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Retest reliability of spatiotemporal gait parameters in children and adults.

The objective of the study was to assess the retest-reliability of ten different gait parameters in healthy children (n=12; age 6-7 years) and adults (n=12; age 21-35 years) during free-speed locomotion on a simple walkway. Further the intra-subject variability of the stride dimensions was checked. On two occasions, spatial gait parameters were measured by footprint analysis, temporal dimensions were recorded using video-analysis. For spatial gait parameters, correlation coefficients (ICC, Pearson's r) between the test and the retest results were found to be high in adults and satisfying in children. The temporal parameters were less consistent. Generally the within-trial variability was higher in children than in adults. Conclusions: (i) The retest reliability for the measurement of the spatial gait parameters can be judged as high. (ii) For gait analysis in children it should be taken into account that gait parameters are more variable from trial to trial than in adults. Copyright 1997 Elsevier Science B.V.

Journal Article↗

Analysis of temporal and spatial expression of the CcaR regulatory element in the cephamycin C biosynthetic pathway using green fluorescent protein.

The DNA-binding capability of a key secondary metabolite regulatory element (CcaR) in the Streptomyces clavuligerus cephamycin C pathway was investigated by gel mobility retardation and DNase I footprinting analysis. These results revealed that CcaR specifically binds to the promoter region of the lysine-epsilon-aminotransferase gene (lat). Green fluorescent protein (GFP) was subsequently used as a reporter to analyse in vivo expression of CcaR. The corresponding isogenic strain containing ccaR:gfp in the chromosome produced cephamycin C at levels similar to those of wild-type S. clavuligerus. Confocal laser scanning microscopy revealed that expression of CcaR in liquid culture was temporally dynamic and spatially heterogeneous in S. clavuligerus mycelia. The highly fluorescent seed culture mycelia quickly lost fluorescence upon inoculation into fresh culture medium. The characteristic green colour reappeared in a small portion of mycelia during mid-exponential growth phase. As the culture aged, the population expressing CcaR expanded, and the expression level increased. This was followed by a reduction in the CcaR-expressing population towards the end of the culture period. During peak expression, CcaR was distributed uniformly in mycelia, but became localized distal to the chromosome when the culture entered stationary phase. In solid phase analysis, abundant CcaR expression was evident in the substrate mycelia, but was completely absent in aerial hyphae. These results show regulatory linkage between ccaR and lat, whose expression profile showed a similar spatial decoupling between morphogenesis and antibiotic production. In addition, visualizing CcaR within S. clavuligerus mycelia demonstrates a distinct pattern of localization over the course of physiological differentiation.

Alcohol Oxidoreductases↗

Rapid detection of spatial pattern by Fourier analysis.

Fast Fourier transform analysis can be used to accurately and rapidly detect pattern in large two-dimensional arrangements of points, such as the locations of cells in culture or plants in a unit square. We present here a sample study of pattern in spatial random point processes. This is evidently the first time that Fourier transform-based cross-correlation techniques have been applied to the analysis of point processes of biological origin. Radial profiles of the power spectra and autocorrelation estimates revealed a nearly constant interpore distance of 0.49 +/- 0.04 mm in the locations of eccrine gland pores on the surface of human skin. Additionally, gland-free areas may exist near hair follicles.

Algorithms↗

Multivariate analysis of putative measures of activity, exploration, emotionality, and spatial behavior in the hooded rat (Rattus norvegicus).

Hooded rats were tested in six situations representing the variables of activity, exploration, emotionality, and spatial preference, detection of change, and learning. The activity, exploration, and emotionality variables and spatial variables were analyzed in separate multivariate analyses, followed by an analysis of the entire set. The first of these resulted in four components: activity, exploration and emotionality, reactivity to handling, and autonomic reactivity (defecation). Four components, defined by the following variables, emerged from the spatial analysis: (a) the tendency to circle, circling direction, and spatial learning; (b) heading error in spatial learning and reversal and open-field directional preference; (c) spatial reversal and direction of turn to escape restraint; and (d) detection of change in spatial arrangement and directional preference in the detection task. The final analysis investigated relations between the activity, exploration, and emotionality variables and the spatial variables, finding only two. The clear dimensionality of these behavioral repertoires emphasizes how important it is to recognize the distinctions among them.

Animals↗

DNAPL source depletion: linking architecture and flux response.

The relationship between dense non-aqueous phase liquid (DNAPL) mass reduction and contaminant mass flux was investigated experimentally in four model source zones. The flow cell design for the experiments featured a segmented extraction well that allowed for analysis of spatially resolved flux information. This flux information was coupled with image analysis of the NAPL spatial distribution to investigate the relationship between flux and the up-gradient NAPL architecture. Results indicate that in the systems studied, the relationship between DNAPL mass reduction and contaminant mass flux was primarily controlled by the NAPL architecture. A specific definition of NAPL architecture was employed where the source zone is resolved into a collection of streamtubes with spatial variability in NAPL saturation along each streamtube integrated and transformed into an effective NAPL content for each streamtube. The distribution of NAPL contents among the streamtubes (NAPL architecture) controlled dissolution dynamics. Two simplified models, a streamtube model and an effective Damkohler number model, were investigated for their ability to simulate dissolution dynamics.

Kinetics↗

Spatial low frequency pattern analysis in positron emission tomography: a study between normals and schizophrenics.

Using the two-dimensional Fourier transform and the brain's centroidal principal axis, a method is developed for the analysis of PET metabolic brain images without the use of predefined anatomic regions of interest. We applied the method to images from a group of 11 normal and 12 medicated schizophrenics tested under resting conditions and under a visual task. A cortical/subcortical spatial pattern was found to be significant in two directions; anterior/posterior and chiasmatic (left-anterior/right-posterior). The best individual clinical classification (Jackknife classification) occurred under visual task at two axial brain levels: at the basal ganglia with correct classification rates of 91% and 84%, while the cerebellum had rates of 82% and 92%. These high classification rates were obtained using only the four coefficients of the lowest spatial frequency. These results point to the generalized brain dysfunction of regional glucose metabolism in chronic medicated schizophrenics both at rest and at a visual image-tracking task.

Analysis of Variance↗

Microphone array measurement system for analysis of directional and spatial variations of sound fields.

A measurement system has been developed that is capable of analyzing the directional and spatial variations in a reverberant sound field. A spherical, 32-element array of microphones is used to generate a narrow beam that is steered in 60 directions. Using an omnidirectional loudspeaker as excitation, the sound pressure arriving from each steering direction is measured as a function of time, in the form of pressure impulse responses. By subsequent analysis of these responses, the variation of arriving energy with direction is studied. The directional diffusion and directivity index of the arriving sound can be computed, as can the energy decay rate in each direction. An analysis of the 32 microphone responses themselves allows computation of the point-to-point variation of reverberation time and of sound pressure level, as well as the spatial cross-correlation coefficient, over the extent of the array. The system has been validated in simple sound fields in an anechoic chamber and in a reverberation chamber. The system characterizes these sound fields as expected, both quantitatively from the measures and qualitatively from plots of the arriving energy versus direction. It is anticipated that the system will be of value in evaluating the directional distribution of arriving energy and the degree and diffuseness of sound fields in rooms.

Amplifiers, Electronic↗

Perception of breast cancer: eye-position analysis of mammogram interpretation.

RATIONALE AND OBJECTIVE: The author performed this study to determine how image-based elements are translated into decisions by radiologists with different levels of experience in the reading of mammograms. MATERIALS AND METHODS: Three full-time mammographers and four radiology residents read 40 two-view mammogram cases. The observers' eye position was tracked while they searched the mammograms for malignancies. Spatial frequency analysis was performed to relate what the observers reported with where they looked. RESULTS: Statistically significant differences were found between lesion-containing areas that attracted visual attention and were correctly interpreted and those that were visually inspected but not reported. In addition, an artificial neural network was successfully trained to map the image characteristics in the visually selected areas on a mammogram and to linkthem to a likely decision by the observer. CONCLUSION: Spatial frequency analysis can be used to derive trends for how mammographers and radiology residents will respond to mammograms.

Analysis of Variance↗

Analysis of temporal and spatial patterns of rat vestibular hair cell differentiation by tritiated thymidine radioautography.

The location in time and space of the terminal mitoses of type I and type II sensory hair cells (HCI and HCII) of the developing crista ampullaris in rat lateral semicircular canal and macula utriculi was determined by radioautographs of specimens exposed to tritiated thymidine from the 13th to the 20th day of gestation. Qualitative analysis and statistical treatment of the percentages of labeled HCI and HCII show that the terminal mitoses occur first in the macula utriculi with a maximum percentage of the 14th day of gestation, for the HCI, and on the 15th day of gestation, for the HCII. In the lateral crista, the maximum percentage of labeled HCI occurs on the 17th and 18th day of gestation and on the 19th day of gestation for the HCII. A spatial distribution of this labeling activity is also described: the older cells are located at the top of the crista and at the level of the striola of the macula utriculi while the younger cells are found at the bottom of the crista and on the sides of the utricle. A study of the vestibular receptors in the fetuses shows that synaptic contacts already exist on the 18th day of gestation in the macula utriculi at the level of the striola and on the 19th day at the top of the crista; the cells situated on the periphery are still immature. The first hair cells to undergo their terminal mitoses are, therefore, connected first. These results also suggest that the two types of cells are genetically programmed and that the HCI start functioning first during the development of the labyrinth.

Acoustic Maculae↗

Spatial and dye correlation analysis of intracellular Ca2+ distribution.

Intracellular Ca2+ is an important regulator of many cellular processes. Besides ion channels and transporters in the plasmalemma, changes in [Ca]i can be mediated by uptake and release mechanisms of internal organelles. Theoretical and experimental procedures are developed aiming to reveal the distribution of internal Ca2+ pools and their role in generating complicated spatial patterns of [Ca]i gradients. Cultured pyramidal neurons from rat hippocampus were loaded with Ca(2+)-sensitive fluorescent dyes, fura-2 and fluo-3. Cell images were partitioned according to pixel amplitude and highlighted pictures were characterized by their intensity, relative area and connectivity. This approach facilitates the localization of the sites of Ca2+ release from internal stores induced by application of different agents. After each trial, neurons were stained with dyes, acridine orange or DiOC6, which bind preferentially to nucleus and endoplasmic reticulum. A correlation between images confirmed the spatial localization of Ca2+ release sites. Application of the partition procedure also gave a clear evidence for the importance of Ca2+ influx in the mechanism of [Ca]i oscillations.

Aniline Compounds↗

Spatial genetic structure of northern pike (Esox lucius) in the Baltic Sea.

The genetic relationships among 337 northern pike (Esox lucius) collected from the coastal zone of the central Baltic region and the Finnish islands of Aland were analysed using five microsatellite loci. Spatial structure was delineated using both traditional F-statistics and individually based approaches including spatial autocorrelation analysis. Our results indicate that the observed genotypic distribution is incompatible with that of a single, panmictic population. Isolation by distance appears important for shaping the genetic structure of pike in this region resulting in a largely continuous genetic change over the study area. Spatial autocorrelation analysis (Moran's I) of individual pairwise genotypic data show significant positive genetic correlation among pike collected within geographical distances of less than c. 100-150 km (genetic patch size). We suggest that the genetic patch size may be used as a preliminary basis for identifying management units for pike in the Baltic Sea.

Animals↗

Real-time quantitative PCR analysis of temporal-spatial alterations in gene expression after spinal cord contusion.

Rat spinal cord contusion injury models the histopathology associated with much clinical spinal cord injury (SCI). Studies on altered gene expression after SCI in these models may identify therapeutic targets for reducing secondary injury after the initial trauma and/or enhancing recovery processes. However, complex spatial and temporal alterations after injury could complicate interpretation of changes in gene expression. To test this hypothesis, we selected six genes and studied their temporal and spatial patterns of expression at 1 h, 1, 3 and 7 days after a standardized spinal cord contusion produced by a weight drop device (10 g x 25 mm at T8). Real-time RT-PCR using TaqMan probes was employed to quantify mRNA for proteolipid protein, glyceraldehyde-3-phosphate dehydrogenase, glial fibrillary acidic protein, nestin, and the GluR2 and NR1 subunits of glutamate receptors. We found widely different temporal and spatial patterns of altered gene expression after SCI, including instances of opposing up- and down-regulation at different locations in tissue immediately adjacent to the injury site. We conclude that greater use of the reliable and extremely sensitive technique of quantitative real-time PCR for regional tissue analysis is important for understanding the altered gene expression that occurs after CNS trauma.

Animals↗

Spatial organization at the cell surface.

Approaches are described for analysis of spatial organization of cell surface structure. Extraction of cells with nonionic and ionic detergents, chelating and chaotropic agents, salts, and reducing agents results in selective solubilization of surface proteins. Bisimidate disulfide-containing crosslinking reagents produce complexes containing surface proteins which can be analyzed by subsequent dissociation of the complexes. Disulfide-bonded complexes are also found without addition of crosslinkers, and reducing agents aid in extracting surface proteins. These results suggest a possible role for disulfide bonds in cell surface organization. Immunofluorescent staining of cells with antisera to LETS protein and to actin reveals fibrillar structures which survive NP40 extraction. These results indicate a complex organization at the cell surface which is amenable to analysis by permutations of the methods described.

Animals↗

Domains in cell plasma membranes investigated by near-field scanning optical microscopy.

Near-field scanning optical microscopy (NSOM) uses the near-field interaction of light from a sharp fiber-optic probe with a sample of interest to image surfaces at a resolution beyond the diffraction limit of conventional optics. We used NSOM to image fluorescently labeled plasma membranes of fixed human skin fibroblasts, either dried or in buffer. A patchy distribution of a fluorescent lipid analog suggestive of lipid domains was observed in the fixed, dried cells. The sizes of these patches were consistent with the sizes of domains implied by fluorescence photobleaching recovery measurements. Patches of fluorescent lipid analog were not spatially correlated with patches of transmembrane proteins, HLA class I molecules labeled with fluorescent antibody; the patchiness of the HLA class I molecules was on a smaller scale and was not localized to the same regions of membrane as the lipid analog. Sizes of HLA patches were deduced from a two-dimensional spatial autocorrelation analysis of NSOM images that resolved patches with radii of approximately 70 and approximately 600 nm on fixed, dried cells labeled with IgG and 300-600 nm on cells labeled with Fab and imaged in buffer. The large-size patches were also resolved by far-field microscopy. Both the spatial autocorrelation analysis and estimates from fluorescence intensity indicate that the small patches seen on fixed, dried cells contain approximately 25-125 HLA-I molecules each.

Cell Line↗

Mental representations of perspective and spatial relations from diagrams and models.

In previous research (D. J. Bryant, B. Tversky, & N. Franklin, 1992; N. Franklin & B. Tversky, 1990), the authors showed that spatial knowledge conveyed by descriptions and direct experience induces participants to take the perspective of a character surrounded by objects. In this study, the authors used models and diagrams to convey the same information. With models, as with descriptions and experience, participants adopted the character's perspective (the spatial framework analysis). With diagrams, participants took an outside perspective (the intrinsic computation analysis). Even when informationally equivalent, different depictions made salient different aspects of the world. When instructed, however, participants were able to take either the inside or the outside perspective in memory for both diagrams and models. Depth cues in depictions also govern participants' perspective. When diagrams contained rich pictorial depth cues, participants used the spatial framework analysis, and when models were viewed without access to depth cues, participants relied on the intrinsic computation analysis.

Adult↗

Noninvasive quantification of regional ventricular function in rats: assessment of serial change and spatial distribution using ultrasound strain analysis.

BACKGROUND: The optimal method for quantitative assessment of regional ventricular function in rats remains unclear. The goal of this study was to investigate the use of ultrasonic strain rate (SR) and strain analysis in evaluating the serial change and spatial distribution of regional contractile function in rats. METHODS: In all, 22 anesthetized rats underwent incremental dobutamine infusion (protocol 1) for assessment of serial change or underwent coronary ligation (protocol 2) for assessment of spatial distribution. For protocol 1, the serial change of systolic SR and strain during dobutamine was measured in the posterior myocardium on the short-axis view, and the systolic strain was compared with the percent change in wall thickening. For protocol 2, the spatial distribution of strain profile was analyzed in normal, peripheral ischemic, and central ischemic regions that were identified by myocardial contrast echocardiography. RESULTS: In protocol 1, the incremental dobutamine infusion resulted in a gradual increase in peak systolic SR. In contrast, peak systolic strain increased with low-dose dobutamine but tended to decrease for higher doses of dobutamine. Further, the serial change of peak systolic strain corresponded to changes in percent change in wall thickening, but the strain values were always lower than percent change in wall thickening. In protocol 2, the strain profile indicated postsystolic thickening in the peripheral ischemic region and indicated systolic wall thinning in the central ischemic region. CONCLUSIONS: Ultrasonic determination of SR and strain is an accurate and noninvasive method of quantitation of the serial change and spatial distribution of regional contractile function in rats.

Animals↗

Voxelation and gene expression tomography for the acquisition of 3-D gene expression maps in the brain.

Voxelation and gene expression tomography or GET are novel methods for the high-throughput acquisition of gene expression patterns in the mammalian brain. Voxelation employs analysis of spatially registered voxels (cubes), while GET employs analysis of sets of parallel slices rotated about multiple independent axes of rotation. Both methods employ reconstruction of the data to result in multiple volumetric maps of gene expression analogous to those obtained from biomedical imaging techniques. Here, we describe the methodologies underlying voxelation and GET and briefly outline the insights that can be obtained from these approaches.

Animals↗

SPC: a SPectral Component approach leveraging Identity-by-Descent graphs to address recent population structure in genomic analysis.

Population structure is a well-known confounder in statistical genetics, particularly in genome-wide association studies (GWAS), where it can lead to inflated test statistics and spurious associations. Traditional methods, such as principal components (PCs), commonly used to adjust for population structure, are limited in capturing fine-scale, non-linear patterns that arise from recent demographic events - patterns that are crucial for understanding rare variant effects. To address this challenge, we propose a novel method called SPectral Components (SPCs), which leverages identity-by-descent (IBD) graphs to capture and transform local, non-linear fine-scale population structure into continuous representations that can be seamlessly integrated into genetic analysis pipelines. Using both simulated datasets and empirical data from the UK Biobank (N ≈ 420,000), we demonstrate that SPCs outperform PCs in adjusting for fine-scale population structure. In simulations, SPCs explained over 90% of the fine-scale population structure with fewer components, while PCs captured less than 5%. In the UK Biobank, SPCs reduced the inflation of p-values in the GWAS of an environmental-driven phenotype by 12% compared to PCs, while maintaining a similar performance to PCs in height, a highly heritable phenotype. Additionally, SPCs improved rare variant association analyses, reducing genomic inflation (e.g., from 7.6 to 1.2 in one analysis), and provided more accurate heritability estimates. Spatial autocorrelation analysis further confirmed the ability of SPCs to account for environmental effects, reducing Moran's I for both environmental and heritable phenotypes more effectively than PCs. Overall, our findings demonstrate that SPCs provide a robust, scalable adjustment for recent population structure, offering a powerful alternative or complement to PCs in large-scale biobank studies.

GWAS↗