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PubMed2002

Gene expression of the POU factor Brn-3a is regulated by two different promoters.

Expression of the POU transcription factor Brn-3a is regulated spatially and temporally during embryogenesis and can be detected in a particular subset of neurons and neuronal tumors. In the present study, we investigated the transcriptional regulation of Brn-3a expression. The human promoter is TATA-less and contains two bona fide mRNA start sites spread over 500 nucleotides 5' of the ATG translation initiation codon. Furthermore, a second TATA-less promoter was detected in the first intron of the Brn-3a gene and our data suggest that this promoter regulates expression of the shorter isoform of the Brn-3a gene. Transcriptional activity from this promoter was found in neuronal cell lines but not in epithelial cells. The activity of this promoter was strongly enhanced upon deletion of a 24 base pair (bp) DNA element downstream of the transcription initiation sites. In addition, this DNA element was able to repress transcription from a heterologous promoter suggesting a function as a transcriptional silencer. The more distal upstream Brn-3a promoter directing the expression of the longer Brn-3a isoform is not affected by the presence of this putative 24 bp DNA element. We propose therefore that the existence of two promoters in the Brn-3a gene offers a possibility for the observed differential and cell type-specific expression of the gene.

Base Sequence↗
PubMed2006

High-resolution magnetic resonance imaging sinc-interpolation-based subvoxel registration and semi-automated quantitative lateral ventricular morphology employing threshold computation and binary image creation in the study of fatty acid interventions in schizophrenia, depression, chronic fatigue syndrome and Huntington's disease.

Serial high-resolution structural magnetic resonance imaging scans of the brain can now be precisely aligned, with six degrees of freedom (three mutually orthogonal translational and three rotational degrees of freedom around three mutually orthogonal axes), using a rigid-body subvoxel registration technique. This is driven by the in-plane point spread function for images acquired in the Fourier domain with data obtained over a bounded region of k-space, namely the sinc interpolation function, where sinc z = (sin z)/z, with z being any complex number (including zero). Computational subtraction of the three-dimensional Cartesian spatial representation matrices of serially acquired scan data allows for the determination of structural cerebral changes with great precision, since voxel signals from unchanged structures are almost completely cancelled. Thus changes readily show up against a background of noise. Furthermore, lateral ventricular changes can now be accurately quantified using a semi-automated method involving contour production, threshold computation, binary image creation and ventricular extraction. These techniques have been applied to the investigation of the effects on cerebral structure of intervention with fatty acids, particularly the long-chain polyunsaturated n-3 fatty acid eicosapentaenoic acid (EPA), in disorders such as schizophrenia, treatment-resistant depression, chronic fatigue syndrome (myalgic encephalomyelitis or ME), and Huntington's disease.

Atrophy↗
PubMedDate not supplied

Characterization of the point spread function and modulation transfer function of scattered radiation using a digital imaging system.

A digital radiographic system was used to measure the distribution of scattered x radiation from uniform slabs of Lucite at various thicknesses. Using collimation and air gap techniques, [primary + scatter] images and primary images were digitally acquired, and subtracted to obtain scatter images. The scatter distributions measured using small circular apertures were computer fit to an analytical function, representing the circular aperture function convolved with a modified Gaussian point spread function (PSF). On the basis of goodness of fit criterion, the proposed Gaussian function is a very good model for the scatter PSF. The measured scatter PSF's are reported for various Lucite thicknesses. Using the PSF's, the modulation transfer functions are calculated, and this spatial frequency information may have value in analytical scatter removal techniques, grid design, and air gap optimization.

Computers↗
PubMed1991

The spatial and temporal distribution of polarizing activity in the flank of the pre-limb-bud stages in the chick embryo.

The presence of polarizing activity in the limb buds of developing avian embryos determines the pattern of the anteroposterior axis of the limbs in the adult. Maps of the spatial distribution and the strength of the signal within limb buds of different stages are well documented. Polarizing activity can also be found in Hensen's node in the early embryo. We have mapped the distribution of polarizing activity as it emerges from Hensen's node and spreads into the flank tissue of the embryo. There is a clear change in the local pattern of expression of polarizing activity between stage 8 and 18. Almost no activity is measured for stages 8 and 9. More or less uniform levels of around 10% are spread along the flank lateral to the unsegmented somitic mesoderm from somite position 12 to 22 in stage 10 embryos. Some 6 to 8 h later at stage 12, there is a distinct peak of activity at somite position 18, the middle of the wing field. This peak increases at stages 13 to 15 and its position traverses to the posterior edge of the wing field. Full strength of activity is reached shortly before the onset of limb bud formation at stage 16 to 17. Stages 16 to 18 were investigated for polarizing activity in the wing and the leg field. Low levels of polarizing activity are present in the anterior leg field at stages 16 and 17 but have disappeared by stage 18 and all activity is confined to the posterior part of the leg bud.

Animals↗
PubMed2006

Scattering of light from quasi-homogeneous sources by quasi-homogeneous media.

The field generated by scattering of light from a quasi-homogeneous source on a quasi-homogeneous, random medium is investigated. It is found that, within the accuracy of the first-order Born approximation, the far field satisfies two reciprocity relations (sometimes called uncertainty relations). One of them implies that the spectral density (or spectral intensity) is proportional to the convolution of the spectral density of the source and the spatial Fourier transform of the correlation coefficient of the scattering potential. The other implies that the spectral degree of coherence of the far field is proportional to the convolution of the correlation coefficient of the source and the spatial Fourier transform of the strength of the scattering potential. While the case we consider might seem restrictive, it is actually quite general. For instance, the quasi-homogeneous source model can be used to describe the generation of beams with different coherence properties and different angular spreads. In addition, the quasi-homogeneous scattering model adequately describes a wide class of turbulent media, including a stratified, turbulent atmosphere and confined plasmas.

Journal Article↗
PubMed1998

[Comparison of atrial premature depolarization topography during vagal stimulation and humoral acetylcholine administration].

Epicardial atrial mapping in open-chest dogs during different cholinergic influences has shown that, in acetylcholine administration and vagal stimulation, spatial distribution of atrial premature depolarisation (APDs) seems to be similar to prevalence of ectopic sources from both atria and atrial septum. Spatial distribution of the APDs in acetylcholine administration in the sinus node artery was limited to the region of this artery so that the APDs mainly arise from intercaval area of the right atrium and from atrial septum, but never from the left atrium. The latent pacemakers spread over both atria and atrial septum, could participate in initiation of cholinergically-induced APDs and atrial fibrillation. A direct effect of acetylcholine seems to be necessary for development of arrhythmic activity of the latent pacemakers.

Acetylcholine↗
PubMed1982

Spatial properties of nociceptor sensitization following heat injury of the skin.

A brief noxious heat stimulus applied to half of the receptive field of each cutaneous nociceptor resulted in most cases in the enhanced responsiveness of that half to subsequent heat stimuli (sensitization). No change in responsiveness to heat was observed in the other half of the receptive field, indicating that the effects of heat sensitization did not spread from the site of injury. In certain instances, the receptive field area increased, but the enlargement occurred only within the area of injury. The latter suggests the existence of outlying terminal endings of the parent axon that are normally unresponsive to non-injurious mechanical or heat stimuli but become responsive to these stimuli following injury.

Action Potentials↗
PubMed2003

A penalized-likelihood image reconstruction method for emission tomography, compared to postsmoothed maximum-likelihood with matched spatial resolution.

Regularization is desirable for image reconstruction in emission tomography. A powerful regularization method is the penalized-likelihood (PL) reconstruction algorithm (or equivalently, maximum a posteriori reconstruction), where the sum of the likelihood and a noise suppressing penalty term (or Bayesian prior) is optimized. Usually, this approach yields position-dependent resolution and bias. However, for some applications in emission tomography, a shift-invariant point spread function would be advantageous. Recently, a new method has been proposed, in which the penalty term is tuned in every pixel to impose a uniform local impulse response. In this paper, an alternative way to tune the penalty term is presented. We performed positron emission tomography and single photon emission computed tomography simulations to compare the performance of the new method to that of the postsmoothed maximum-likelihood (ML) approach, using the impulse response of the former method as the postsmoothing filter for the latter. For this experiment, the noise properties of the PL algorithm were not superior to those of postsmoothed ML reconstruction.

Algorithms↗
PubMed2005

Simultaneous beam geometry and intensity map optimization in intensity-modulated radiation therapy.

PURPOSE: In current intensity-modulated radiation therapy (IMRT) plan optimization, the focus is on either finding optimal beam angles (or other beam delivery parameters such as field segments, couch angles, gantry angles) or optimal beam intensities. In this article we offer a mixed integer programming (MIP) approach for simultaneously determining an optimal intensity map and optimal beam angles for IMRT delivery. Using this approach, we pursue an experimental study designed to (a) gauge differences in plan quality metrics with respect to different tumor sites and different MIP treatment planning models, and (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around the planning target volume (PTV)--and its use for designing conformal plans. METHODS AND MATERIALS: Our treatment planning models use two classes of decision variables to capture the beam configuration and intensities simultaneously. Binary (0/1) variables are used to capture "on" or "off" or "yes" or "no" decisions for each field, and nonnegative continuous variables are used to represent intensities of beamlets. Binary and continuous variables are also used for each voxel to capture dose level and dose deviation from target bounds. Treatment planning models were designed to explicitly incorporate the following planning constraints: (a) upper/lower/mean dose-based constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within this constrained solution space, five optimization strategies involving clinical objectives were analyzed: optimize total intensity to PTV, optimize total intensity and then optimize conformity, optimize total intensity and then optimize homogeneity, minimize total dose to critical structures, minimize total dose to critical structures and optimize conformity simultaneously. We emphasize that the objectives that include optimizing conformity make use of the critical-normal-tissue-ring. Three tumor sites: head-and-neck, pediatric brain, and prostate are used for comparison. RESULTS: The critical-normal-tissue-ring acts as a good device for enforcing conformity. Trends in the characteristics and quality of plans resulting from each model were observed. Attempts to reduce dose to critical structures tend to worsen PTV conformity (1.542 to 3.092) and homogeneity (1.223 to 1.984), depending on the relative size and spatial distance of the critical structures to the PTV. When the critical structures are relatively small compared with the PTV (as in the case for the pediatric brain tumor, where each is less than 15% in volume), dose reduction to critical structures is accompanied by much worse scores in conformity (2.482) and homogeneity (1.984). When the critical structures are larger, as in the case of head-and-neck (approximately 50%), the conformity and homogeneity deterioration is less significant (1.542 and 1.239, respectively). There is a clear tradeoff between homogeneity, conformity, and minimum dose to organs at risk (OARs). For head-and-neck and pediatric brain tumor, the model that minimizes total dose to critical structures and optimizes conformity simultaneously offers a compromise among these factors, resulting in reduced critical structure dose with conformal and homogeneous plans. In the prostate case, the tumor is smaller than the two large nearby critical structures, and all models provide very homogeneous PTV dose distribution. However, minimizing dose to critical structures worsens conformity, as it spreads the radiation to the area surrounding the PTV. The maximum dose to the critical structures also increases slightly. Compared with plans used in the clinic which generally have uniformly spaced beam angles, the optimal clinically acceptable plans obtained via the methods herein do not have equispaced beams. The optimal beam angles returned appear to be nonintuitive, and depend on PTV size and geometry and the spatial relationship between the tumor and critical structures. CONCLUSIONS: The MIP model described allows simultaneous optimization over the space of beamlet fluence weights and beam and couch angles. Based on experiments with tumor data, this approach can return good plans that are clinically acceptable and practical. This work distinguishes itself from recent IMRT research in several ways. First, in previous methods beam angles are selected before intensity map optimization. Herein, we employ 0/1 variables to model the set of candidate beams, and thereby allow the optimization process itself to select optimal beams. Second, instead of incorporating dose-volume criteria within the objective function as in previous work, herein, a combination of discrete and continuous variables associated with each voxel provides a mechanism to strictly enforce dose-volume criteria within the constraints. Third, using the construct of critical-normal-tissue-ring within the objective function can enhance the achievement of conformal plans. Based on the three tumor sites considered, it appears that volume and spatial geometry with respect to the PTV are important factors to consider when selecting objectives to optimize, and in estimating how well suited a particular model is for achieving a specified goal.

Algorithms↗
PubMed1999

Concentrations of human cardiac phosphorus metabolites determined by SLOOP 31P NMR spectroscopy.

Human cardiac 31P nuclear magnetic resonance (NMR) spectra are usually quantified in relative terms, i.e., the ratio of metabolite signals is calculated. If 31P NMR spectroscopy of the heart is to emerge as a clinically relevant diagnostic modality, reliable quantification of absolute concentrations of 31P metabolites is required. We applied spectral localization with optimal point spread function (SLOOP) 31P NMR spectroscopy to measure absolute concentrations of phosphocreatine (PCr) and adenosine triphosphate (ATP) in human myocardium. The accuracy of the quantification was first validated in a phantom study. Seven healthy volunteers (aged 19-29 years) were then examined at 1.5 T using a nominal spatial resolution of 25 mL. SLOOP allowed us to obtain localized spectra from compartments anatomically matched to the left ventricular wall. The a priori knowledge of the anatomical structure was obtained from 1H images. The spatially varying effects of saturation, off-resonance, and sensitivity were considered during the reconstruction process. Metabolites were quantified with reference to an external 31P standard. Concentrations of 9.0 +/- 1.2 and 5.3 +/- 1.2 mmol/kg wet wt (mean +/- SD, n = 9) were determined for PCr and ATP in normal heart, respectively. The influence of nuclear Overhauser enhancement on metabolite quantification is discussed.

Adenosine Triphosphate↗
PubMed2004

Multicellular computer simulation of morphogenesis: blastocoel roof thinning and matrix assembly in Xenopus laevis.

In the blastocoel roof (BCR) of the Xenopus laevis embryo, epibolic movements are driven by the radial intercalation of deep cell layers and the coordinate spreading of the overlying superficial cell layer. Thinning of the lateral margins of the BCR by radial intercalation requires fibronectin (FN), which is produced and assembled into fibrils by the inner deep cell layer of the BCR. A cellular automata (CA) computer model was developed to analyze the spatial and temporal movements of BCR cells during epiboly. Simulation parameters were defined based on published data and independent results detailing initial tissue geometry, cell numbers, cell intercalation rates, and migration rates. Hypotheses regarding differential cell adhesion and FN assembly were also considered in setting system parameters. A 2-dimensional model simulation was developed that predicts BCR thinning time of 4.8 h, which closely approximates the time required for the completion of gastrulation in vivo. Additionally, the model predicts a temporal increase in FN matrix assembly that parallels fibrillogenesis in the embryo. The model is capable of independent predictions of cell rearrangements during epiboly, and here was used to predict successfully the lateral dispersion of a patch of cells implanted in the BCR, and increased assembly of FN matrix following inhibition of radial intercalation by N-cadherin over-expression.

Animals↗
PubMed2001

Spatial and stochastic simulation to compare two emergency-vaccination strategies with a marker vaccine in the 1997/1998 Dutch Classical Swine Fever epidemic.

Two alternative emergency-vaccination strategies with a marker vaccine that could have been applied in the 1997/1998 Dutch Classical Swine Fever (CSF) epidemic were evaluated in a modified spatial, temporal and stochastic simulation model: InterCSF. In strategy 1, vaccination would be applied only to overcome a shortage in destruction capacities. Destruction of all pigs on vaccinated farms distinguishes this strategy from strategy 2, which assumes intra-Community trade of vaccinated pig meat. InterCSF simulates the spread of CSF between farms through local spread and three contact types. Disease spread is affected by control measures implemented through different mechanisms. Economic results were generated by a separate model that calculated the direct costs (including the vaccination costs) and consequential losses for farmers and related industries subjected to control measures. The comparison (using epidemiological and economic results) between the different emergency-vaccination strategies with an earlier simulated preventive-slaughter scenario led to some general conclusions on the Dutch CSF epidemic. Both emergency-vaccination strategies were hardly more efficient than the non-vaccination scenario. The intra-Community trade strategy (vaccination-strategy 2) was the least costly of all three scenarios.

Animals↗
PubMed1998

The evolution of interspecific mutualisms.

Interspecific mutualisms are widespread, but how they evolve is not clear. The Iterated Prisoner's Dilemma is the main theoretical tool to study cooperation, but this model ignores ecological differences between partners and assumes that amounts exchanged cannot themselves evolve. A more realistic model incorporating these features shows that strategies that succeed with fixed exchanges (e. g., Tit-for-Tat) cannot explain mutualism when exchanges vary because the amount exchanged evolves to 0. For mutualism to evolve, increased investments in a partner must yield increased returns, and spatial structure in competitive interactions is required. Under these biologically plausible assumptions, mutualism evolves with surprising ease. This suggests that, contrary to the basic premise of past theoretical analyses, overcoming a potential host's initial defenses may be a bigger obstacle for mutualism than the subsequent recurrence and spread of noncooperative mutants.

Biological Evolution↗
PubMed1990

Expression of the neuronal surface glycoprotein Thy-1 is under post-transcriptional control, and is spatially regulated, in the developing olfactory system.

Expression of the neuronal cell surface glycoprotein Thy-1 has been studied during the development of the olfactory bulb in mice and rats, using in situ hybridisation and immunohistochemistry to follow the appearance of Thy-1 mRNA and protein, respectively. The mRNA was first detected 4 days before birth on all mitral cells, the main projection neuron of the bulb, as they formed a distinct layer and grew dendrites. At no stage was any spatial gradient of expression of Thy-1 mRNA evident around the mitral cell layer. Thy-1 protein, on the other hand, was first detectable 2 days later on a group of mitral cells immediately adjacent the point of entry of the olfactory nerve. The numbers of immunoreactive cells spread, over the next 7 days, to include all mitral cells, those located rostrally and laterally in the bulb being slowest to express Thy-1 protein. Thus there was a spatiotemporal gradient of expression of Thy-1 protein, which was not apparent in the earlier general expression of its mRNA, suggesting that some further inductive signal was required after transcription in order to get effective production of protein. Analysis of the growth of the mitral cell axons in the lateral olfactory tract suggested this signal was related to the cessation of axonogenesis, as Thy-1 immunoreactivity became detectable on these axons only when their expression of the transient epitope detected by the G10 antibody, present on microtubule-associated protein (MAP)1x only during axonal growth, declined. For the first week after Thy-1 protein appeared on mitral cells, it was not distributed uniformally on their surface. Immunoreaction was relatively weak on the somatic surface, and the molecule appeared to be entirely excluded from the distal regions of its main dendrite, above the outer plexiform layer. Here the dendrite reaches up to the synaptic glomeruli formed with the incoming olfactory nerve axons. These distal regions of the dendritic shaft became immunoreactive only after the periglomerular cells had first begun to express Thy-1 protein in the glomeruli. Immunolabelling of the somatic membrane then increased, to give the adult pattern of uniform Thy-1 labelling of the neuronal membrane by the end of the second postnatal week. It is suggested that some of the molecular features of Thy-1, and anatomical features of the main bulb, could interact to produce this initial restriction of Thy-1 to particular parts of the mitral cell surface.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2003

Comparison of linear and rotationally shearing interferometric layouts for extrasolar planet detection from space.

We use the point spread function and the modulation transfer function (MTF) as two figures-of-merit to evaluate the performance of the multiaperture interferometric configurations for the detection of a faint planet in the vicinity of its bright star. We design nonredundant interferometric layouts that provide satisfactory coverage of the spatial frequencies of interest. We propose a design incorporating a rotating, rotationally shearing interferometer in a gravity-free environment and compare its performance with the Earth-based, fixed, linear configurations. The side peak of its MTF may be centered on the coordinate associated with a likely planet spatial frequency, resulting in planet signal enhancement and isolation.

Journal Article↗
PubMed2006

Dynamic distribution of Thr3-phosphorylated histone H3 in CHO cells in mitosis.

The phosphorylation of histone H3 at Ser10, Ser28, Thr11 and Thr3 of the amino terminal has been proved related to mitosis of the mammalian cells. However, the function of the Thr3 phosphorylation of H3 remains unclear. In this study, indirect immunofluorescence labelling and laser confocal microscopy were used to examine the cellular dynamic distribution of Thr3-phosphorylated H3 at mitosis in CHO cells. The results showed that the Thr3 phosphorylation began at early prophase and spread throughout the chromosomes at late prophase. At metaphase, most of the Thr3-phosphorylated H3 was distributed along the entire chromosomal arms and maintained until early anaphase. During late anaphase and telophase, the fluorescent signal of Thr3-phosphorylated H3 disappeared from chromosomes. There was a precise spatial and temporal correlation between H3 phosphorylation of Thr3 and stages of chromatin condensation. The timing of Thr3 phosphorylation and dephosphorylation in mitosis were similar to that reported for Thr11 phosphorylation of H3. The Thr3-phosphorylated H3 localized along the arms of chromosomes during metaphase and early anaphase. It was different from the Ser10-phosphorylated H3, which localized at telomere regions, and Thr11-phosphorylated H3, which localized at centromeres. The results suggest that the Thr3 phosphorylation of histone H3 may play a specific role, which is different from Ser10 phosphorylation and Thr11 phosphorylation in mitosis.

Animals↗
PubMed1994

Spatial and temporal signalling by calcium.

Recent research has shown the importance of the spatial and temporal aspects of calcium signals, which depend upon regenerative properties of the inositol trisphosphate and ryanodine receptors that regulate the release of calcium from internal stores. Initiation sites have been found to spontaneously release calcium, recognized as 'hot spots' or 'sparks', and can trigger a wave that spreads through a process of calcium-induced calcium release.

Animals↗
PubMed2005

Spatial epidemiology of the Asian honey bee mite (Varroa destructor) in the North Island of New Zealand.

We describe the spatial epidemiology of Varroa destructor infestation among honey bee apiaries in the greater Auckland area of the North Island of New Zealand. The study population was comprised of 641 apiaries located within the boundaries of the study area on 11 April 2000. Cases were those members of the study population declared Varroa-infested on the basis of testing conducted between April and June 2000. The odds of Varroa was highest in apiaries in the area surrounding transport and storage facilities in the vicinity of Auckland International Airport. A mixed-effects geostatistical model, accounting for spatial extra-binomial variation in Varroa prevalence, showed a 17% reduction in the odds of an apiary being Varroa infested for each kilometre increase in the squared distance from the likely site of incursion (95% Bayesian credible interval 7-28%). The pattern of spatially autocorrelated risk that remained after controlling for the effect of distance from the likely incursion site identified areas thought to be 'secondary' foci of Varroa infestation initiated by beekeeper-assisted movement of infested bees. Targeted investigations within these identified areas indicated that the maximum rate of local spread of Varroa was in the order of 12 km/year (interquartile range 10-15 km/year).

Animals↗