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PubMed2004

Spatiotemporal resonances in mixing of open viscous fluids.

In this Letter, we reveal a new dynamical phenomenon, called "spatiotemporal resonance," which is expected to take place in a broad range of viscous, periodically forced, open systems. The observation originates from a numerical and theoretical analysis of a micromixer, and is supported by preliminary experimental observations. The theoretical model nicely matches the numerical results, which again is supported by the experiment. Because of the general nature of the phenomenon, this phenomenon is not limited to microsystems. Because of the resonances, a slight tuning of the control parameters makes the mixer enhance the mixing, or suppress it, enhancing interfacial diffusion instead.

Journal Article↗
PubMed2004

Dynamical motifs: building blocks of complex dynamics in sparsely connected random networks.

Spatiotemporal network dynamics is an emergent property of many complex systems that remains poorly understood. We suggest a new approach to its study based on the analysis of dynamical motifs-small subnetworks with periodic and chaotic dynamics. We simulate randomly connected neural networks and, with increasing density of connections, observe the transition from quiescence to periodic and chaotic dynamics. This transition is explained by the appearance of dynamical motifs in the structure of these networks. We also observe domination of periodic dynamics in simulations of spatially distributed networks with local connectivity and explain it by the absence of chaotic and the presence of periodic motifs in their structure.

Brain↗
PubMed2001

Bayesian spatiotemporal inference in functional magnetic resonance imaging.

Mapping of the human brain by means of functional magnetic resonance imaging (fMRI) is an emerging field in cognitive and clinical neuroscience. Current techniques to detect activated areas of the brain mostly proceed in two steps. First, conventional methods of correlation, regression, and time series analysis are used to assess activation by a separate, pixelwise comparison of the fMRI signal time courses to the reference function of a presented stimulus. Spatial aspects caused by correlations between neighboring pixels are considered in a separate second step, if at all. The aim of this article is to present hierarchical Bayesian approaches that allow one to simultaneously incorporate temporal and spatial dependencies between pixels directly in the model formulation. For reasons of computational feasibility, models have to be comparatively parsimonious, without oversimplifying. We introduce parametric and semiparametric spatial and spatiotemporal models that proved appropriate and illustrate their performance applied to visual fMRI data.

Bayes Theorem↗
PubMed1996

A novel family of TEA domain-containing transcription factors with distinct spatiotemporal expression patterns.

We cloned two novel types of TEA domain-containing transcription factor (ETFR-1 and -2) cDNAs. Amino acid sequences deduced for ETFR-1 and -2 as well as those of other known proteins of the same family, TEF-1 and ETF, exhibited significant identity (63-75% overall) to each other not only in the TEA DNA binding domain but also in the C-terminal regions. Northern blot analysis revealed that both the mRNAs were expressed in embryos as well as in many adult tissues, although their levels of expression varied. The results demonstrate that the mammalian TEA domain-containing transcription factor family consists of at least four distinct members, TEF-1, ETF, ETFR-1, and ETFR-2, which exhibit overlapping but differing spatiotemporal expression patterns, suggesting their redundant yet unique roles involved in not only developmental control but also tissue-specific regulation.

Aging↗
PubMed1989

Quantitative analysis of ventral denticular patterns of Drosophila melanogaster larvae and the regulation of the bithorax complex.

A quantitative model of the effect of the bithorax complex on segmentation is presented which could explain the known data of the spatiotemporal regulation of key gene complex during early Drosophila development, in relation to their effects on some of the segmentation landmarks. The model tries to put together the two different genetic levels, the genotypic and the phenotypic. At the genotypic level, a minimal cross-regulatory network of the different genes involved, Antp, Ubx, abd-A and Abd-B which explains the reported levels of expressions of these genes. At the phenotypic level, the pattern of the ventral denticle belts across the larva which are characteristics of the different segments have been compared by calculating a value of the degree of similarity in the case of the wild-type and several mutant combinations. Finally the two parts of the model are combined, showing that a satisfactory agreement between the two can be achieved. Therefore, this work is a first attempt to develop a method which will provide an explanatory solution of the old question in morphogenesis of how the phenotype is directed by the genotype of a cell or organism.

Animals↗
PubMed2005

Spatiotemporal image correlation spectroscopy (STICS) theory, verification, and application to protein velocity mapping in living CHO cells.

We introduce a new extension of image correlation spectroscopy (ICS) and image cross-correlation spectroscopy (ICCS) that relies on complete analysis of both the temporal and spatial correlation lags for intensity fluctuations from a laser-scanning microscopy image series. This new approach allows measurement of both diffusion coefficients and velocity vectors (magnitude and direction) for fluorescently labeled membrane proteins in living cells through monitoring of the time evolution of the full space-time correlation function. By using filtering in Fourier space to remove frequencies associated with immobile components, we are able to measure the protein transport even in the presence of a large fraction (>90%) of immobile species. We present the background theory, computer simulations, and analysis of measurements on fluorescent microspheres to demonstrate proof of principle, capabilities, and limitations of the method. We demonstrate mapping of flow vectors for mixed samples containing fluorescent microspheres with different emission wavelengths using space time image cross-correlation. We also present results from two-photon laser-scanning microscopy studies of alpha-actinin/enhanced green fluorescent protein fusion constructs at the basal membrane of living CHO cells. Using space-time image correlation spectroscopy (STICS), we are able to measure protein fluxes with magnitudes of mum/min from retracting lamellar regions and protrusions for adherent cells. We also demonstrate the measurement of correlated directed flows (magnitudes of mum/min) and diffusion of interacting alpha5 integrin/enhanced cyan fluorescent protein and alpha-actinin/enhanced yellow fluorescent protein within living CHO cells. The STICS method permits us to generate complete transport maps of proteins within subregions of the basal membrane even if the protein concentration is too high to perform single particle tracking measurements.

Actinin↗
PubMed1999

Multiple generators in the auditory automatic discrimination process in humans.

To reveal the spatiotemporal characteristics of the auditory automatic discrimination process, mismatch negativity (MMN) generators were assessed with a high-resolution EEG system (128ch) and scalp current density (SCD) analysis. Ten normal volunteers participated in the study. Event-related potentials were recorded during a selective attention task. Sequential SCD mappings revealed that a current sink/source combination in the left temporal regions and a current sink in the right frontotemporal regions appeared around 200 msec irrespective of the ear of stimulation. Moreover, a parietal sink/source combination was demonstrated on the right hemisphere around 240 ms irrespective of the ear of stimulation. These findings demonstrate that the auditory automatic change detection process is, both spatially and temporally, a multiple-generated system.

Acoustic Stimulation↗
PubMed2004

Spatial and temporal analysis of the distribution of hantavirus pulmonary syndrome in Buenos Aires Province, and its relation to rodent distribution, agricultural and demographic variables.

We studied the spatial and temporal distribution of Hantavirus Pulmonary Syndrome (HPS) cases from 1998 to 2001 in the Buenos Aires Province, Argentina. HPS is a severe viral disease whose natural reservoir are rodents of the subfamily Sigmodontinae (Muridae) and which occurs in many countries of South and North America. We considered two spatial arrangements: cells of 18.5 x 18.5 km(2); and departments, the political subdivisions of the province, as spatial units. We tested the departure from a Poisson distribution of the number of cases per cell and per month with the Variance/Mean index, while the interaction between spatial and temporal clustering was tested by means of the Knox and Mantel tests. We constructed probability maps in which the HPS rates per department were considered Poisson variates according to population, area and the product of population and area. We analysed the relation between rodent distribution, environmental and demographic variables and HPS cases conducting preliminary univariate analysis from which we selected variables to enter in general linearized models. We found that both the spatial and temporal distribution of cases is strongly aggregated. The spatiotemporal interaction appears to be related to a strong seasonality and the existence of particular ecological conditions rather than epidemic transmission of the disease. The main explanatory variables for the distribution of HPS cases among the departments of the Buenos Aires Province were human population, the distribution of the rodent Oxymycterus rufus and evapotranspiration. The last two variables are probably indicators of favourable ecological conditions for the reservoirs, which encompass other variables not taken into account in this study.

Agriculture↗
PubMed2004

Validation of volume and mass assessments for human fetal heart imaging by 4-dimensional spatiotemporal image correlation echocardiography: in vitro balloon model experiments.

OBJECTIVE: This study was designed to validate a slow-sweep real-time 4-dimensional (4D) spatiotemporal image correlation method for producing quantitatively accurate dynamic fetal heart images using an in vitro pulsatile balloon model and apparatus. METHODS: To model fetal heart chambers, asymmetric double-walled finger stalls (tips of surgical latex gloves) were used and attached to a laboratory-designed circuit that allowed calibrated changes in the inner balloon volume as well as an intermediate gel mass interposed between the 2 layers. The water-submerged model was attached to a small-volume pulsatile pump to produce phasic changes in volume within the inner balloon at a fixed rate. A sonography system with 4D spatiotemporal image correlation (STIC) capabilities was used for 3-dimensional (3D) and 4D data acquisition. Volume data were analyzed by customized radial summation techniques with 4D data analysis software and compared with known volumes and masses. RESULTS: Fifty-six individual volumes ranging from 2.5 to 10 mL were analyzed. Volume and mass measurements with 4D STIC were highly correlated (R2 > 0.90). The mean percentage error was better (<6%) for volumes exceeding 4 mL and was as low as 0.3% for 6-mL estimations. Measurements in the diastolic phase were the most accurate, followed by mass estimations equivalent to chamber walls. There was a wider range of percentage error in the lowest volumes tested (2.5 mL), which might have arisen from difficulties in spatial resolution or distortions from within the model apparatus itself. Resolution limitations of 4D technology in combination with extremely small volume targets may explain higher error rates at these small volumes. CONCLUSIONS: Four-dimensional STIC is an acceptably accurate method for volume and mass estimations in the ranges comparable with mid- and late-gestation fetal hearts. It is particularly accurate for diastolic estimations, for chamber wall mass measurements, and at volumes of greater than 2.5 mL. This study validates use of 4D STIC technology to overcome the limitations of nongated 3D technology for phasic and quantitative assessments in fetal echocardiography.

Echocardiography, Four-Dimensional↗
PubMed2000

Anatomically informed basis functions.

This paper introduces the general framework, concepts, and procedures of anatomically informed basis functions (AIBF), a new method for the analysis of functional magnetic resonance imaging (fMRI) data. In contradistinction to existing voxel-based univariate or multivariate methods the approach described here can incorporate various forms of prior anatomical knowledge to specify sophisticated spatiotemporal models for fMRI time-series. In particular, we focus on anatomical prior knowledge, based on reconstructed gray matter surfaces and assumptions about the location and spatial smoothness of the blood oxygenation level dependent (BOLD) effect. After reconstruction of the grey matter surface from an individual's high-resolution T1-weighted MRI, we specify a set of anatomically informed basis functions, fit the model parameters for a single time point, using a regularized solution, and finally make inferences about the estimated parameters over time. Significant effects, induced by the experimental paradigm, can then be visualized in the native voxel-space or on the reconstructed folded, inflated, or flattened cortical surface. As an example, we apply the approach to a fMRI study (finger opposition task) and compare the results to those of a voxel-based analysis as implemented in the Statistical Parametric Mapping package (SPM99). Additionally, we show, using simulated data, that the approach offers several desirable features particularly in terms of superresolution and localization.

Brain↗
PubMed1997

A goldfish Notch-3 homologue is expressed in neurogenic regions of embryonic, adult, and regenerating brain and retina.

Members of the Notch gene family are thought to be involved in the regulation of cell fate decisions in a variety of embryonic tissues, particularly in the developing central nervous system (CNS) in Drosophila and vertebrates. In goldfish the CNS continues to develop and add neurons well into adulthood and has the capacity to regenerate new neurons. Using probes derived from Xenopus Notch to screen an adult goldfish retinal cDNA library, followed by 5' RACE, we isolated a partial cDNA for a goldfish Notch homologue, G-Notch. Sequence alignment supported assignment of G-Notch to the Notch-3 class. Northern blot analysis revealed a single transcript of > 8 kb, and RNase protection assays indicated that G-Notch is expressed in eye and brain but not muscle of adult goldfish. The spatiotemporal pattern of expression of G-Notch was defined from early embryonic stages to adulthood by in situ hybridization. Expression in the embryonic CNS was localized to neurogenic regions and was downregulated in differentiated cell populations. In adult goldfish, expression persisted in and adjacent to the germinal zones in the retina and the brain. Weak expression was seen in scattered cells in the inner nuclear layer of the retina, which might include neurogenic stem cells. Following retinal lesions (puncture wounds or laser lesions restricted to photoreceptors in the outer nuclear layer), G-Notch was upregulated in proliferating cell populations throughout the retina, in association with a generalized mitogenic response. In the region of the laser lesion, where earlier studies have demonstrated that photoreceptors are regenerating at 1-3 weeks following the lesion, G-Notch expressing cells were abundant in the outer nuclear layer. These observations suggest that retinal regeneration involves the re-expression of an important developmental signaling molecule in neuroepithelial cells resident in the differentiated retina.

Amino Acid Sequence↗
PubMed2005

Multivariate parametric spatiotemporal models for county level breast cancer survival data.

In clustered survival settings where the clusters correspond to geographic regions, biostatisticians are increasingly turning to models with spatially distributed random effects. These models begin with spatially oriented frailty terms, but may also include further region-level terms in the parametrization of the baseline hazards or various covariate effects (as in a spatially-varying coefficients model). In this paper, we propose a multivariate conditionally autoregressive (MCAR) model as a mixing distribution for these random effects, as a way of capturing correlation across both the regions and the elements of the random effect vector for any particular region. We then extend this model to permit analysis of temporal cohort effects, where we use the term "temporal cohort" to mean a group of subjects all of whom were diagnosed with the disease of interest (and thus, entered the study) during the same time period (say, calendar year). We show how our spatiotemporal model may be efficiently fit in a hierarchical Bayesian framework implemented using Markov chain Monte Carlo (MCMC) computational techniques. We illustrate our approach in the context of county-level breast cancer data from 22 annual cohorts of women living in the state of Iowa, as recorded by the Surveillance, Epidemiology, and End Results (SEER) database. Hierarchical model comparison using the Deviance Information Criterion (DIC), as well as maps of the fitted county-level effects, reveal the benefit of our approach.

Adult↗
PubMed2005

Three-dimensional gait biomechanics in Parkinson's disease: evidence for a centrally mediated amplitude regulation disorder.

We examined whether people with Parkinson's disease (PD) have a central amplitude regulation disorder using three-dimensional (3-D) gait analyses to compare the effects of medication and attentional strategies on gait in 12 PD subjects and 12 matched comparison subjects. Subjects with PD first performed several 10-m gait trials at preferred speed while off levodopa. They then walked at preferred speed on levodopa; off levodopa with cues; and on levodopa with cues. Control subjects walked at preferred speed and then with visual cues to match their stride length to PD values. As well as spatiotemporal footstep data, pelvic and lower limb kinematic profiles and angle-angle diagrams were produced for sagittal, coronal, and transverse plane movements using a 3-D motion analysis system. In people with PD, decreased step length was accompanied by reduced movement amplitude across all lower limb joints, in all movement planes. When control subjects were required to walk with short steps matched to the size of PD comparisons, they displayed a similar multijoint reduction in amplitude. For PD subjects, both levodopa and visual cues increased movement amplitude across all lower limb joints. Amplitude increased further when levodopa and visual cues were combined, resulting in normalization of step length. This finding suggested that reduced step length is due to a mismatch between cortically selected movement amplitude and basal ganglia maintenance mechanisms. Levodopa and cues normalized amplitude across all joints by altering motor set and bypassing defective basal ganglia mechanisms.

Aged↗
PubMed2002

Top-down influence in early visual processing: a Bayesian perspective.

Traditional views of visual processing suggest that early visual neurons are static spatiotemporal filters that extract local features by feedforward computation. The extracted information is then fed forward through a chain of modules to successively higher visual areas for further analysis. Recording from early visual neurons in awake behaving monkeys, we revealed there are many levels of complexity in the information processing of the early visual cortex. We found that the early visual neurons not only are sensitive to features within their receptive fields (RFs) but also to the global context of a visual scene, the behavioral relevance of the stimuli and the experience of the animals. These findings suggest that the early visual cortex (V1 and V2) is tightly coupled to and highly interactive with the rest of the visual system. The top-down interaction, mediated by recurrent feedback connections, introduces contextual information to influence the perceptual inference in the early visual cortex.

Algorithms↗
PubMed2001

Levels of word processing and incidental memory: dissociable mechanisms in the temporal lobe.

Word recall is facilitated when deep (e.g. semantic) processing is applied during encoding. This fact raises the question of the existence of specific brain mechanisms supporting different levels of information processing that can modulate incidental memory performance. In this study we obtained spatiotemporal brain activation profiles, using magnetic source imaging, from 10 adult volunteers as they performed a shallow (phonological) processing task and a deep (semantic) processing task. When phonological analysis of the word stimuli into their constituent phonemes was required, activation was largely restricted to the posterior portion of the left superior temporal gyrus (area 22). Conversely, when access to lexical/semantic representations was required, activation was found predominantly in the left middle temporal gyrus and medial temporal cortex. The differential engagement of each mechanism during word encoding was associated with dramatic changes in subsequent incidental memory performance.

Acoustic Stimulation↗
PubMed2005

Analysis of single-unit responses to emotional scenes in human ventromedial prefrontal cortex.

Lesion and functional imaging studies in humans have shown that the ventral and medial prefrontal cortex is critically involved in the processing of emotional stimuli, but both of these methods have limited spatiotemporal resolution. Conversely, neurophysiological studies of emotion in nonhuman primates typically rely on stimuli that do not require elaborate cognitive processing. To begin bridging this gap, we recorded from a total of 267 neurons in the left and right orbital and anterior cingulate cortices of four patients who had chronically implanted depth electrodes for monitoring epilepsy. Peristimulus activity was recorded to standardized, complex visual scenes depicting neutral, pleasant, or aversive content. Recording locations were verified with postoperative magnetic resonance imaging. Using a conservative, multistep statistical evaluation, we found significant responses in 56 neurons; 16 of these were selective for only one emotion class, most often aversive. The findings suggest sparse and widely distributed processing of emotional value in the prefrontal cortex, with a predominance of responses to aversive stimuli.

Action Potentials↗
PubMed2002

Effects of temporal modelling on the statistical uncertainty of spatiotemporal distributions estimated directly from dynamic SPECT projections.

Artefacts can result when reconstructing a dynamic image sequence from inconsistent single photon emission computed tomography (SPECT) projection data acquired by a slowly rotating gantry. The artefacts can lead to biases in kinetic parameters estimated from time-activity curves generated by overlaying volumes of interest on the images. Insufficient sampling and truncation of projections by cone-beam collimators can cause additional artefacts. To overcome these sources of bias in conventional image based dynamic data analysis, we have been investigating the estimation of time-activity curves and kinetic model parameters directly from dynamic SPECT projection data by modelling the spatial and temporal distribution of the radiopharmaceutical throughout the projected field of view. In the present work, we perform Monte Carlo simulations to study the effects of the temporal modelling on the statistical variability of the reconstructed spatiotemporal distributions. The simulations utilize fast methods for fully four-dimensional (4D) direct estimation of spatiotemporal distributions and their statistical uncertainties, using a spatial segmentation and temporal B-splines. The simulation results suggest that there is benefit in modelling higher orders of temporal spline continuity. In addition, the accuracy of the time modelling can be increased substantially without unduly increasing the statistical uncertainty, by using relatively fine initial time sampling to capture rapidly changing activity distributions.

Algorithms↗
PubMed2001

Transcriptional and spatiotemporal regulation of prolactin receptor mRNA and cooperativity with progesterone receptor function during ductal branch growth in the mammary gland.

Ductal branching within the mammary gland is stimulated by prolactin (PRL) and progesterone (P) acting through their receptors (PRLR and PR). Analysis of mammary gland PRLR expression revealed increasing expression of the long form (L-PRLR) and two of the three short forms (S1- and S3-PRLR) during puberty that became maximal late in pubescence and early gestation, then declined during gestation. By contrast, S2-PRLR mRNA levels remained constant. Examination of stromal PRLR revealed the consistent expression of L-PRLR mRNA. By contrast, S1-PRLR was present only in the mammary fat pad of neonates, whereas high neonatal expression of S2-PRLR became undetectable during puberty. Stromal expression of S3-PRLR decreased to low levels during puberty and was undetectable during lactation and involution. Exogenous PRL stimulated DNA synthesis in both epithelial and adjacent stromal cells in vivo. Distribution of PRLR mRNA in mammary epithelium was homogeneous before puberty and heterogeneous during puberty, gestation, and early lactation. A mutual role for PRLR and PR was suggested wherein PR mRNA increased beyond 6 weeks to maximal levels during puberty and gestation then became undetectable during lactation. In situ hybridization revealed that PR mRNA distribution is homogeneous in the ductal epithelium before 6 weeks and heterogenous during puberty and gestation and that PRLR and PR are similarly distributed in the ductal epithelium. Neither hormone stimulated DNA synthesis in mammary glands of ovariectomized females while their effects interacted markedly. These results demonstrate differential PRLR transcription by epithelial and stromal cells and a similar distribution of PRLR and PR that may facilitate the interaction between P and PRL during ductal branching in the mammary gland.

Adipose Tissue↗