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S-wave predominance of epicardial electrograms during atrial fibrillation in humans: indirect evidence for a role of the thin subepicardial layer.

OBJECTIVES: The purpose of this study was to characterize the morphology of fibrillation electrograms in patients in order to provide insight into the underlying electropathologic substrate of atrial fibrillation (AF). BACKGROUND: Electrograms recorded during AF show a high degree of spatiotemporal variation. METHODS: AF was induced by rapid atrial pacing in 25 patients undergoing cardiac surgery. A unipolar mapping array of 244 electrodes was positioned on the free wall of the right atrium to record multiple epicardial fibrillation electrograms. Local anisotropy in conduction and epicardial wavefront curvature during AF were determined by fitting the best quadratic surface on the activation times of rectangular areas of 3 x 3 electrodes. RESULTS: During AF, unipolar epicardial electrograms revealed a clear predominance of S waves. The average RS difference during type I and II AF was -0.15 +/- 0.08 and -0.22 +/- 0.08. During type III AF, the predominance of S waves was less prominent (-0.07 +/- 0.05; P < .005). In all types of AF, the degree of anisotropy in conduction was remarkably low (anisotropy ratio: 1.24 +/- 0.09), and no clear directional effect on the relative amplitude of R and S waves was found. There was a weak relationship between local curvature of wavefronts and RS difference (r = 0.23; P < .01). Computer simulations showed that the negative RS difference could result from transmural activation in an epicardial to endocardial direction. CONCLUSIONS: The clear predominance of S waves in epicardial fibrillation electrograms is not due to anisotropy and can only be partly explained by a high curvature of fibrillation waves. Predominant epicardial to endocardial activation seems to be important in producing rS electrograms on the epicardium. This finding provides indirect evidence that the thin epicardial layer of atrial myocardium plays an important role in propagation of fibrillation waves.

Adult↗

Automatic mapping of human atrial fibrillation by template matching.

BACKGROUND: The high spatiotemporal variation in morphology of fibrillation electrograms makes mapping of atrial fibrillation (AF) a difficult and burdensome task. OBJECTIVES: The purpose of this study was to evaluate the results of automatic detection of fibrillation electrograms by a template matching technique. METHODS: During cardiac surgery in 25 patients without a history of AF, paroxysms of AF were induced by rapid atrial pacing. A mapping array of 244 unipolar electrodes (3.6-cm diameter, 2.25-mm interelectrode distance) was positioned on the free wall of the right atrium. All fibrillation electrograms were correlated with a mathematically constructed library of 128 potentials of different duration, RS ratio, and short double components. The moments of maximal correlation, coinciding with the negative deflection in the fibrillation potentials, were used to create fibrillation maps. RESULTS: In each patient, a segment of 18.6 +/- 3.8 seconds of AF was analyzed, resulting in 80 to 130 maps per patient. The output of the automatic algorithm was compared with careful manual analysis by an experienced investigator. Of the total database of 398,796 fibrillation potentials, 93.6% +/- 4.2% resulted in a good correlation with one of the templates in the library (correlation coefficient >= 0.7). At a correlation threshold of 0.6, on average template matching yielded slightly more false-positive than false-negative detections (sensitivity 96.6% +/- 2.5%, positive predictive value 94.3% +/- 5.4%). The majority of false-positive detections were due to electrotonic potentials recorded along the lateral boundaries of the fibrillation waves. This led to a slight overlap of fibrillation waves but not to false detection of nonexisting wavefronts. Undersensing was mainly due to the presence of long double and fractionated potentials (2.6%) that were not represented in the template library. Fractionated parts in the electrograms were identified by failure of template matching and can be analyzed separately. CONCLUSION: Template matching is a useful technique for characterizing unipolar fibrillation electrograms and for visualizing the complex activation patterns during AF. It allows automatic evaluation of the electropathologic substrate of AF on an individual basis.

Adult↗

The attentional blink in space and time.

We report the results of two experiments addressing spatiotemporal variations in the "attentional blink" (AB). In the first experiment, six streams of letters were presented simultaneously around a circle on a screen. The identity of the letters changed every 140 ms. The task was to identify two target digits (T1 and T2) that could appear in any of the streams with a variable time lag between the two. The results show that the AB is not constant across space and that following the allocation of attention to a certain location (the location of T1), discrimination can be better at locations quite far away from T1, than at locations closest to T1. Furthermore, performance at the farthest locations seemed to recover sooner from the AB than locations closer to where T1 appeared. Similar results were obtained in a second experiment where observers performed a cued discrimination task. The results accord well with the proposal that there is a region around the attended site (the center of attention) where attentional resolution is particularly poor, worse than at sites further away from the attended one. We propose that this reflects lateral inhibition of neurons responsive to the region around the attended site, with the goal of suppressing potentially distracting or interfering information.

Adult↗

Orientation opponency in human vision revealed by energy-frequency analysis.

Studies of second-order visual processing have primarily been concerned with understanding the mechanisms for detecting spatiotemporal variations in such attributes as contrast, orientation, spatial frequency, etc. Here, we have examined the orientation characteristics of second-order processes using bandpass noise whose Fourier energy is sinusoidally modulated across orientation, rather than across space or time. Sensitivity for detecting orientation-energy modulations was measured as a function of modulation frequency. The sensitivity function was bandpass, with a pronounced peak at an orientation frequency of 4 cycles/pi. An inverse Fourier transform of the sensitivity function revealed a filter profile displaying a centre-surround antagonism across orientation, with an excitatory centre within 6-9 deg and inhibitory lobes at 15-20 deg from the filter's centre. The degree of centre-surround antagonism increased with stimulus size far beyond the spatial range of the first-order filters (more than 64 times the dominant spatial wavelength of the noise carrier). These results suggest that second-order processing involves 'orientation-opponent' channels that extract differences in first-order outputs across orientation over a wide area of the visual field.

Contrast Sensitivity↗

Spatiotemporal regulation of hnRNP M and 2H9 gene expression during mouse embryonic development.

Using the HeLa cell model along with an in vitro splicing system, we have previously shown that hnRNP M and 2H9 are involved in the pre-mRNA splicing process and most interestingly also in heat shock-induced transient splicing arrest by transiently leaving the hnRNP complexes. Due to this unique regulatory function in a mechanism that turns splicing on and off, these two hnRNPs appear as important proteins for controlling gene expression. Here we investigated by in situ hybridization and immunohistochemical staining techniques the expression level of specific mRNA and protein during mouse embryonic development. HnRNP M and 2H9 are found to be expressed at all examined stages (6.5-18.5 days post-coïtum), in a differential manner, and at various levels depending on tissues, cell types and also embryonic stages; fairly high levels of both hnRNPs are always observed in the central nervous system. Furthermore, levels of colocalizing protein and transcript are not always present in the same proportion, thus suggesting a post-transcriptional regulation of hnRNP M and 2H9 gene expression. The complex spatiotemporal variations we observed might well anticipate a role for these two hnRNPs also in modulating splicing, thereby influencing gene expression and further many physiological processes.

Animals↗

System dynamics of subcellular transport.

In pharmacokinetic experiments, interpretations often hinge on treating cells as a "black box": a single, lumped compartment or boundary. Here, a combinatorial library of fluorescent small molecules was used to visualize subcellular transport pathways in living cells, using a kinetic, high content imaging system to monitor spatiotemporal variations of intracellular probe distribution. Most probes accumulate in cytoplasmic vesicles and probe kinetics conform to a nested, two-compartment dynamical system. At steady state, probes preferentially partition from the extracellular medium to the cytosol, and from the cytosol to cytoplasmic vesicles, with hydrophobic molecules favoring sequestration. Altogether, these results point to a general organizing principle underlying the system dynamics of subcellular, small molecule transport. In addition to plasma membrane permeability, subcellular transport phenomena can determine the active concentration of small molecules in the cytosol and the efflux of small molecules from cells. Fundamentally, direct observation of intracellular probe distribution challenges the simple boundary model of classical pharmacokinetics, which considers cells as static permeability barriers.

4-Chloro-7-nitrobenzofurazan↗

Stream phosphorus transport in the Lake Tahoe basin, 1989-1996.

Lake Tahoe is undergoing the initial stages of cultural eutrophication due to human alteration of the airshed and watershed. The lake's switch from nitrogen (N) to phosphorus (P) limitation has been attributed primarily to atmospheric N loading. This places an increased importance on controlling watershed movement of P to the lake. A stream water quality monitoring data set consisting of nine streams in the Lake Tahoe basin has been analyzed to characterize the spatiotemporal variation of P delivery to the lake. This data is from the Lake Tahoe Interagency Monitoring Program (LTIMP), which provides scientific data for planning and regulatory agencies to address environmental problems in the Lake Tahoe basin. Results indicate that P delivery (concentrations, loads) varies greatly at interannual, seasonal, and spatial scales. Annual and seasonal total P (TP) concentrations can vary up to three orders of magnitude in a given stream and are strongly associated with suspended sediment. Particulate P is the major form of P transported by Tahoe streams and was strongly correlated with percent surficial geologic deposits, which are primarily located near streams. Tahoe streams with the highest annual P concentrations often had the lowest annual P loads, and visa versa. P loading is greatest during the spring snowmelt (75% of annual average). Potential watershed parameters influencing P delivery to Lake Tahoe have been identified as precipitation, basin area, basin steepness, and road and human development coverage. Results also suggest that human development impacts on stream P loads are most prevalent during high precipitation years. Identification and quantification of stream sediment and P sources such as streambanks and impervious surface is necessary to aid in watershed restoration efforts.

Eutrophication↗

Efficient mapping of California mortality fields at different spatial scales.

A meaningful characterization of epidemiologic fields (mortality, incidence rate, etc.) often involves the assessment of their spatiotemporal variation at multiple scales. An adequate analysis should depend on the scale at which the epidemiologic field is considered rather than being limited by the scale at which the data are available. In many studies, for example, data are available at a larger scale (say, counties), whereas the epidemiologist is interested in a smaller-scale analysis (say, residential neighborhoods). We propose a mathematically rigorous and epidemiologically meaningful multiscale approach that uses the well-known BME theory to study important scale effects and generate informative scale-dependent maps. The approach is applied to a real-world case study involving daily mortality counts in the state of California. The approach accounts for scale effects and produces mortality predictions at the zip-code scale by downscaling data from the county scale. The multiscale approach is tested by means of a verification data set with detailed mortality information at the zip-code level for 1 day. A measure of mapping accuracy is used to demonstrate that the multiscale approach offers more accurate mortality predictions at the local scale than existing approaches, which do not account for scale effects.

California↗

Microsatellite diversity and genetic structure of fragmented populations of the rare, fire-dependent shrub Grevillea macleayana.

Recent habitat loss and fragmentation superimposed upon ancient patterns of population subdivision are likely to have produced low levels of neutral genetic diversity and marked genetic structure in many plant species. The genetic effects of habitat fragmentation may be most pronounced in species that form small populations, are fully self-compatible and have limited seed dispersal. However, long-lived seed banks, mobile pollinators and long adult lifespans may prevent or delay the accumulation of genetic effects. We studied a rare Australian shrub species, Grevillea macleayana (Proteaceae), that occurs in many small populations, is self-compatible and has restricted seed dispersal. However, it has a relatively long adult lifespan (c. 30 years), a long-lived seed bank that germinates after fire and is pollinated by birds that are numerous and highly mobile. These latter characteristics raise the possibility that populations in the past may have been effectively large and genetically homogeneous. Using six microsatellites, we found that G. macleayana may have relatively low within-population diversity (3.2-4.2 alleles/locus; Hexp = 0.420-0.530), significant population differentiation and moderate genetic structure (FST = 0.218) showing isolation by distance, consistent with historically low gene flow. The frequency distribution of allele sizes suggest that this geographical differentiation is being driven by mutation. We found a lack mutation-drift equilibrium in some populations that is indicative of population bottlenecks. Combined with evidence for large spatiotemporal variation of selfing rates, this suggests that fluctuating population sizes characterize the demography in this species, promoting genetic drift. We argue that natural patterns of pollen and seed dispersal, coupled with the patchy, fire-shaped distribution, may have restricted long-distance gene flow in the past.

Alleles↗

Modeling of automatic capture and focusing of visual attention.

An explanation, based on simple analysis of the spatiotemporal variations of the visual environment, is given to the automatic capture and focusing of visual attention. It is assumed that the transmittance for the sensory signals is modulated by separate control circuits that sample input from the same area of the visual field but at a lower resolution. When these circuits detect significant spatial and/or temporal variations, they "open gates" for the more accurate information arising from the same area. If the variations are related to the spatial resolution, which varies within wide limits over the retina, the visual field is "opened" up to a radius where it captures the most salient structures of the image. If the temporal variations of the signals are further emphasized, the high spatial frequencies begin to dominate. If then the gaze is moved by a small amount, the transmittance of the foveal signal paths is activated strongest.

Animals↗

A localized elevation of cytosolic free calcium is associated with cytokinesis in the zebrafish embryo.

Cytokinesis, a key step in cell division, is known to be precisely regulated both in its timing and location. At present, the regulatory mechanism of cytokinesis is not well understood, although it has been suggested that calcium signaling may play an important role in this process. To test this notion, we introduced a sensitive fluorescent Ca2+ indicator into the zebrafish embryo and used confocal microscopy to measure the spatiotemporal variation of intracellular free Ca2+ concentration ([Ca2+]i) during cell cleavage. It was evident that a localized elevation of [Ca2+]i is closely associated with cytokinesis. First, we found that during cytokinesis, the level of free Ca2+ was elevated locally precisely at the cleavage site. Second, the rise of free Ca2+ was very rapid and occurred just preceding the initiation of furrow contraction. These observations strongly suggest that cytokinesis may be triggered by a calcium signal. In addition, we found that this cytokinesis-associated calcium signal arose mainly from internal stores of Ca2+ rather than from external free Ca2+; it could be blocked by the antagonist of inositol trisphosphate (InsP3) receptors. These findings suggest that the localized elevation of [Ca2+]i is caused by the release of free Ca2+ from the endoplasmic reticulum through the InsP3-regulated calcium channels.

Animals↗

Fibroblast growth factor 2 internal ribosome entry site (IRES) activity ex vivo and in transgenic mice reveals a stringent tissue-specific regulation.

Fibroblast growth factor 2 (FGF-2) is a powerful mitogen involved in proliferation, differentiation, and survival of various cells including neurons. FGF-2 expression is translationally regulated; in particular, the FGF-2 mRNA contains an internal ribosome entry site (IRES) allowing cap-independent translation. Here, we have analyzed FGF-2 IRES tissue specificity ex vivo and in vivo by using a dual luciferase bicistronic vector. This IRES was active in most transiently transfected human and nonhuman cell types, with a higher activity in p53 -/- osteosarcoma and neuroblastoma cell lines. Transgenic mice were generated using bicistronic transgenes with FGF-2 IRES or encephalomyocarditis virus (EMCV) IRES. Measurements of luciferase activity revealed high FGF-2 IRES activity in 11-d-old embryos (E11) but not in the placenta; activity was high in the heart and brain of E16. FGF-2 IRES activity was low in most organs of the adult, but exceptionally high in the brain. Such spatiotemporal variations were not observed with the EMCV IRES. These data, demonstrating the strong tissue specificity of a mammalian IRES in vivo, suggest a pivotal role of translational IRES- dependent activation of FGF-2 expression during embryogenesis and in adult brain. FGF-2 IRES could constitute, thus, a powerful tool for gene transfer in the central nervous system.

Animals↗

Quantitative ecology of ticks as a basis for transmission models of tick-borne pathogens.

Tick population ecology is the basis of spatiotemporal variation in the risk of infection by tick-borne pathogens. The continental distribution of tick-borne encephalitis (TBE) in Europe is statistically associated with a specific pattern of the seasonal dynamics of Ixodes ricinus, and a particular characteristic of the seasonal land surface temperature profile. A tick population model would allow us to move from this statistical analysis to a biological, process-based model for TBE virus and the many other pathogens vectored by Ixodes spp. ticks in Europe and the United States. Long-term field data on I. ricinus are analyzed to provide empirical estimates of rates of the major demographic processes, development, questing, attachment to hosts, and mortality.

Animals↗

Locally constrained mixture representation of dynamic imaging data from PET and MR studies.

Dynamic positron emission tomography (PET) studies provide measurements of the kinetics of radiotracers in living tissue. This is a powerful technology which can play a major role in the study of biological processes, potentially leading to better understanding and treatment of disease. Dynamic PET data relate to complex spatiotemporal processes and its analysis poses significant challenges. In previous work, mixture models that expressed voxel-level PET time course data as a convex linear combination of a finite number of dominant time course characteristics (called sub-TACs) were introduced. This paper extends that mixture model formulation to allow for a weighted combination of scaled sub-TACs and also considers the imposition of local constraints in the number of sub-TACs that can be active at any one voxel. An adaptive 3D scaled segmentation algorithm is developed for model initialization. Increases in the weighted residual sums of squares is used to guide the choice of the number of segments and the number of sub-TACs in the final mixture model. The methodology is applied to five data sets from representative PET imaging studies. The methods are also applicable to other contexts in which dynamic image data are acquired. To illustrate this, data from an echo-planar magnetic resonance (MR) study of cerebral hemodynamics are considered. Our analysis shows little indication of departure from a locally constrained mixture model representation with at most two active components at any voxel. Thus, the primary sources of spatiotemporal variation in representative dynamic PET and MR imaging studies would appear to be accessible to a substantially simplified representation in terms of the generalized locally constrained mixture model introduced.

Algorithms↗

Simultaneous measurement of stomatal conductance, non-photochemical quenching, and photochemical yield of photosystem II in intact leaves by thermal and chlorophyll fluorescence imaging.

A new imaging system capable of simultaneously measuring stomatal conductance and fluorescence parameters, non-photochemical quenching (NPQ) and photochemical yield of photosystem II (Phi(PSII)), in intact leaves under aerobic conditions by both thermal imaging and chlorophyll fluorescence imaging was developed. Changes in distributions of stomatal conductance and fluorescence parameters across Phaseolus vulgaris L. leaves induced by abscisic acid treatment were analyzed. A decrease in stomatal conductance expanded in all directions from the treatment site, then mainly spread along the lateral vein toward the leaf edge, depending on the ABA concentration gradient and the transpiration stream. The relationships between stomatal conductance and fluorescence parameters depended on the actinic light intensity, i.e. NPQ was greater and Phi(PSII) was lower at high light intensity. The fluorescence parameters did not change, regardless of stomatal closure levels at a photosynthetically active photon flux (PPF) of 270 micro mol m(-2) s(-1); however, they drastically changed at PPF values of 350 and 700 micro mol m(-2) s(-1), when the total stomatal conductance decreased to less than 80 and 200 mmol m(-2) s(-1), respectively. This study has, for the first time, quantitatively analyzed relationships between spatiotemporal variations in stomatal conductance and fluorescence parameters in intact leaves under aerobic conditions.

Abscisic Acid↗

Bromomalonic-acid-induced transition from trigger wave to big wave in the Belousov-Zhabotinsky reaction

The Marangoni effects on chemical waves in the ferroin-catalyzed Belousov-Zhabotinsky reaction were studied. The main purpose of the present study was to understand the mechanism of the big wave, an accelerative chemical wave involving surface-tension-driven fluid motions. Spatiotemporal variations of surface tension caused by a chemical wave were measured using the Wilhelmy method. The transition from conventional trigger waves to big waves, due to a concentration change of bromomalonic acid, was observed. The strong surface activity of the bromomalonic acid which was responsible for the transition was also observed. It led to an acceleration of the big waves through the Marangoni effect.

Journal Article↗

Dynamical mechanism for coexistence of dispersing species without trade-offs in spatially extended ecological systems.

Most prior studies on the role of dispersal in the coexistence of competing species have emphasized the need for trade-offs between competitive and colonizing abilities for coexistence. Theoretical studies of the evolution of dispersal recently have revealed an alternative mechanism for the coexistence of species differing solely in dispersal rates in spatially extended systems. We present an analysis and numerical evidence indicating that chaotic synchronism, occurring in an extremely intermittent form, is an important feature of the spatiotemporal variation in fitness required for the coexistence of species without trade-offs.

Animals↗

Noise promotes species diversity in nature.

Species diversity in nature is accomplished by coexistence. In a spatial environment, inferior but rapidly moving species can coexist with superior but relatively stationary species. Recent work showed that chaotic dynamics can provide the spatiotemporal variation in the fitness required for coexistence, via the dynamical mechanism of synchronization and intermittency. Utilizing a realistic model that consists of two interacting species in a two-patch environment, we discovered a stochastic-resonance phenomenon where noise can significantly enhance the coexistence and thereby promote species diversity.

Animals↗