-effects were more commonly reported with OS (52.6%) than doubling ICS (42.1%) or maintaining usual ICS (19.1%) with the most common being mood changes (36.8%), sleep disturbance (31.6%) and changes in appetite (26.3%). Conclusions: Doubling daily ICS dose per se is not effective for the treatment of mild to moderately severe exacerbations of asthma in adults. Success may depend on achieved ICS dose. Oral steroids are effective, but side-effects are common. A review of current guidelines may be warranted.

Multiphoton ac Stark effect in a bichromatically driven two-level atom

We study the interaction of a two-level atom with two lasers of different frequencies and amplitudes: a strong laser of Rabi frequency 2 Ohm(1) on resonance with the atomic transition, and a weaker laser detuned by subharmonics (2 Ohm(1)/n) of the Rabi frequency of the first. We find that under these conditions the second laser couples the dressed states created by the first in an n-photon process, resulting in doubly dressed states and in a ''multiphoton ac Stark'' effect. We calculate the eigenstates of the doubly dressed atom and their energies, and illustrate the role of this multiphoton ac Stark effect in its fluorescence, absorption, and Autler-Townes spectra. [S1050-2947(98)07607-0].

Geochemical mass-balance and oxygen-isotope constrains on silcrete formation and its paleoclimatic implications in Southern Australia

Two geographically distinct silcrete associations are present in southern Australia, inland and eastern; these were sampled in central South Australia and central Victoria, respectively, At each site, both silicified and immediately adjacent unsilicified parent material were collected. Analytical data from these pairs were used to construct isocons, assuming Zr immobility, and to calculate the volume change and amount of silica introduced during silicification, These results, together with whole-rock oxygen isotope compositions, were used to determine the delta(18)O of th, introduced silica, The results show that the eastern silcretes in central Victoria are probably linked genetically to the associated basalts, weathering of which supplied the introduced silica, This conclusion is based on the close spatial connection between the two, as well as the substantial amount of introduced silica in the silcretes (greater than in the inland silcretes), resulting in volume increases in some eastern silcretes, Oxygen isotopic calculations for the silcretes indicate that the silica precipitated from groundwaters at temperatures slightly higher than present conditions. Silcrete formation apparently occurred during the Miocene and Pliocene (basalts in Victoria younger than Pliocene lack associated silcrete) and may reflect the much wetter climate in southeastern Australia at that time. The inland silcretes of central South Australia can be divided into pedogenic (the most common) and groundwater varieties. The pedogenic silcretes, which show typical soil features like columnar and nodular textures, contain moderate amounts of introduced silica that precipitated by evaporation from saline groundwaters, For the groundwater silcretes, which have massive textures and formed at or close to the water table, insufficient data are available to determine the mode of formation. The inland pedogenic silcretes have probably been farming from the Eocene-Miocene to the present, implying that conditions of seasonally high evaporation have occurred in central Australia during this time period. Thus silcrete formation depends on a complex interplay between climate and silica supply, and it is impossible to generalize that the presence of silcrete is indicative of a particular climate. Likewise, the elemental composition of silcretes, particularly Ti content, is not necessarily of climatic significance, Nevertheless, detailed geochemical and oxygen isotopic studies of a silcrete and its parent material can elucidate the mechanisms of silcrete formation, and if evaporation is indicated as a major factor in silcrete formation, then the climate at the time was likely to have been at least seasonally arid.

Effect of sodium dodecylbenzene sulfonate on the motion of three-phase contact lines on the Wilhelmy plate surface

The combined approach of the molecular-kinetic and hydrodynamic theories for description of the motion of three-phase gas-liquid-solid contact lines has been examined using the Wilhelmy plate method. The whole dynamic meniscus has been divided into molecular, hydrodynamic, and static-like regions. The Young-Laplace equation and the molecular-kinetic and hydrodynamic dewetting theories have been applied to describe the meniscus profiles and contact angle. The dissipative forces accompanying the dynamic dewetting have also been investigated. The experiments with a Wilhelmy plate made from an acrylic polymer sheet were carried out using a computerized apparatus for contact angle analysis (OCA 20, DataPhysics, Germany). The extrapolated dynamic contact angle versus velocity of the three-phase contact line for Milli-Q water and 5 x 10(-4) M SDBS solution was experimentally obtained and compared with the combined MHD models with low and moderate Reynolds numbers. The models predict similar results for the extrapolated contact angle. SDBS decreases the equilibrium contact angle and increases the molecular jumping length but does not affect the molecular frequency significantly. The hydrodynamic deformation of the meniscus, viscous dissipation, and friction were also influenced by the SDBS surfactant. (c) 2005 Elsevier Inc. All rights reserved.

Effect of Fusobacterium nucleatum on the T and B cell responses to Porphyromonas gingivalis in a mouse model

T cell cytokine profiles and specific serum antibody levels in five groups of BALB/c mice immunized with saline alone, viable Fusobacterium nucleatum ATCC 25586, viable Porphyromonas gingivalis ATCC 33277, F. nucleatum followed by P. gingivalis and P. gingivalis followed by F nucleatum were determined. Splenic CD4 and CD8 cells were examined for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma and IL-10 by dual colour flow cytometry and the levels of serum anti-F. nucleatum and anti-P. gingivalis antibodies determined by an ELISA. Both Th1 and Th2 responses were demonstrated by all groups, and while there were slightly lower percentages of cytokine positive T cells in mice injected with F. nucleatum alone compared with the other groups immunized with bacteria., F nucleatum had no effect on the T cell production of cytokines induced by P gingivalis in the two groups immunized with both organisms. However, the percentages of cytokine positive CD8 cells were generally significantly higher than those of the CD4 cells. Mice immunized with F nucleatum alone had high levels of serum anti-E nucleatum antibodies with very low levels of P. gingivalis antibodies, whereas mice injected with P gingivalis alone produced anti-P. gingivalis antibodies predominantly. Although the levels of anti-E nucleatum antibodies in mice injected with E nucleatum followed by P. gingivalis were the same as in mice immunized with F nucleatum alone, antibody levels to P. gingivalis were very low. In contrast, mice injected with P. gingivalis followed by F nucleatum produced equal levels of both anti-P. gingivalis and anti-F nucleatum antibodies, although at lower levels than the other three groups immunized with bacteria, respectively. Anti-Actinobacillus actitiomycetemcomitans, Bacteroides forsythus and Prevotella intermedia serum antibody levels were also determined and found to be negligible. In conclusion, F nucleatum immunization does not affect the splenic T cell cytokine response to P. gingivalis. However, F nucleatum immunization prior to that of P. gingivalis almost completely inhibited the production of anti-P gingivalis antibodies while P. gingivalis injection before F. nucleatum demonstrated a partial inhibitory effect by P. gingivalis on antibody production to F. nucleatum. The significance of these results with respect to human periodontal disease is difficult to determine. However, they may explain in part differing responses to P. gingivalis in different individuals who may or may not have had prior exposure to F. nucleatum. Finally, the results suggested that P. gingivalis and F. nucleatum do not induce the production of cross-reactive antibodies to other oral microorganisms.

On the effect of tracer density on axial dispersion in a batch oscillatory baffled column

In this paper, we report our modelling evaluation on the effect of tracer density on axial dispersion in a batch oscillatory baffled column (OBC). Tracer solution of potassium nitrite, its specific density ranged from 1.0 to 1.5, was used in the study, and was injected to the vertical column from either the top or bottom. Local concentration profiles are measured using conductivity probes at two locations along the height of the column. Using the experimental measured concentration profiles together with both 'Tank-in-Series' and 'Plug Flow with Axial Dispersion' models, axial dispersion coefficients were determined and used to describe the effect of specific tracer density on mixing in the OBC. The results showed that the axial dispersion coefficients evaluated by the two models are very similar in both magnitudes and trends, and the range of variations in such coefficients is generally larger for the bottom injection than for the top one. Empirical correlations linking the mechanical energy for mixing, the specific density of tracer and axial dispersion coefficient were established. Using these correlations, we identified the enhancements of up to 269% on axial dispersion for various specific tracer densities. (C) 2002 Elsevier Science B.V. All rights reserved.

Physiological profiles of restricted endemic plants and their widespread congenors in the North Queensland wet tropics, Australia

Little is known about causes of endemic rarity in plants. This study pioneered an approach that determined environmental variables in the rainforest habitat and generated physiological profiles for light, water, and nutrient relations for three endemically restricted versus widespread congeneric species' pairs. We found no overall consistent differences in the physiological variables between the group of restricted species and the group of widespread species, and congeneric species pairs were therefore examined individually. Availability of soil nutrients did not differ between restricted-widespread species sites suggesting that species grow under comparable nutrient conditions. Under ambient and manipulated higher light conditions, widespread Gardenia ovularis had a greater photosynthetic activity than restricted Gardenia actinocarpa suggesting that the two species differ in their photosynthetic abilities. Differences between Xanthostemon species included lower photosynthetic activity, higher transpiration rate, and a higher foliar manganese concentration in restricted Xanthostemon formosus compared to widespread Xanthostemon chrysanthus. It is suggested that X. formosus is restricted by its high water use to its current rainforest creek edge habitat, while X. chrysanthus grows in a range of environments, although naturally found in riparian rainforest. Restricted Archidendron kanisii had higher electron transport rates, greater dissipative capacity for removal of excess light, and more efficient investment of nitrogen into photosynthetic components, than its widespread relative Archidendron whitei. These observations and previous research suggest that restricted Archidendron kanisii is in the process of expanding its range. Physiological profiles suggest a different cause of rarity for each species. This has implications for the conservation strategies required for each species. (C) 2002 Elsevier Science Ltd. All rights reserved.

N-Substituent effect of maleimides on acrylate polymerization initiated by three-component systems

In this paper, the relative photopolymerization efficiency for polymerization of a difunctional acrylate initiated by various N-substituted maleimides in the presence of amine and benzophenone are compared on the basis of a photo-differential scanning calorimetry (photo-DSC) study. The trends in the polymerization rates were obtained from the photopolymerization profiles and expressed in terms of a photoinitiation index, I-p. An N-substituent index, I-s, which indicates whether each N-substituent plays either a positive (when I-s > 1) or a negative (when I-s < 1) role in the initiation process relative to MI (unsubstituted maleimide), was determined. (C) 2003 Society of Chemical Industry.

Using the effect size to model change in preference values from descriptive health status

Objectives: This pilot study describes a modelling approach to translate group-level changes in health status into changes in preference values, by using the effect size (ES) to summarize group-level improvement. Methods: ESs are the standardized mean difference between treatment groups in standard deviation (SD) units. Vignettes depicting varying severity in SD decrements on the SF-12 mental health summary scale, with corresponding symptom severity profiles, were valued by a convenience sample of general practitioners (n = 42) using the rating scale (RS) and time trade-off methods. Translation factors between ES differences and change in preference value were developed for five mental disorders, such that ES from published meta-analyses could be transformed into predicted changes in preference values. Results: An ES difference in health status was associated with an average 0.171-0.204 difference in preference value using the RS, and 0.104-0.158 using the time trade off. Conclusions: This observed relationship may be particular to the specific versions of the measures employed in the present study. With further development using different raters and preference measures, this approach may expand the evidence base available for modelling preference change for economic analyses from existing data.

Diffusion modeling of percutaneous absorption kinetics: 3. Variable diffusion and partition coefficients, consequences for stratum corneum depth profiles and desorption kinetics

Stratum corneum (SC) desorption experiments have yielded higher calculated steady-state fluxes than those obtained by epidermal penetration studies. A possible explanation of this result is a variable diffusion or partition coefficient across the SC. We therefore developed the diffusion model for percutaneous penetration and desorption to study the effects of either a variable diffusion coefficient or variable partition coefficient in the SC over the diffusion path length. Steady-state flux, lag time, and mean desorption time were obtained from Laplace domain solutions. Numerical inversion of the Laplace domain solutions was used for simulations of solute concentration-distance and amount penetrated (desorbed)-time profiles. Diffusion and partition coefficients heterogeneity were examined using six different models. The effect of heterogeneity on predicted flux from desorption studies was compared with that obtained in permeation studies. Partition coefficient heterogeneity had a more profound effect on predicted fluxes than diffusion coefficient heterogeneity. Concentration-distance profiles show even larger dependence on heterogeneity, which is consistent with experimental tape-stripping data reported for clobetasol propionate and other solutes. The clobetasol propionate tape-stripping data were most consistent with the partition coefficient decreasing exponentially for half the SC and then becoming a constant for the remaining SC. (C) 2004 Wiley-Liss, Inc.

Genetic variation for carbon isotope discrimination in sunflower: Association with transpiration efficiency and evidence for cytoplasmic inheritance

Plants accumulate isotopes of carbon at different rates because of discrimination against C-13 relative to C-12. In plants that fix carbon by the C-3 pathway, the amount of discrimination correlates negatively with transpiration efficiency (TE) where TE is the amount of dry matter accumulated per unit water transpired. Therefore, carbon isotope discrimination (Delta) has become a useful tool for selecting genotypes with improved TE and performance in dry environments. Surveys of 161 sunflower (Helianthus spp.) genotypes of diverse origin revealed a large and unprecedented range of genetic variation for Delta (19.5-23.8parts per thousand). A strong negative genetic correlation (r(g)) between TE and Delta (r(g) = -0.87, P < 0.001) was observed in glasshouse studies. Gas exchange measurements of field grown plants indicated that Delta was strongly correlated with stomatal conductance to water vapor (g), (r(g) 0.64, P < 0.01), and the ratio of net assimilation rate (A) to g, (r(g) = 0.86, P < 0.001), an instantaneous measure of TE. Genotype CMSHA89MAX1 had the lowest TE (and highest Delta) of all genotypes tested in these studies and low yields in hybrid combination. Backcrossing studies showed that the TE of this genotype was due to an adverse effect of the MAX1 cytoplasm, which was inherited from the diploid perennial H. maximiliani Schrader. Overall, these studies suggested that there is an excellent opportunity for breeders to develop sunflower germplasm with improved TE. This can be achieved, in part, by avoiding cytoplasms such as the MAX1 cytoplasm.

The effect of ionic strength variation and anion competition on the development of nitrate accumulations in variable charge subsoils

The leaching of N fertilisers has led to the formation of nitrate (NO3) accumulations in deep subsoils (>5 m depth) of the Johnstone River catchment. This paper outlines the chemical mechanism by which these NO3 accumulations are formed and maintained. This was achieved via a series of column experiments designed to investigate NO3 leaching in relation to the soil charge chemistry and the competition of anions for exchange sites. The presence of variable charge minerals has led to the formation positive surface charge within these profiles. An increase in the soil solution ionic strength accompanying the fertiliser leaching front acts to increase the positive (and negative) charge density, thus providing adsorption sites for NO3. A decrease in the soil solution ionic strength occurs after the fertiliser pulse moves past a point in the profile, due to dilution with incoming rainwater. Nitrate is then released from the exchange back into the soil solution, thus buffering the decrease in the soil solution ionic strength. Since NO3 was adsorbed throughout the profile in this experiment it does not effectively explain the situation occurring in the field. Previous observations of the sulfate (SO4) profile distribution indicated that large SO4 accumulations in the upper profile may influence the NO3 distribution through competition for adsorption sites. A subsequent experiment investigating the effect of SO4 additions on NO3 leaching showed that NO3 adsorption was minimal in the upper profile. Adsorption of NO3 did occur, though only in the region of the profile where SO4 occupancy was low, i.e. in the lower profile. Therefore, the formation of the NO3 accumulations is dependent on the variable charge mineralogy, the variation of charge density with soil solution ionic strength, and the effects of SO4 competition for adsorption sites.

Quantum effect induced reverse kinetic molecular sieving in microporous materials

We report kinetic molecular sieving of hydrogen and deuterium in zeolite rho at low temperatures, using atomistic molecular dynamics simulations incorporating quantum effects via the Feynman-Hibbs approach. We find that diffusivities of confined molecules decrease when quantum effects are considered, in contrast with bulk fluids which show an increase. Indeed, at low temperatures, a reverse kinetic sieving effect is demonstrated in which the heavier isotope, deuterium, diffuses faster than hydrogen. At 65 K, the flux selectivity is as high as 46, indicating a good potential for isotope separation.

Effect on trend estimates of the difference between survey respondents and non-respondents: Results from 27 populations in the WHO MONIICA Project

Introduction: In the World Health Organization (WHO) MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) Project considerable effort was made to obtain basic data on non-respondents to community based surveys of cardiovascular risk factors. The first purpose of this paper is to examine differences in socio-economic and health profiles among respondents and non-respondents. The second purpose is to investigate the effect of non-response on estimates of trends. Methods:Socio-economic and health profile between respondents and non-respondents in the WHO MONICA Project final survey were compared. The potential effect of non-response on the trend estimates between the initial survey and final survey approximately ten years later was investigated using both MONICA data and hypothetical data. Results: In most of the populations, non-respondents were more likely to be single, less well educated, and had poorer lifestyles and health profiles than respondents. As an example of the consequences, temporal trends in prevalence of daily smokers are shown to be overestimated in most populations if they were based only on data from respondents. Conclusions: The socio-economic and health profiles of respondents and non-respondents differed fairly consistently across 27 populations. Hence, the estimators of population trends based on respondent data are likely to be biased. Declining response rates therefore pose a threat to the accuracy of estimates of risk factor trends in many countries.