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Local myocardial glucose uptake is proportional to, but not dependent on blood flow.

In nonischaemic myocardium local deoxyglucose deposition is proportional to local blood flow (y = 0.77x + 0.25 for normalized deoxyglucose deposition and blood flow). The cause for this relationship was evaluated using a mathematical model of (deoxy)glucose metabolism to elucidate whether differences in local deoxyglucose deposition are dependent on local blood flow or whether they reflect differences of the local metabolic rate. The axially distributed model consists of two blood-tissue exchange regions arranged concentrically representing the capillary and the extracapillary regions, the latter being a composite of the endothelial, interstitial and parenchymal cell regions. Exchange between the two model regions is described by a permeability-surface area product, consumption in the extracapillary region is modelled by an intraregional clearance term. Twenty blood-tissue exchange units are arranged as parallel pathways to account for the effects of flow heterogeneity and in series with a single, nonexchanging, large vessel segment (0.1 ml/g). Regional volumes (capillary 0.07 ml/g, extracapillary 0.60 ml/g) and the permeability-surface area product (0.2 ml min-1 g-1) are taken from published sources, the local myocardial blood flow is that determined experimentally (between 0.1 and 2.5 ml min-1 g-1). The only free parameter in the model is the extracapillary clearance term (0.0275-0.102 ml min-1 g-1) which was used to fit the measured tissue radioactivity concentration taking the measured arterial concentration of 3H-deoxyglucose into account. The results obtained indicate that variations in local myocardial blood flow, and hence differences in deoxyglucose supply, can not explain quantitatively the differences in local deoxyglucose deposition. However, differences of the metabolic rate (0.326 versus 0.120 micro;mol min-1 g-1) assumed to occur in parallel to the flow differences (1.26 versus 0.42 ml min-1 g-1) can well explain the different mean deoxyglucose deposition in high and low flow areas. This result supports the view that blood flow heterogeneity in the heart is paralleled by a spatial heterogeneity of glucose metabolism.

Animals↗

Patterns of flow and conduction during early ventricular arrhythmias following coronary arterial occlusion in the dog.

The early ventricular arrhythmias of acute myocardial ischaemia arise against a background of rapid alterations in regional myocardial blood flow and electrophysiological properties. The relation between patterns of flow and epicardial activation has been examined in eight open chest anaesthetised dogs at time of onset of these arrhythmias following a proximal occlusion of the left anterior descending coronary artery. Data were derived from 80 epicardial and endocardial sites within a 4 X 5 cm area of left ventricular free wall and processed utilising a three-dimensional computer plotting program. Mean flow within the ischaemic zone was reduced to 0.27 and 0.24 cm3 x g-1 x min-1 in epicardium and endocardium respectively. Marked epicardial activation delays and fragmentation of conduction were observed confined to areas of flow less than 0.3 cm3 x g-1 x min-1. 74% of endocardial and 71% of epicardial tissue samples within the ischaemic zone derived from this area and analysis of flow distribution between adjacent samples demonstrated spatial heterogeneity of flow. It is suggested that local spatial variability in flow within the central ischaemic region may be a prerequisite for abnormal fractionation of conduction leading to re-entrant excitation at the time of onset of early ventricular arrhythmias.

Animals↗

Growth-sustaining Water Potential Distributions in the Primary Corn Root: A NONCOMPARTMENTED CONTINUUM MODEL.

An equation is derived from transport theory to relate local growth rate to local water potential in an expanding tissue. For a noncompartmented continuum model, the relative elemental growth rate (L) equals the divergence of the tensor product of hydraulic conductivity (K) and the gradient of water potential, psi, i.e. L = big dn tri, open * [K . big dn tri, open psi]. This equation is solved numerically using published values of L and K to show the water potential distribution which can sustain the observed growth pattern in the primary root of Zea mays L. The water potential required to sustain growth decreases from the outside to the inside of the root, and the longitudinal profile shows most negative values near the location of the highest growth rate. A cell originally located near the apex experiences a loss and then a gain in water potential as it is displaced through the growth zone.THE APPROACH DIFFERS FROM PREVIOUS FORMULATIONS IN TWO RESPECTS: the assumption of spatial heterogeneity in growth rate, and the solution for spatial (site-specific) rather than material (cell-specific) values of water potential. The role of air spaces and of components (wall and possibly cytoplasm) of the water-conducting pathway which do not accumulate water remains to be clarified; and, as in earlier work, the most uncertain aspects of the analysis are probably the values for hydraulic conductivity.

Journal Article↗

[Increase of heterogeneities at the interface of decrement conduction in Hodgkin-Huxley model].

Spatial heterogeneity was simulated by a 2-fold increase in either of gNa, gK, g1 in the central part of the fibre. The interval-dependent conduction block was not observed in the cable with normal gNa, while the uniform decrease in gNa along the fibre resulted were the block appearance. Difference in the refractory period of these parts of the fibre were the higher, the lower was gNa. The mechanism of this phenomenon was investigated. The results obtained can be used for understanding the mechanism of post infarction arrhythmias.

Animals↗

Environmental control and limnological impacts of a large recurrent spring bloom in Lake Washington, USA.

A series of statistical analyses were used to identify temporal and spatial patterns in the phytoplankton and nutrient dynamics of Lake Washington, an mesotrophic lake in Washington State (USA). These analyses were based on fortnightly or monthly samples of water temperature, Secchi transparency, ammonium (NH(4)), nitrate (NO(3)), inorganic phosphorus (IP), total nitrogen (TN), total phosphorus (TP), dissolved oxygen (DO), pH and chlorophyll a (chl a) collected during 1995-2000 from 12 stations. Lake Washington has a very consistent and pronounced annual spring diatom bloom which occurs from March to May. During this bloom, epilimnetic chl a concentrations peak on average at 10 microg/L, which is 3 times higher than chl a concentrations typically seen during summer stratified conditions. The spring bloom on average comprised 62% diatoms, 21% chlorophytes and 8% cyanobacteria. During summer stratification, diatoms comprised 26% of the phytoplankton community, chlorophytes 37% and cyanobacteria 25%. Cryptophytes comprised approximately 8% of the community throughout the year. Overall, 6 phytoplankton genera (i.e., Aulacoseira, Fragilaria, Cryptomonas, Asterionella, Stephanodiscus, and Ankistrodesmus) cumulatively accounted for over 50% of the community. These analyses also suggest that the phytoplankton community strongly influences the seasonality of NO(3), IP, DO, pH and water clarity. According to a MANOVA, seasonal fluctuations explained 40% of the total variability for the major parameters, spatial heterogeneity explained 10% of variability, and the seasonal-spatial interaction explained 10% of variability. Distinctive patterns were identified between offshore and inshore sampling stations. The results of our analyses also suggest that spatial variability was substantial, but much smaller than temporal variability.

Environmental Monitoring↗

The use of (micro)-X-ray absorption spectroscopy in cement research.

Long-term predictions on the mobility and the fate of radionuclides and contaminants in cementitious waste repositories require a molecular-level understanding of the geochemical immobilization processes involved. In this study, the use of X-ray absorption spectroscopy (XAS) for chemical speciation of trace elements in cementitious materials will be outlined presenting two examples relevant for nuclear waste management. The first example addresses the use of XAS on powdered cementitious materials to determine the local coordination environment of Sn(IV) bound to calcium silicate hydrates (C-S-H). Sn K-edge XAS data of Sn(IV) doped C-S-H can be rationalized by corner sharing binding of Sn octahedra to Si tetrahedra of the C-S-H structure. XAS was further applied to determine the binding mechanism of Sn(IV) in the complex cement matrix. The second example illustrates the potential of emerging synchrotron-based X-ray micro-probe techniques for elucidating the spatial distribution and the speciation of contaminants in highly heterogeneous cementitious materials at the micro-scale. Micro X-ray fluorescence (XRF) and micro-XAS investigations were carried out on Co(II) doped hardened cement paste. These preliminary investigations reveal a highly heterogeneous spatial Co distribution. The presence of a Co(II)-hydroxide-like phase Co(OH)2 and/or Co-Al layered double hydroxide (Co-Al LDH) or Co-phyllosilicate was observed. Surprisingly, some of the initial Co(II) was partially oxidized and incorporated into a Co(III)O(OH)-like phase or a Co-phyllomanganate.

Construction Materials↗

Modelling the spatial configuration of refuges for a sustainable control of pests: a case study of Bt cotton.

The 'high-dose-refuge' (HDR) strategy is widely recommended by the biotechnology industry and regulatory authorities to delay pest adaptation to transgenic crops that produce Bacillus thuringiensis (Bt) toxins. This involves cultivating nontoxic plants (refuges) in close proximity to crops producing a high dose of Bt toxin. The principal cost associated with this strategy is due to yield losses suffered by farmers growing unprotected, refuge plants. Using a population genetic model of selection in a spatially heterogeneous environment, we show the existence of an optimal spatial configuration of refuges that could prevent the evolution of resistance whilst reducing the use of costly refuges. In particular, the sustainable control of pests is achievable with the use of more aggregated distributions of nontransgenic plants and transgenic plants producing lower doses of toxin. The HDR strategy is thus suboptimal within the context of sustainable agricultural development.

Bacillus thuringiensis↗

Computational probes of molecular motion in the Lewis-Wahnstrom model for ortho-terphenyl.

We use molecular dynamics simulations to investigate translational and rotational diffusion in a rigid three-site model of the fragile glass former ortho-terphenyl, at 260 K< or =T< or =346 K and ambient pressure. An Einstein formulation of rotational motion is presented, which supplements the commonly used Debye model. The latter is shown to break down at supercooled temperatures as the mechanism of molecular reorientation changes from small random steps to large infrequent orientational jumps. We find that the model system exhibits non-Gaussian behavior in translational and rotational motion, which strengthens upon supercooling. Examination of particle mobility reveals spatially heterogeneous dynamics in translation and rotation, with a strong spatial correlation between translationally and rotationally mobile particles. Application of the Einstein formalism to the analysis of translation-rotation decoupling results in a trend opposite to that seen in conventional approaches based on the Debye formalism, namely, an enhancement in the effective rate of rotational motion relative to translation upon supercooling.

Journal Article↗

Spatial variation in sensitivity as a factor in measurements of spatial summation of warmth and cold.

Perception of cutaneous heating and cooling depends strongly on stimulus size. Although this dependence has been attributed solely to spatial summation, topographical variations in temperature sensitivity may also play a role. These variations, which differentially affect perception of small stimuli, may have led to overestimation of spatial summation. This possibility was investigated by measuring detection thresholds and perceived intensity for heating and cooling on the volar surface of the forearm using a multiple-thermode stimulus array. By keeping the array in place throughout each testing session we were able to measure threshold sensitivity and suprathreshold responsiveness at eight individual sites and for combinations of these sites having total stimulus areas of 0.64-5.12 cm2. When spatial summation was calculated in the traditional way by averaging the data for all stimuli of each size, the results agreed closely with previous estimates of summation for warmth and cold. When calculations were based instead on the most sensitive test site for each stimulus size, estimates of summation were reduced by about two-thirds. This outcome indicates that the spatial heterogeneity of thermal sensitivity likely contributed to estimates of spatial summation reported in earlier psychophysical studies. A schematic model of cutaneous thermoreception is presented that shows how neural summation and the density of innervation may combine to produce the psychophysical effects of increasing stimulus size (spatial enhancement).

Adult↗

(18)O spatial patterns of vein xylem water, leaf water, and dry matter in cotton leaves.

Three leaf water models (two-pool model, Péclet effect, and string-of-lakes) were assessed for their robustness in predicting leaf water enrichment and its spatial heterogeneity. This was achieved by studying the (18)O spatial patterns of vein xylem water, leaf water, and dry matter in cotton (Gossypium hirsutum) leaves grown at different humidities using new experimental approaches. Vein xylem water was collected from intact transpiring cotton leaves by pressurizing the roots in a pressure chamber, whereas the isotopic content of leaf water was determined without extracting it from fresh leaves with the aid of a purpose-designed leaf punch. Our results indicate that veins have a significant degree of lateral exchange with highly enriched leaf water. Vein xylem water is thus slightly, but progressively enriched in the direction of water flow. Leaf water enrichment is dependent on the relative distances from major veins, with water from the marginal and intercostal regions more enriched and that next to veins and near the leaf base more depleted than the Craig-Gordon modeled enrichment of water at the sites of evaporation. The spatial pattern of leaf water enrichment varies with humidity, as expected from the string-of-lakes model. This pattern is also reflected in leaf dry matter. All three models are realistic, but none could fully account for all of the facets of leaf water enrichment. Our findings acknowledge the presence of capacitance in the ground tissues of vein ribs and highlight the essential need to incorporate Péclet effects into the string-of-lakes model when applying it to leaves.

Algorithms↗

Metabolic heterogeneity in RIF-1 tumours detected in vivo by 31P NMR spectroscopy.

The spatial distribution of phosphate metabolites and pH within subcutaneously implanted RIF-1 tumours was determined by 1-dimensional phosphorus chemical shift imaging. 31P spectra from two to three 4 mm thick cross-sectional slices were obtained for each tumour. Quantitative morphometry was used to estimate the amount of necrosis within those slices. A spatially heterogeneous distribution of phosphate metabolites and pH was detected in most of the tumours. Levels of necrosis ranged from 0-24% for the tumours in this study. There was no significant correlation between the extent of necrosis over this range and levels of metabolites or pH, suggesting that factors besides necrosis can contribute to spectral heterogeneity.

Animals↗

Population dynamics of tuberculosis treatment: mathematical models of the roles of non-compliance and bacterial heterogeneity in the evolution of drug resistance.

SETTING: Patient non-compliance and/or spatial heterogeneity in drug concentration or effectiveness may contribute to the emergence of drug resistance during multiple-drug chemotherapy of tuberculosis. OBJECTIVE: Using mathematical models of mycobacterial population dynamics under antimicrobial treatment, to assess the effects of non-compliance, heterogeneity and other factors on the success of treatment. DESIGN: A mathematical model is used to generate predictions about the ascent of drug resistance in treated hosts with non-compliance and/or a 'protected compartment' of bacteria where only one drug is active; simulations of a more realistic version of this model take into account random mutation, and different assumptions about the size of, and growth rate of bacteria in, the protected compartment. RESULTS: The existence of a protected compartment can increase the likelihood of resistance to the single drug active in that compartment, but only if bacteria resistant to that drug can grow in the protected compartment or if the host is non-adherent to the treatment regimen. However, the protected compartment may also slow the ascent of bacteria resistant to drugs not active in it (e.g. isoniazid) by providing a reservoir of non-selected mycobacteria. The model predicts that relative rates of killing are more important than mutation rates in determining the order in which resistant mutants ascend. Model predictions, in combination with data about drug resistance patterns, suggest that non-compliance, but not heterogeneity, is an important cause of treatment failure. CONCLUSION: Patterns of acquired drug resistance may be used to infer processes of selection during treatment; mathematical models can aid in generating predictions about the relative impacts of treatment parameters in the evolution of resistance, and eventually in suggesting improved treatment protocols.

Antitubercular Agents↗

2H-nuclear magnetic resonance imaging of tumor blood flow: spatial and temporal heterogeneity in a tissue-isolated mammary adenocarcinoma.

2H-Nuclear magnetic resonance imaging of deuteron accumulation in tissue following an i.v. bolus of deuterium oxide provides a noninvasive means of constructing maps of tissue perfusion. With a measured arterial input function and a simple model for tissue-capillary exchange, these data can provide quantitative estimates of local flow. This technique was tested in rat brain and then applied to the study of spatial heterogeneity and temporal variation of blood flow in the tissue-isolated R3230AC mammary adenocarcinoma. Global flow from the brain averaged 0.96 ml/min.g, in good agreement with results obtained from other methods; the perfusion of brain was relatively homogeneous. Global tumor blood flow averaged 0.32 ml/min.g, ranging from 0.11 to 0.96 ml/min.g. Imaging revealed variations in perfusion both within and between the tumors that far exceeded those expected from brain flow heterogeneity and uncertainty in the flow estimates. By obtaining repeated flow images at 30-min intervals, it was possible to show that the regional blood flow shifted with time in single pixels and in multipixel regions. These experiments show that 2H-nuclear magnetic resonance may be useful in obtaining noninvasive and quantitative measurement of temporal blood flow changes in a solid tumor in vivo.

Adenocarcinoma↗

How do grazers affect periphyton heterogeneity in streams?

The effects of grazing by stream invertebrates on algal biomass and spatial heterogeneity were tested experimentally in flow-through microcosms with natural substrates (rocks). One experiment tested the effects of fixed densities of three species of grazers (the caddisfly Allomyia sp. and two mayflies, Epeorus deceptivus and Baetis bicaudatus) on periphyton. Baetis was tested with and without chemical cues from fish predators, which reduced grazer foraging activity to levels similar to the less mobile mayfly (Epeorus). Mean algal biomass (chlorophyll a; chl a) was reduced in grazer treatments compared to ungrazed controls, but there were no differences among grazer treatments. Algal heterogeneity (Morisita index) increased with grazer mobility, with the highest heterogeneity occurring in the Baetis-no fish treatment (most mobile grazer) and the lowest in the caddisfly treatment (most sedentary grazer). A second experiment used a three factorial design, and tested whether initial resource distribution (homogeneous vs. heterogeneous), Baetis density (high vs. low) and fish odor (present vs. absent) affected grazer impact on algal resources. Abundances of Baetis and chl a on individual rocks were recorded to explore the mechanisms responsible for the observed distributions of algae. Initial resource heterogeneity was maintained despite being subjected to grazing. Mean chl a was highest in controls, as in experiment I, and effects of Baetis on algal biomass increased with grazer density. There were no fish effects on algal biomass and no effects of grazer density or fish on algal heterogeneity. At the scale of individual rocks Baetis was unselective when food was homogeneously distributed, but chose high-food rocks when it was heterogeneously distributed. Results of these mechanistic experiments showed that Baetis can track resources at the scale of single rocks; and at moderate densities mobile grazers could potentially maintain periphyton distributions observed in natural streams.

Animals↗

Influence of spatial and temporal heterogeneities on the estimation of demographic parameters in a continuous population using individual microsatellite data.

Drift and migration disequilibrium are very common in animal and plant populations. Yet their impact on methods of estimation of demographic parameters was rarely evaluated especially in complex realistic population models. The effect of such disequilibria on the estimation of demographic parameters depends on the population model, the statistics, and the genetic markers used. Here we considered the estimation of the product Dsigma2 from individual microsatellite data, where D is the density of adults and sigma2 the average squared axial parent-offspring distance in a continuous population evolving under isolation by distance. A coalescence-based simulation algorithm was used to study the effect on Dsigma2 estimation of temporal and spatial fluctuations of demographic parameters. Estimation of present-time Dsigma2 values was found to be robust to temporal changes in dispersal, to density reduction, and to spatial expansions with constant density, even for relatively recent changes (i.e., a few tens of generations ago). By contrast, density increase in the recent past gave Dsigma2 estimations biased largely toward past demographic parameters values. The method was also robust to spatial heterogeneity in density and estimated local demographic parameters when the density is homogenous around the sampling area (e.g., on a surface that equals four times the sampling area). Hence, in the limit of the situations studied in this article, and with the exception of the case of density increase, temporal and spatial fluctuations of demographic parameters appear to have a limited influence on the estimation of local and present-time demographic parameters with the method studied.

Algorithms↗

The spatiotemporal building blocks of X-, Y- and W-ganglion cell receptive fields of the cat's retina.

The spatiotemporal distribution of excitation and inhibition has been characterized in 283 X-, Y- and W- cat retinal ganglion cells. Cells were classified by their latency from optic chiasm stimulation, responses to moving bars and gratings and responses to flashed gratings. As expected from earlier LGN studies the responses of retinal X-cells and Y-cells had distinct spatiotemporal profiles. The Y-cells had a relatively constant or homogeneous spatial distribution of responses while X-cells had a heterogeneous spatial arrangement. As has been previously reported in LGN, retinal X- and Y-fields had four independent spatiotemporal components or response domains; primary excitation (PE), primary inhibition (PI), secondary excitation (SE) and, finally, secondary inhibition (SI). In contrast, W-receptive fields had a few as a single response domain or as many as eight. An unexpected discovery was that all of these W-receptive fields were constructed from spatiotemporal domains, identical to those found in X-receptive fields. Thus, taking on-center and off-center cells into account we have found a total of 16 different spatiotemporal response components or "building blocks" for X- and Y-cells and the X-building blocks appear to be used in the construction of W-receptive fields.

Animals↗

Distribution of sarcomere length and intracellular calcium in mouse skeletal muscle following stretch-induced injury.

1. The effect on sarcomere organization of stretching intact single skeletal muscle fibres by 50% of their optimum length (Lo) during ten consecutive short tetani was investigated. Stretch reduced tetanic force to 36 +/- 4% of the pre-stretch condition. Sarcomere organization was analysed using both electron and confocal microscopy. For confocal microscopy the striation pattern was examined by fluorescently staining F-actin with rhodamine-phalloidin. 2. Electron microscopy revealed that fibres which had been stretched during contraction contained areas of severe sarcomere disorganization, as well as adjacent sarcomeres of normal appearance. 3. Confocal images of stretched fibres, which had been fixed and stained with rhodamine-phalloidin, showed focal regions of overstretched sarcomeres and regions where sarcomeres of adjacent myofibrils were out of alignment with each other. Analysis of all sarcomeres along the length of fibres showed regions of sarcomere inhomogeneity were distributed throughout the fibre length and cross-section. 4. Fibres were microinjected with the fluorescent [Ca2+]i indicator fura-2 before being stretched. Conventional wide-field fluorescence imaging microscopy showed that the tetanic [Ca2+]i was reduced after stretching but remained uniformly distributed. 5. This study confirms the finding that stretch-induced muscle injury has components caused by disorganization of the myofibrillar array and by failure of tetanic Ca2+ release. The structural damage is spatially heterogeneous whereas the changes in Ca2+ release appear to be spatially homogeneous.

Animals↗

Heterogeneity shapes invasion: host size and environment influence susceptibility to a nonnative pathogen.

Theoretical study of invasion dynamics has suggested that spatial heterogeneity should strongly influence the rate and extent of spreading organisms. However, empirical support for this prediction is scant, and the importance of understanding heterogeneity for real-world systems has remained ambiguous. This study quantified the influence of host and environmental heterogeneity on the dynamics of a 19-year disease invasion by the exotic and fatal pathogen, Phytophthora lateralis, within a stream population of its host tree, Port Orford cedar (Chamaecyparis lawsoniana). Using dendrochronology, we reconstructed the invasion history along a 1350-m length of infected stream, which serves as the only route of pathogen dispersal. Contrary to theoretical predictions, the temporal progression of the disease invasion was not related to a host's downstream spatial position, but instead was determined by two sources of heterogeneity: host size and proximity to the stream channel. These sources of heterogeneity influenced both the epidemic and endemic dynamics of this pathogen invasion. This analysis provides empirical support for the influence of heterogeneity on the invasion dynamics of a commercially important forest pathogen and highlights the need to incorporate such natural variability into both invasion theory and methods aimed at controlling future spread.

Animals↗