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At least 1,765 records · Page 98Linked to original sources
PubMed2006

Analysis of binding at a single spatially localized cluster of binding sites by fluorescence recovery after photobleaching.

Cells contain many subcellular structures in which specialized proteins locally cluster. Binding interactions within such clusters may be analyzed in live cells using models for fluorescence recovery after photobleaching (FRAP). Here we analyze a three-dimensional FRAP model that accounts for a single spatially localized cluster of binding sites in the presence of both diffusion and impermeable boundaries. We demonstrate that models completely ignoring the spatial localization of binding yield poor estimates for the binding parameters within the binding site cluster. In contrast, we find that ignoring only the restricted axial height of the binding-site cluster is far less detrimental, thereby enabling the use of computationally less expensive models. We also identify simplified solutions to the FRAP model for limiting behaviors where either diffusion or binding dominate. We show how ignoring a role for diffusion can sometimes produce serious errors in binding parameter estimation. We illustrate application of the method by analyzing binding of a transcription factor, the glucocorticoid receptor, to a tandem array of mouse mammary tumor virus promoter sites in live cells, obtaining an estimate for an in vivo binding constant (10(-7) M), and a first approximation of an upper bound on the transcription-factor residence time at the promoter (approximately 170 ms). These FRAP analysis tools will be important for measuring key cellular binding parameters necessary for a complete and accurate description of the networks that regulate cellular behavior.

Adenocarcinoma↗
PubMed1994

Algorithms for automated characterization of cell populations in thick specimens from 3-D confocal fluorescence microscopy data.

Methods are presented for the automated, quantitative and three-dimensional (3-D) analysis of cell populations in thick, essentially intact tissue sections while maintaining intercell spatial relationships. This analysis replaces current manual methods which are tedious and subjective. The thick sample is imaged in three dimensions using a confocal scanning laser microscope. The stack of optical slices is processed by a 3-D segmentation algorithm that separates touching and overlapping structures using localization constraints. Adaptive data reduction is used to achieve computational efficiency. A hierarchical cluster analysis algorithm is used automatically to characterize the cell population by a variety of cell features. It allows automatic detection and characterization of patterns such as the 3-D spatial clustering of cells, and the relative distributions of cells of various sizes. It also permits the detection of structures that are much smaller, larger, brighter, darker, or differently shaped than the rest of the population. The overall method is demonstrated for a set of rat brain tissue sections that were labelled for tyrosine hydroxylase using fluorescein-conjugated antibodies. The automated system was verified by comparison with computer-assisted manual counts from the same image fields.

Algorithms↗
PubMed2006

Mechanistic home range models capture spatial patterns and dynamics of coyote territories in Yellowstone.

Patterns of space-use by individuals are fundamental to the ecology of animal populations influencing their social organization, mating systems, demography and the spatial distribution of prey and competitors. To date, the principal method used to analyse the underlying determinants of animal home range patterns has been resource selection analysis (RSA), a spatially implicit approach that examines the relative frequencies of animal relocations in relation to landscape attributes. In this analysis, we adopt an alternative approach, using a series of mechanistic home range models to analyse observed patterns of territorial space-use by coyote packs in the heterogeneous landscape of Yellowstone National Park. Unlike RSAs, mechanistic home range models are derived from underlying correlated random walk models of individual movement behaviour, and yield spatially explicit predictions for patterns of space-use by individuals. As we show here, mechanistic home range models can be used to determine the underlying determinants of animal home range patterns, incorporating both movement responses to underlying landscape heterogeneities and the effects of behavioural interactions between individuals. Our analysis indicates that the spatial arrangement of coyote territories in Yellowstone is determined by the spatial distribution of prey resources and an avoidance response to the presence of neighbouring packs. We then show how the fitted mechanistic home range model can be used to correctly predict observed shifts in the patterns of coyote space-use in response to perturbation.

Animals↗
PubMed2004

The role of stimulus ambiguity and movement in spatial navigation: a multiple memory systems analysis of location discrimination.

This paper reviews recent findings about how rats navigate by learning to discriminate among locations. The assumption underlying the experiments and their interpretation is that the information required to do this is learned by three independent, parallel memory systems. One system processes cognitive information (or "knowledge"), a second system processes reinforced stimulus-response associations and a third processes Pavlovian conditioned responses in the form of stimulus-affect associations. The information stored in each system produces behavior that, in some cases, results in a location discrimination. The present experiments focus on three factors that influence what each system learns and whether the resulting memory produces behavior that results in a location discrimination. One factor is whether the locations to be discriminated can be identified by unique, unambiguous stimuli or whether they are ambiguously associated with the same stimuli. The second factor is whether the stimuli are observed passively or whether the rats move among them, voluntarily or involuntarily. The third factor is whether or not the rats perform specific reinforced responses in the presence of the stimuli. Instances of co-operative behavioral outputs from memory systems that facilitate location discriminations and of competitive outputs that impede discriminations are described.

Animals↗
PubMed1996

Detailed behavioral analysis of water maze acquisition under systemic NMDA or muscarinic antagonism: nonspatial pretraining eliminates spatial learning deficits.

A detailed behavioral analysis of water-maze acquisition showed that the N-methyl-D-aspartate (NMDA) antagonist NPC17742 and the muscarinic antagonist scopolamine caused sensorimotor disturbances in behaviors required for maze performances and that these correlated with acquisition impairments in both hidden and visible platform versions of the maze in male rats. Behavioral disturbances included thigmotaxic swimming, swimming over and deflecting off the platform, abnormal swim behavior, and hyperactivity. Rats familiar with the behavioral strategies involved in the task performed normally under NPC17742 or scopolamine. The results indicated that drug-induced sensorimotor disturbances contributed to poor acquisition scores in naive rats. NMDA or muscarinic activity may contribute to but do not appear to be essential for spatial learning in the water maze.

Amino Acids↗
PubMed1996

A digital model of trabecular bone.

A 3D microCT dataset of bovine bone was used to create a digital 3D model simulating trabecular bone. The model serves a dual purpose: It allows for standard quantitative histomorphometric analysis and it approximates the reality e.g. of high resolution CT in vivo datasets of trabecular bone. Thus the model can potentially be used as a reference to develop 2D and 3D structural analysis algorithms applicable in vivo while it simultaneously allows verification of the results of these algorithms by standard histomorphometry. The model can be used as a standard to evaluate the impact of image processing techniques and of restrictions of imaging systems on the quantitative analysis of structural parameters describing a trabecular network. The model can be used for a comparison of 2D and 3D structural analysis methods and for an analysis of decreasing spatial resolution. The effects of segmentation and filtration can be studied separately and grayscale analysis is possible. As examples standard 2D histomorphometry and the analysis of topological parameters like node number and trabecular network length were applied to the model. The influence of spatial resolution was investigated by decreasing the spatial resolution of the digital model. The bone surface area determined by 3D surface triangulation was only 4% smaller than the surface area determined from the traditional 2D bone histomorphometric parameter bone surface/tissue volume (BS/TV) when 2D results were averaged over all slices of the 3D volume. However, BS/TV showed large (10%) variations among slices within the volume. Both histomorphometric and topological parameters were heavily influenced by spatial resolution and image segmentation. Our initial experience with the digital model indicates a need to investigate bone microstructure based on volume data or to average the 2D results of many slices.

Algorithms↗
PubMed2004

Fourier and wavelet analyses of dental radiographs detect trabecular changes in osteoporosis.

OBJECTIVES: Osteoporosis results in loss of bone mass and microarchitectural deterioration. Dental radiographs potentially offer a means of screening for osteoporosis as they are commonly made on adults. Spatial frequency analyses are well suited to detect subtle changes in image patterns. We hypothesize that individuals with osteoporosis exhibit an altered radiographic trabecular pattern that can be detected by spatial frequency and strut analysis. STUDY DESIGN: Maxillary and mandibular periapical radiographs of 26 women with osteoporosis and 23 controls were examined using one-dimensional discrete Fourier and wavelet analyses in both jaws to measure the spatial frequency distributions of trabecular structures. A strut analysis was also performed. RESULTS: Individuals with osteoporosis revealed an altered trabecular pattern compared to controls. Using Fourier and strut variables allows classification of subjects with 92% sensitivity, 96% specificity, and a 22% cross-validation error rate. Wavelet analysis was also useful but did not perform better than Fourier analysis for subject classification. CONCLUSIONS: Spatial frequency analysis of digitized dental radiographs, especially Fourier analysis, and strut analysis provide value for identifying individuals with osteoporosis.

Case-Control Studies↗
PubMed2003

Spatially-explicit matrix models. A mathematical analysis of stage-structured integrodifference equations.

This paper is concerned with mathematical analysis of the 'critical domain-size' problem for structured populations. Space is introduced explicitly into matrix models for stage-structured populations. Movement of individuals is described by means of a dispersal kernel. The mathematical analysis investigates conditions for existence, stability and uniqueness of equilibrium solutions as well as some bifurcation behaviors. These mathematical results are linked to species persistence or extinction in connected habitats of different sizes or fragmented habitats; hence the framework is given for application of such models to ecology. Several approximations which reduce the complexity of integrodifference equations are given. A simple example is worked out to illustrate the analytical results and to compare the behavior of the integrodifference model to that of the approximations.

Algorithms↗
PubMed1999

Duct changes and K-ras mutations in the disease-free pancreas: analysis of type, age relation and spatial distribution.

Recent molecular studies have suggested that hyperplastic duct lesions of the pancreas are potential precursors of pancreatic ductal carcinoma. This study examines the type, distribution, age-related incidence and K-ras codon 12 mutation rate of duct lesions in the normal pancreas. Postmortem pancreases from 140 patients were screened for the presence of mucinous cell hypertrophy (MHT), ductal papillary hyperplasia (DPH), adenomatoid ductal hyperplasia (ADH), and squamous metaplasia (SQM). Microdissected cell samples were analyzed for K-ras codon 12 mutations by polymerase chain reaction amplification of exon 1 of the K-ras gene, combined with constant denaturing gel electrophoresis, and analyzed by sequencing. Of the 140 specimens 114 showed duct lesions. The lesions were evenly distributed throughout the pancreas. They were more common beyond the age of 40. MHT was present in 68%, DPH in 36%, ADH in 40%, and SQM in 36% of the cases. K-ras mutations were found in 19 samples from 15 out of 79 pancreases (18%), including all types of duct lesions and a variant of ADH with dense stroma. 67% of the K-ras-positive specimens showed the transition GGT to GAT (8) or GTT (5). Hyperplastic/metaplastic duct changes of the pancreas increase with age, but their distribution pattern in the pancreas differs from that of ductal carcinomas.

Adolescent↗
PubMed1993

Spatial processing and emotionality in aged NMRI mice: a multivariate analysis.

The goal of this study was to investigate possible relationships between different aspects of behavioural decline in aged (17 months) NMRI mice by a multivariate analysis. These mice presented defects in spatial processing both in place learning in a Morris-type water maze and in spontaneous alternation in a Y-maze, as well as showing changes in their behaviour in the elevated plus maze test of fear/anxiety and open-field ambulation. Data were first factor analysed and then correlated on the basis of variable factor scores. The results showed clearly that age-related behavioural changes were independent of each other except between open-field activity measured over 6 min and spatial learning indices in the Morris-type water maze, in that mice performing poorly in the latter were more active in the open field, and between the ratio open/total arms visited in the elevated plus maze task and locomotor activity during the first 2 min of the open-field test. It is proposed that the notion of an allocentric or locale system cannot be applied unitarily to both spatial learning and spontaneous alternation defects, and that activity levels in the aged mice are task dependent and reflect different underlying factors.

Aging↗
PubMed1995

U.S. apartheid and the spread of AIDS to the suburbs: a multi-city analysis of the political economy of spatial epidemic threshold.

We compare mechanisms of AIDS diffusion at the county level from five U.S. central city epicenters into their associated metropolitan regions. Four of the five show an expanding 'hollowed out' center of physically and socially devastated, politically and economically abandoned high density minority neighborhoods, surrounded by rings of relatively affluent majority suburban populations. From these centers AIDS diffuses into the suburbs as a single, spatially extended disease ecosystem. The exception, San Francisco, has not yet experienced the 'hollowing out' process and is, we conclude, a major AIDS epicenter markedly less coupled to its suburbs because of that fact. This may constitute one of the few empirical observations of spatial threshold in epidemiology. Our empirical results contradict the conclusions of a recent National Research Council report that AIDS will be largely confined within marginalized urban populations. In reality U.S. urban apartheid, particularly its continuing disruption of minority social structures, has markedly accelerated the diffusion of AIDS into suburban communities. A widespread program of reform, which rebuilds minority physical and social community structures within both city and suburb, is an essential, but largely unrecognized, component to any serious strategy for the control of AIDS in the United States.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Variation of the spatial position computed by Roentgen Stereophotogrammetric Analysis (RSA) under non-standard conditions.

Roentgen Stereophotogrammetric Analysis (RSA) has been applied to different kinds of research in order to obtain important information in the biomechanics field. Operative requirements change according to the type of investigation and sometimes practical conditions do not always permit one to respect standard specifications. The aim of this paper is to verify the reliability of the system under non-standard conditions, studying the effects of the focus-to-film distance on the determination of 3D co-ordinates of markers. The application of statistical analysis, consisting of two and three way ANalysis Of VAriance (ANOVA), showed that focus-to-film distance is not a significant source of variation, i.e., the system can correctly compute the marker position inside the calibrated space under all conditions of magnification. Since we obtained a fluctuation due to focal distance change of 10(-5) mm (LSD for 95% confidence level), we can assert that this source causes a variation strictly within the limits required by clinical investigations. Thus, this study contributes to improving the flexibility of RSA in clinical applications, making the technical requirements of the radiographic set-up less constraining.

Analysis of Variance↗
PubMed2002

Selective attention to spatial frequency: an ERP and source localization analysis.

OBJECTIVES: Physiological correlates of visual selective attention have been observed by recording ERPs to attended versus ignored target stimuli. Over many such studies, spatial attention has been observed to modulate early sensory components beginning 70 ms after stimulus onset, while effects of selection based on other stimulus features such as color and spatial frequency occur at longer latencies. Together, these findings argue for a primacy of location in early attentional selection. However, there have been some reports suggesting attention effects on short latency sensory-evoked potentials during selection of spatial frequency. The prime objective of the present study was to assess whether or not spatial frequency-dependent potentials are modulated by attention at a latency as early as 70-100 ms. METHODS: Checkerboard patterns were flashed to the subject, one being the target requiring a response. We investigated attentional effects using high-density scalp mapping and inverse dipole modeling. RESULTS: The earliest robust signs of selective attention to spatial frequencies consisted of an occipital selection negativity (OSN) and a frontal selection positivity (FSP). The OSN started at a latency of 140 ms, the FSP somewhat earlier at 120 ms. These attention effects were readily modeled by sources in cortical areas ventrally and laterally to the more primary areas generating the shorter-latency sensory components. CONCLUSIONS: This pattern of results has been found for non-spatial stimulus features in several studies, and is clearly different from the ERP correlates of spatial selection.

Adolescent↗
PubMed1994

Spatially regulated expression of retrovirus-like transposons during Drosophila melanogaster embryogenesis.

Over twenty distinct families of long terminal direct repeat (LTR)-containing retrotransposons have been identified in Drosophila melanogaster. While there have been extensive analyses of retrotransposon transcription in cultured cells, there have been few studies of the spatial expression of retrotransposons during normal development. Here we report a detailed analysis of the spatial expression patterns of fifteen families of retrotransposons during Drosophila melanogaster embryogenesis (17.6, 297, 412, 1731, 3S18, blood, copia, gypsy, HMS Beagle, Kermit/flea, mdg1, mdg3, opus, roo/B104 and springer). In each case, analyses were carried out in from two to four wild-type strains. Since the chromosomal insertion sites of any particular family of retrotransposons vary widely among wild-type strains, a spatial expression pattern that is conserved among strains is likely to have been generated through interaction of host transcription factors with cis-regulatory elements resident in the retrotransposons themselves. All fifteen families of retrotransposons showed conserved patterns of spatially and temporally regulated expression during embryogenesis. These results suggest that all families of retrotransposons carry cis-acting elements that control their spatial and temporal expression patterns. Thus, transposition of a retrotransposon into or near a particular host gene-possibly followed by an excision event leaving behind the retrotransposon's cis-regulatory sequences-might impose novel developmental control on such a host gene. Such a mechanism would serve to confer evolutionarily significant alterations in the spatio-temporal control of gene expression.

Animals↗