Effects of oxygen consumption in photodynamic therapy (PDT) are considered theoretically and experimentally. A mathematical model of the Type II mechanism of photooxidation is used to compute estimates of the rate of therapy-dependent in vivo oxygen depletion resulting from reactions of singlet oxygen (1O2) with intracellular substrate. Calculations indicate that PDT carried out at incident light intensities of 50 mW/cm2 may consume 3O2 at rates as high as 6-9 microM s-1. An approximate model of oxygen diffusion shows that these consumption rates are large enough to decrease the radius of oxygenated cells around an isolated capillary. Thus, during photoirradiation, cells sufficiently remote from the capillary wall may reside at oxygen tensions that are low enough to preclude or minimize 1O2-mediated damage. This effect is more pronounced at higher power densities and accounts for an enhanced therapeutic response in tumors treated with 360 J/cm2 delivered at 50 mW/cm2 compared to the same light dose delivered at 200 mW/cm2. The analysis further suggests that the oxygen depletion could be partially overcome by fractionating the light delivery. In a transplanted mammary tumor model, a regimen of 30-s exposures followed by 30-s dark periods produced significantly longer delays in tumor growth when compared to the continuous delivery of the same total fluence.
Proton nuclear spin-relaxation studies on water- or oil-saturated granular packings and limestone rocks allow estimating surface molecular dynamical parameters. Measurements were performed at various conditions of temperature, magnetic field strengths, and pore size. We show by low field NMR relaxation that changing the amount of surface paramagnetic impurities leads to striking different pore-size dependences of the relaxation times T1 and T2 of liquids in pores. These dependences are well supported by surface-limited or diffusion-limited relaxation models. Surface relaxivity parameters rho(1) and rho(2) are deduced from the pore-size dependence in the surface-limited regime. We evidence the frequency and temperature dependence of the surface relaxivity rho(1) by field cycling NMR relaxation and relevant theoretical models. The typical frequency dependence found allows an experimental separation of the surface and bulk microdynamics in porous media. Several surface dynamical parameters, such as diffusion coefficients, activation energies, time of residence, and coefficient of surface affinity, were therefore determined. The methods presented here give a powerful analysis of the surface microdynamics of confined liquids, which can be applied to the study of oil-bearing rocks.
Using a new method of xenon laser-polarization that permits the generation of liter quantities of hyperpolarized 129Xe gas, the first 129Xe imaging results from the human chest and the first 129Xe spectroscopy results from the human chest and head have been obtained. With polarization levels of approximately 2%, cross-sectional images of the lung gas-spaces with a voxel volume of 0.9 cm3 (signal-to-noise ratio (SNR), 28) were acquired and three dissolved-phase resonances in spectra from the chest were detected. In spectra from the head, one prominent dissolved-phase resonance, presumably from brain parenchyma, was detected. With anticipated improvements in the 129Xe polarization system, pulse sequences, RF coils, and breathing maneuvers, these results suggest the possibility for 129Xe gas-phase imaging of the lungs with a resolution approaching that of current conventional thoracic proton imaging. Moreover, the results suggest the feasibility of dissolved-phase imaging of both the chest and brain with a resolution similar to that obtained with the gas-phase images.
Summary
1.Many species are adversely affected by human activities at large spatial scales and their conservation requires detailed information on distributions. Intensive ground surveys cannot keep pace with the rate of land-use change over large areas and new methods are needed for regional-scale mapping. 2. We present predictive models for great bustards in central Spain based on readily available advanced very high resolution radiometer (AVHRR) satellite imagery combined with mapped features in the form of geographic information system (GIS) data layers. As AVHRR imagery is coarse-grained, we used a 12-month time series to improve the definition of habitat types. The GIS data comprised measures of proximity to features likely to cause disturbance and a digital terrain model to allow for preference for certain topographies. 3. We used logistic regression to model the above data, including an autologistic term to account for spatial autocorrelation. The results from models were combined using Bayesian integration, and model performance was assessed using receiver operating characteristics plots. 4. Sites occupied by bustards had significantly lower densities of roads, buildings, railways and rivers than randomly selected survey points. Bustards also occurred within a narrower range of elevations and at locations with significantly less variable terrain. 5. Logistic regression analysis showed that roads, buildings, rivers and terrain all contributed significantly to the difference between occupied and random sites. The Bayesian integrated probability model showed an excellent agreement with the original census data and predicted suitable areas not presently occupied. 6. The great bustard's distribution is highly fragmented and vacant habitat patches may occur for a variety of reasons, including the species' very strong fidelity to traditional sites through conspecific attraction. This may limit recolonization of previously occupied sites. 7. We conclude that AVHRR satellite imagery and GIS data sets have potential to map distributions at large spatial scales and could be applied to other species. While models based on imagery alone can provide accurate predictions of bustard habitats at some spatial scales, terrain and human influence are also significant predictors and are needed for finer scale modelling.
The magnetic field and temperature dependence of the water proton nuclear spin-lattice relaxation rate requires that the motion timescale for water molecules in contact with proteins is close to that for pure water at room temperature. Nevertheless, there are a few water molecules, which may be detected by high-resolution, cross-relaxation spectroscopy, that must have relatively long protein-bound lifetimes and that carry the bulk of the relaxation coupling between the protein and the water. The water-protein magnetic coupling affects the interpretation of water relaxation rates in heterogeneous protein systems, such as tissues, and provides new ways to extract useful information about the immobilized components through the effects on the water NMR spectrum. The discussion shows that the conclusions concerning the rapid water molecule motions at the interface are not in conflict with the observations of many water oxygen atom positions in protein crystal structures.
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