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PubMed2002

Spatiotemporal analysis of epizootic raccoon rabies propagation in Connecticut, 1991-1995.

The quantitative analysis of pathogen transmission within its specific spatial context should improve our ability to predict and control the epizootic spread of that disease. We compared two methods for calibrating the effect of local, spatially distributed environmental heterogeneities on disease spread. Using the time-of-first-appearance of raccoon rabies across the 169 townships in Connecticut, we estimated local spatial variation in township-to-township transmission rate using Trend Surface Analysis (TSA) and then compared these estimates with those based on an earlier probabilistic simulation using the same data. Both the probabilistic simulation and the TSA reveal significant reduction in transmission when local spatial domains are separated by rivers. The probabilistic simulation suggested that township-to-township transmission was reduced sevenfold for townships separated by a river. The global effect of this sevenfold reduction is to increase the time-to-first-appearance in the eastern townships of Connecticut by approximately 29.7% (spread was from west to east). TSA revealed a similar effect of rivers with an overall reduction in rate of local propagation due to rivers of approximately 22%. The 7.7% difference in these two estimates reveals slightly different aspects of the spatial dynamics of this epizootic. Together, these two methods can be used to construct an overall picture of the combined effects of local spatial variation in township-to-township transmission on patterns of local rate of propagation at scales larger than the immediate nearest neighboring townships.

Animals↗
PubMed2005

The geographic spread of the CCR5 Delta32 HIV-resistance allele.

The Delta32 mutation at the CCR5 locus is a well-studied example of natural selection acting in humans. The mutation is found principally in Europe and western Asia, with higher frequencies generally in the north. Homozygous carriers of the Delta32 mutation are resistant to HIV-1 infection because the mutation prevents functional expression of the CCR5 chemokine receptor normally used by HIV-1 to enter CD4+ T cells. HIV has emerged only recently, but population genetic data strongly suggest Delta32 has been under intense selection for much of its evolutionary history. To understand how selection and dispersal have interacted during the history of the Delta32 allele, we implemented a spatially explicit model of the spread of Delta32. The model includes the effects of sampling, which we show can give rise to local peaks in observed allele frequencies. In addition, we show that with modest gradients in selection intensity, the origin of the Delta32 allele may be relatively far from the current areas of highest allele frequency. The geographic distribution of the Delta32 allele is consistent with previous reports of a strong selective advantage (>10%) for Delta32 carriers and of dispersal over relatively long distances (>100 km/generation). When selection is assumed to be uniform across Europe and western Asia, we find support for a northern European origin and long-range dispersal consistent with the Viking-mediated dispersal of Delta32 proposed by G. Lucotte and G. Mercier. However, when we allow for gradients in selection intensity, we estimate the origin to be outside of northern Europe and selection intensities to be strongest in the northwest. Our results describe the evolutionary history of the Delta32 allele and establish a general methodology for studying the geographic distribution of selected alleles.

Alleles↗
PubMed1995

[Nuclear medicine methods for the diagnosis of adrenal tumors].

Adrenal scintigraphy using 131I-6-beta-iodomethyl-19-norcholesterol or 6-methyl-75Se-methyl-19-norcholesterol is a function-dependent imaging method which, in association with high-resolution spatial imaging techniques, plays an essential role in the study of adrenocortical hyperfunction. It can distinguish between bilateral cortical hyperplasia and monolateral adenoma or carcinoma and can lateralise the adenoma. In patients with Cushing syndrome, in addition to allowing a distinction to be made between ACTH-dependent forms and independent forms, adrenocortical scintigraphy is particularly appropriate to identify non-common forms of adenomatous hyperplasia. Adrenocortical scintigraphy, performed during dexamethasone administration, is an accurate mean of differentiating bilateral adrenal hyperplasia from monolateral forms (adenoma or carcinoma) in patients with Conn's syndrome. Owing to the gradual spread of high-resolution spatial imaging techniques, the problem of the diagnostic classification of so-called "incidentalomas" (clinically silent masses discovered by chance) is a subject of considerable interest. Adreno-cortical scintigraphy appears to be able to provide an important contribution to identifying the functional behaviour of these tumours. Since the early 80s meta-iodobenzyl-guanidine (MIBG), marked with 131I or 123I, with a structure similar to norepinephrine and characterized by selective tropism for sympathetic and chromaffin tissue, has been used for the scintigraphic study of adrenal medulla. MIBG scintigraphy has been found to be particularly appropriate for the study of intra- and extra-adrenal, single and multiple, benign and malignant pheochromocytomas. This method has a high overall sensitivity and specificity. Lastly, MIBG scintigraphy is useful in the study of neuroblastoma.

3-Iodobenzylguanidine↗
PubMed2003

Distribution of atmospheric SF6 near a large urban area as recorded in the vadose zone.

Local emissions of SF6 are of interest for studying their impact on the use of SF6 as a groundwater-dating tool near source regions as well as for investigating the spatial distributions of (inert) gaseous compounds spreading from urban or industrial centers. A precondition for the use of SF6 in such studies is the capability to document the temporal and spatial evolution of SF6 in and around source regions with sufficient resolution. Here we present a time series of SF6 measurements in soil air at a site (Sparkill, NY) about 25 km north of New York City carried out between May 2000 and January 2002. The data show that, below about 2 m depth, the vadose zone integrates atmospheric SF6 mixing ratios over time scales greater than 1 month. SF6 mixing ratios in soil air at these depths match averaged high-resolution atmospheric measurements performed at Lamont-Doherty Earth Observatory in Palisades, NY, located about 3 km south of Sparkill. To a first-order approximation, a simple one-dimensional diffusion model reproduces the measured SF6 profiles in the vadose zone, suggesting that the soil indeed acts as a low-pass filter for inert atmospheric gases. These findings indicate that measurements of soil air can be used to determine the spatial pattern of SF6 excess relative to the remote atmosphere for a given region. A transect of soil profiles from Manhattan to the tip of Long Island indicates that emissions from sites close to New York City lead to significant SF6 excesses (ca. 25% or more) above the clean air mixing ratios over distances of the order of 80 km.

Air Movements↗
PubMed1992

Activation of protein kinase C blocks astroglial gap junction communication and inhibits the spread of calcium waves.

The following two processes related to astrocytes are thought to depend on intercellular coupling through gap junctions: the spatial buffering of K+o and the spread of calcium waves in the astrocytic syncytium. We have used the following two independent methods to measure the open state of gap junctions: injection of lucifer yellow, and optical calcium imaging of calcium waves in response to probing the cells with a micropipette. The spread of lucifer yellow and calcium waves was inhibited if the cells were treated with either phorbol 12-myristate 13-acetate (PMA) or a synthetic diacylglycerol that activates protein kinase C. Down-regulation of protein kinase C by a 24-h treatment with PMA inhibited the uncoupling effect of PMA, supporting a direct involvement of protein kinase C in the regulation of astroglial gap junctions. Purinergic P2Y receptors, which are coupled to the inositol phospholipid pathway, are expressed by most astroglia in culture. Activation of the P2Y purinergic receptor with the selective agonist 2-methylthio-ATP uncoupled astroglia in a manner similar to the effect of treatment with PMA. Modulation of gap junctional conductance could isolate specific pathways within the astrocytic syncytium to form an extraneuronal information transfer network in brain.

Adenosine Triphosphate↗
PubMed2001

Two competing mechanisms underlying neon color spreading, visual phantoms and grating induction.

Neon color spreading is closely related to the photopic visual phantom illusion, since these two completion phenomena are characterized by in-phase lightness induction, and the only difference in the stimulus configuration is the difference in the inducer height. This idea was supported by the present study. Neon color spreading showed almost the same function of critical spatial frequency as photopic visual phantoms (Experiment 1), and the critical spatial frequency was constant as the inducer height was changed (Experiment 2). We also examined the relationship between neon color spreading and grating induction (characterized by counterphase lightness induction) in critical spatial frequency (Experiment 3) and in magnitudes of lightness induction (Experiment 4) as a function of the inducer height. The inducer height at which in-phase (neon color spreading) appearance gave way to counterphase (grating) induction was approximately 0.1 deg. These results suggest that neon color spreading shares a common neural mechanism with the photopic visual phantom illusion and that this mechanism is different from, and competes with, the mechanism of grating induction.

Color Perception↗
PubMed2004

Calcium imaging of gut activity.

The major cell types regulating gut motility include enteric neurones, interstitial cells of Cajal (ICC) and their effector smooth muscle cells. These cells are arranged conveniently in nested layers through the gut wall. Our knowledge of how many of these cells in each layer are integrated to produce the various patterns of motility is largely unknown. So far, much of our knowledge of gut motility has usually been obtained by examining point sources of activity (e.g. intracellular recordings from enteric neurones, ICC and smooth muscle cells), rather than the spread of activity through these spatially distributed nerve and ICC networks, or smooth muscle syncitia. Our understanding of how these cells are integrated to produce gut movements would be greatly enhanced if we could image the activity in many of these cells in each layer, or many cells in several layers, simultaneously. Calcium (Ca2+) is a major signalling and regulatory molecule in most cells. In fact, electrical excitability in enteric neurones, ICC and smooth muscle is associated with robust rises in intracellular Ca2+ that long outlast the electrical events (e.g. action potentials in neurones and smooth muscle) that gave rise to them. These prolonged Ca2+ responses, together with the development of several high quality Ca2+ indicators, has provided a unique opportunity to image many cells in intact tissues simultaneously using ICCD video-rate cameras along with conventional microscopy. However, confocal microscopy has also been used, and has several advantages over the above systems. These include reduced photo-toxicity and bleaching and the elimination of out of focus light from different layers within the tissue. So far, despite some limitations with the calcium imaging techniques, the spread of activity through the two layers of smooth muscle, ICC networks and myenteric neurones in intact preparations, or cultured myenteric neuronal networks, is beginning to yield exciting new data about how these different cells interact and process information.

Animals↗
PubMed1996

Strong activation of parallel fibers produces localized calcium transients and a form of LTD that spreads to distant synapses.

The temporal and spatial changes in intracellular calcium levels during separate activation of parallel fiber (PF) and climbing fiber (CF) inputs to cerebellar Purkinje cells were studied. PF stimulation (1 Hz), at relatively high stimulus strengths, led to accumulations of calcium that were similar in peak levels to those following CF stimulation but that remained spatially localized. Such stimuli consistently induced a durable depression of PF synaptic transmission that partially occluded further depression by conventional conjunctive stimuli and that was independent of nitric oxide. This depression was accompanied by a reduction of synaptic efficacy in spatially isolated PF inputs to the same cell that was independent of postsynaptic calcium but that was mediated by nitric oxide. These data indicate that LTD comprises at least two separate processes and that parameters of PF stimulation that are capable of raising calcium levels in Purkinje cell dendrites are also able to induce long-term changes in synaptic efficacy.

Animals↗
PubMed2006

Age and gender dependence of human cardiac phosphorus metabolites determined by SLOOP 31P MR spectroscopy.

The aim of this study was to apply (31)P magnetic resonance spectroscopy (MRS) using spatial localization with optimal point spread function (SLOOP) to investigate possible age and gender dependencies of the energy metabolite concentrations in the human heart. Thirty healthy volunteers (18 males and 12 females, 21-67 years old, mean = 40.7 years) were examined with the use of (31)P-MRS on a 1.5 T scanner. Intra- and interobserver variability measures (determined in eight of the volunteers) were both 3.8% for phosphocreatine (PCr), and 4.7% and 8.3%, respectively, for adenosine triphosphate (ATP). High-energy phosphate (HEP) concentrations in mmol/kg wet weight were 9.7 +/- 2.4 (age < 40 years, N = 16) and 7.7 +/- 2.5 (age >or= 40 years, N = 14) for PCr, and 5.1 +/- 1.0 (age < 40 years) and 4.1 +/- 0.8 (age >or= 40 years) for ATP, respectively. Separated by gender, PCr concentrations of 9.2 +/- 2.4 (men, N = 18) and 8.0 +/- 2.8 (women, N = 12) and ATP concentrations of 4.9 +/- 1.0 (men) and 4.2 +/- 0.9 (women) were measured. A significant decrease of PCr and ATP was found for volunteers older than 40 years (P < 0.05), but the differences in metabolic concentrations between both sexes were not significant. In conclusion, age has a minor but still significant impact on cardiac energy metabolism, and no significant gender differences were detected.

Adenosine Triphosphate↗
PubMed2002

On the role of social clusters in the transmission of infectious diseases.

We introduce a spatial stochastic model for the spread of tuberculosis and HIV. We have three parameters: the size of the social cluster for each individual and the infection rates within and outside the social cluster. We show that when the infection rate from outside the cluster is low (this is presumably the case for tuberculosis and HIV) then an epidemic is possible only if the typical social cluster and the within infection rate are large enough. These results may be important in formulating new hypotheses for the transmission of TB and HIV.

Cluster Analysis↗
PubMed2006

Global and local mechanisms of forebrain and midbrain patterning.

During the past years, major advances have been made in understanding the sequential events involved in neural plate patterning. Positional information is already conferred to cells of the neural plate at the time of its induction in the ectoderm. The interplay between the BMP- and the Fgf- signaling pathways leads to the induction of neural cell fates. Thus, neural induction and neural plate patterning are overlapping processes. Later, at the end of gastrulation, positional cell identities within the neural plate are refined and maintained by the action of several neural plate organizers. By locally emitting signaling molecules, they influence the fate of the developing nervous system with high regional specificity. Recent advances have been made both in understanding the mechanisms that dictate the relative position of these organizers and in how signaling molecules spread from them with high spatial and temporal resolution.

Animals↗
PubMed2005

Hemispheric asymmetry in spatial attention across the menstrual cycle.

Functional cerebral asymmetries (FCAs) are known to fluctuate across the menstrual cycle. The mechanisms of these sex hormonal modulations are poorly understood. It has been suggested that gonadal steroid hormones might suppress or specifically activate one hemisphere. However, recent studies suggest that high levels of gonadal steroid hormones reduce FCAs by its modulating effects on cortico-cortical transmission. To investigate the activating effects of gonadal steroid hormones on the interhemispheric interaction, a visual line-bisection task was administered to normally cycling women during menses and the midluteal cycle phase as well as to similar-aged healthy men. The results replicate previous findings of a sex difference in line-bisection as a function of hand-use and show that the hand-use effect fluctuates across the menstrual cycle. High levels of estradiol during the midluteal phase were related to a decrease of the hand-use effect. It is concluded that cycle-related fluctuations in levels of gonadal steroid hormones affect hemispheric asymmetry of spatial attention, presumably by interhemispheric spreading of neuronal activation.

Adult↗
PubMed2002

Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy.

OBJECTIVE: The purpose of the present study was to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in normal, hypertrophied, and failing human heart. BACKGROUND: Conflicting evidence exists on the extent of changes of high-energy phosphate metabolites in hypertrophied and failing human heart. Previous reports using phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) have quantified metabolites in relative terms only. However, this analysis cannot detect simultaneous reductions. METHODS: Four groups of subjects (n = 10 each), were studied: volunteers and patients with hypertensive heart disease (HHD), aortic stenosis, and dilated cardiomyopathy (DCM). Left ventricular (LV) function and mass were measured by cine magnetic resonance imaging. Absolute and relative concentrations of PCr and ATP were determined by (31)P-MRS with spatial localization with optimum point spread function. RESULTS: Left ventricular ejection fraction remained normal in HHD and aortic stenosis, but was severely reduced to 18% in DCM; LV mass was increased by 55%, 79%, and 68% respectively. In volunteers, PCr and ATP concentrations were 8.82 +/- 1.30 mmol/kg wet weight and 5.69 +/- 1.02 mmol/kg wet weight, and the PCr/ATP ratio was 1.59 +/- 0.33. High-energy phosphate levels were unaltered in HHD. In aortic stenosis, PCr was decreased by 28%, whereas ATP remained constant. In DCM, PCr was reduced by 51%, ATP by 35%, and reduction of the PCr/ATP ratio by 25% was of borderline significance (p = 0.06). Significant correlations were observed among energetic and functional variables, with the closest relations for PCr. CONCLUSIONS: In human heart failure due to DCM, both PCr and ATP are significantly reduced. Ratios of PCr to ATP underestimate changes of high-energy phosphate levels.

Adenosine Triphosphate↗
PubMed1994

Okadaic acid disrupts clusters of synaptic vesicles in frog motor nerve terminals.

The fluorophore FM1-43 appears to stain membranes of recycled synaptic vesicles. We used FM1-43 to study mechanisms of synaptic vesicle clustering and mobilization in living frog motor nerve terminals. FM1-43 staining of these terminals produces a linear series of fluorescent spots, each spot marking the cluster of several hundred synaptic vesicles at an active zone. Most agents we tested did not affect staining, but the phosphatase inhibitor okadaic acid (OA) disrupted the fluorescent spots, causing dye to spread throughout the terminal. Consistent with this, electron microscopy showed that vesicle clusters were disrupted by OA treatment. However, dye did not spread passively to a uniform spatial distribution. Instead, time lapse movies showed clear evidence of active dye movements, as if synaptic vesicles were being swept along by an active translocation mechanism. Large dye accumulations sometimes occurred at sites of Schwann cell nuclei. These effects of OA were not significantly affected by pretreatment with colchicine or cytochalasin D. Electrophysiological recordings showed that OA treatment reduced the amount of acetylcholine released in response to nerve stimulation. The results suggest that an increased level of protein phosphorylation induced by OA treatment mobilizes synaptic vesicles and unmasks a powerful vesicle translocation mechanism, which may function normally to distribute synaptic vesicles between active zones.

Animals↗
PubMed2003

Time-series observation of the spreading out of microvessel endothelial cells with atomic force microscopy.

The spreading out of microvessel endothelial cells plays a key role in angiogenesis and the post-injury healing of endothelial cells. In our study, a physical force applied with an atomic force microscopic (AFM) cantilever tip in contact mode partly broke the peripheral adhesion that just-confluent cultured rat cerebral microvessel endothelial cells had formed with basal structures and resulted in the cells actively withdrawing from the stimulated area. Time-series changes in cell extension were imaged using tapping mode AFM, in conjunction with total internal reflection fluorescence microscopy, intensified charge-coupled device and field emission scanning electron microscopy. We also interpreted phase images of living endothelial cells. The results showed that formation of a fibronectin molecule monolayer is key to the spreading out of the cells. Lamellipods as well as filopods would spread out in temporal and spatial distribution following the formation of fibronectin layer. In addition, a lattice-like meshwork of filopods formed in the regions leading lamellipods, which would possibly provide a fulcrum for the filaments of the cytoskeleton within the leading cell body periphery.

Animals↗
PubMed1994

A regional convolution kernel algorithm for scatter correction in dual-energy images: comparison to single-kernel algorithms.

Single kernel scatter correction algorithms are based on the model that the scatter field can be predicted by convolution of the primary intensity (Iprim) with a spatially invariant scatter point-spread function (PSF). Practical limitations (Iprim unknown) suggest the substitution of the total detected intensity (Idet) for Iprim as the source image in the convolution. In regions of high scatter fraction (SF), Idet is a poor approximation of Iprim, thereby causing an overestimation of scatter originating in the region. This contributes to errors in estimating detected scatter in the mediastinum and neighboring regions. A technique using a regionally variable point-spread function that significantly reduces RMS error in estimation of the primary image as compared to the single PSF method is investigated. The regionally variable convolution method employs a larger PSF in the mediastinum and a smaller PSF in the lungs to reduce the error in estimating the scatter throughout the image. The method to allow for patient differences has also been expanded and various implementations of these methods have been compared. Results show that the dual-kernel algorithm is always more effective than an equivalent single-kernel algorithm. The dual-kernel algorithm using a predicted scatter fraction curve gives an overall RMS error in the primary of as low as 20.8% which is equivalent to 8.7% RMS error in the scatter. The dual-kernel method using a predicted scatter fraction curve approaches the accuracy of the single-kernel method using patient specific scatter measurements. Because using individual scatter measurements is a less desirable method for clinical use, we feel that the dual-kernel algorithm which uses two regions specific convolution kernels and a variable scatter fraction curve is the preferable method.

Algorithms↗
PubMed1997

Noninvasive electrocardiographic imaging: reconstruction of epicardial potentials, electrograms, and isochrones and localization of single and multiple electrocardiac events.

BACKGROUND: The goal of noninvasive electrocardiographic imaging (ECGI) is to determine electric activity of the heart by reconstructing maps of epicardial potentials, excitation times (isochrones), and electrograms from data measured on the body surface. METHODS AND RESULTS: Local electrocardiac events were initiated by pacing a dog heart in a human torso-shaped tank. Body surface potential measurements (384 electrodes) were used to compute epicardial potentials noninvasively. The accuracy of reconstructed epicardial potentials was evaluated by direct comparison to measured ones (134 electrodes). Protocols included pacing from single sites and simultaneously from two sites with various intersite distances. Body surface potentials showed a single minimum for both single- and double-site pacing (intersite distances of 52, 35, and 17 mm). Noninvasively reconstructed epicardial electrograms, potentials, and isochrones closely approximated the measured ones. Single pacing sites were reconstructed to within < or = 10 mm of their measured positions. Dual sites were located accurately and resolved for the above intersite distances. Regions of sparse and crowded isochrones, indicating spatial nonuniformities of epicardial activation spread, were also reconstructed. CONCLUSIONS: The study demonstrates that ECGI can reconstruct epicardial potentials, electrograms, and isochrones over the entire epicardial surface during the cardiac cycle. It can provide detailed information on local activation of the heart noninvasively. Its uses could include localization of cardiac electric events (eg, ectopic foci), characterization of nonuniformities of conduction, characterization of repolarization properties (eg, dispersion), and mapping of dynamically changing arrhythmias (eg, polymorphic VT) on a beat-by-beat basis.

Animals↗
PubMed1988

Early-visual factors in letter confusions.

For the purpose of quantifying models of letter recognition, similarities are often specified in terms of stimulus properties. In this paper, an approach is advocated based on similarities between internal letter representations or internal letter images, i.e. it is argued that optical and retinal factors play a more prominent role in letter confusions than is usually assumed. To illustrate this, letter images were calculated on the basis of earlier experimentally determined point spread functions (Blommaert et al., Spatial Vision 2, 99-115, 1987). Next, data on confusion matrices from Bouma (Vision Res. 11, 459-474, 1971) were taken to evaluate different measures which might be useful for quantifying similarities between internal letter representations. In the analysis of experimental data, Luce's (In: Handbook of Mathematical Psychology, 1963) choice model was used. It was found that if similarities were expressed in terms of differences between image contours, a fair first order approximation of Bouma's experimental results could be formulated (overall correlation coefficient of 0.95). Other measures like correlations between spatial frequency spectra of letter images were found to be less successful. The method used provides a means to relate quantitatively stimulus features and optical and early-visual factors to letter confusions.

Form Perception↗