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PubMed2002

Cancer induction by radiotherapy: dose dependence and spatial relationship to irradiated volume.

The present study was initiated to identify radiotherapy-related parameters influencing the development of second malignancies. Between 1969 and 1989, about 31000 patients were treated with radiotherapy in Dresden. Of these, 203 were re-admitted for radiotherapy of a newly developed malignancy. Based on completeness of documentation, definition of site of origin and exclusion of recurrent or metastatic tumours, 85 patients were selected for analysis of spatial relation between new tumour and primary treatment fields, and of dose at the site of origin. The majority of second tumours were seen within the margin region of the treatment volume, defined as the volume from 2.5 cm inside to 5 cm outside the margin of the planning target volume (PTV). Fewer than 10% of the second tumours occurred inside the PTV and 11% developed outside the margin region. The majority of second tumours were observed in the volume receiving <6 Gy. Similar results were obtained in a group of 31 patients initially irradiated for benign diseases. This should be considered in radiotherapy, particularly with multiple-field techniques or intensity-modulated radiotherapy, where the volume receiving <6 Gy is substantially increased.

Humans↗
PubMed2006

Inferring colonization history from analyses of spatial genetic structure within populations of Pinus strobus and Quercus rubra.

Many factors interact to determine genetic structure within populations including adult density, the mating system, colonization history, natural selection, and the mechanism and spatial patterns of gene dispersal. We examined spatial genetic structure within colonizing populations of Quercus rubra seedlings and Pinus strobus juveniles and adults in an aspen-white pine forest in northern Michigan, USA. A 20-year spatially explicit demographic study of the forest enables us to interpret the results in light of recent colonization of the site for both species. We assayed 217 Q. rubra seedlings and 171 P. strobus individuals at 11 polymorphic loci using nine allozyme systems. Plant genotypes and locations were used in an analysis of spatial genetic structure. Q. rubra and P. strobus showed similar observed levels of heterozygosity, but Q. rubra seedlings have less heterozygosity than expected. Q. rubra seedlings show spatial genetic clumping of individuals on a scale to 25 m and levels of genetic relatedness expected from the clumped dispersion of half-siblings. In contrast, P. strobus has low levels of genetic relatedness at the smallest distance class and positive spatial genetic structure at scales < 10 m within the plot. The low density of adult Q. rubra outside the study plot and limited, spatially clumped rodent dispersal of acorns is likely responsible for the observed pattern of spatial genetic structure and the observed heterozygote deficit (i.e. a Wahlund effect). We attribute weaker patterns observed in P. strobus to the longer dispersal distance of seeds and the historical overlap of seed shadows from adults outside of the plot coupled with the overlap of seed shadows from younger, more recently established reproductive adults. The study demonstrates the utility of long-term demographic data in interpreting mechanisms responsible for generating contemporary patterns of genetic structure within populations.

Genetic Variation↗
PubMed2026

Spatial proximity sequencing maps developmental dynamics in the germinal center.

Spatial profiling of proteins and protein interactions facilitates understanding of cell functions within tissues and is essential for studies in signaling, immunity, and cancer. We present spatial proximity sequencing (Sprox-seq) for simultaneous profiling of surface proteins, protein complexes, and mRNAs, recording the tissue location of each molecule. Sprox-seq profiled 32 proteins, 528 pairwise interactions, and thousands of mRNAs with spatial resolution across human tonsils and germinal centers. Mapping tissue-wide protein interactions recapitulated RNA-defined tissue architecture but also revealed higher interaction complexity in the light zone. Protein-interaction trajectories uncovered a B cell state transition distinct from that inferred by RNA. Integrated protein-complex and mRNA analysis related spatially enriched complexes with mitotic pathways. Sprox-seq captured cell-cell interactions, such as B cell-follicular dendritic cell interactions mediated by the receptor complex VLA-4-VCAM1. Sprox-seq provides a spatially resolved multi-modal view of cell states and an integrated study of protein and cellular interactions across tissues.

Humans↗
PubMed2006

Feature selectivity in area 21a of the cat.

We compared the feature tuning of neuronal activity in area 21a with the tuning in areas 17/18. Local field potentials and multi-unit activity recorded in alert animals showed similar selectivity to orientation in both areas, higher selectivity to spatial frequencies in areas 17/18 and higher selectivity and tuning significance to temporal frequencies in areas 17/18. In addition, only at sites in areas 17/18 did the local field potential exhibit locking to a horizontal motion pattern extracted from a natural movie. These results suggest that area 21a is concerned with the analysis of spatial features but lacks a faithful representation of temporal features. Hence, they foster the hypothesis that cortical area 21a is part of a ventral form pathway.

Action Potentials↗
PubMed2002

High-throughput imaging of brain gene expression.

Voxelation is a new method for acquisition of three dimensional (3D) gene expression patterns in the brain. It employs high-throughput analysis of spatially registered voxels (cubes) to produce multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. Using microarrays, 24 voxel images of coronal hemisections at the level of the hippocampus of both the normal human brain and Alzheimer's disease brain were acquired for 2000 genes. The analysis revealed a common network of coregulated genes, and allowed identification of putative control regions. In addition, singular value decomposition (SVD), a mathematical method used to provide economical explanations of complex data sets, produced images that distinguished between brain structures, including cortex, caudate, and hippocampus. The results suggest that voxelation will be a useful approach for understanding how the genome constructs the brain.

Adult↗
PubMed2006

CYP707A1 and CYP707A2, which encode abscisic acid 8'-hydroxylases, are indispensable for proper control of seed dormancy and germination in Arabidopsis.

Endogenous abscisic acid (ABA) levels are regulated by both biosynthesis and catabolism of the hormone. ABA 8'-hydroxylase is considered to be the key catabolic enzyme in many physiological processes. We have previously identified that four members of the Arabidopsis (Arabidopsis thaliana) CYP707A gene family (CYP707A1 to CYP707A4) encode ABA 8'-hydroxylases, and that the cyp707a2 mutants showed an increase in ABA levels in dry and imbibed seeds. In this study, we showed that the cyp707a1 mutant accumulated ABA to higher levels in dry seeds than the cyp707a2 mutant. Expression analysis showed that the CYP707A1 was expressed predominantly during mid-maturation and was down-regulated during late-maturation. Concomitantly, the CYP707A2 transcript levels increased from late-maturation to mature dry seed. Phenotypic analysis of single and double cyp707a mutants indicates that the CYP707A1 is important for reducing ABA levels during mid-maturation. On the other hand, CYP707A2 is responsible for the regulation of ABA levels from late-maturation to germination. Moreover, CYP707A1 and CYP707A3 were also shown to be involved in postgermination growth. Spatial expression analysis suggests that CYP707A1 was expressed predominantly in embryo during mid-maturation, whereas CYP707A2 expression was detected in both embryo and endosperm from late-maturation to germination. Our results demonstrate that each CYP707A gene plays a distinct role during seed development and postgermination growth.

Abscisic Acid↗
PubMed1997

Empirical analyses of BOLD fMRI statistics. II. Spatially smoothed data collected under null-hypothesis and experimental conditions.

In the companion to this paper (E. Zarahn, G. K. Aguirre, and M. D'Esposito, 1997, NeuroImage, 179-197), we describe an implementation of a general linear model for autocorrelated observations in which the voxel-wise false-positive rates in fMRI "noise" datasets were stabilized and brought close to theoretical values. Here, implementations of the model are tested for use with statistical parametric mapping analysis of spatially smoothed fMRI data. Analyses using varying models of intrinsic temporal autocorrelation and either including or excluding a global signal covariate were conducted upon human subject data collected under null hypothesis as well as under experimental conditions. We found that smoothing with an empirically derived impulse response function (IRF), combined with a model of the intrinsic temporal autocorrelation in spatially smoothed fMRI data, resulted in a map-wise false-positive rate which did not exceed a 5% level when a nominal alpha = 0.05 tabular threshold was applied. Use of other models of intrinsic temporal autocorrelation resulted in map-wise false-positive rates that significantly exceeded this level. fMRI data collected while subjects performed a behavioral task were used to examine (a) task-dependent global signal changes and (b) the dependence of sensitivity on the temporal smoothing kernel and inclusion/exclusion of a global signal covariate. The global signal changes within an fMRI dataset were shown to be influenced by the performance of a behavioral task. However, the inclusion of this measure as a covariate did not have an adverse affect upon our measure of sensitivity. Finally, use of an empirically derived estimate of the IRF of the system was shown to result in greater map-wise sensitivity for signal changes than the use of a broader (in time) Poisson (parameter = 8 s) kernel.

Adult↗
PubMed2003

Atomistic observation and simulation analysis of spatio-temporal fluctuations during radiation-induced amorphization.

We performed a dynamical-atomistic study of radiation-induced amorphization in the NiTi intermetallic compound using in situ high-resolution high-voltage electron microscopy and molecular dynamics simulations in connection with image simulation. Spatio-temporal fluctuations as non-equilibrium fluctuations in an energy-dissipative system, due to transient atom-cluster formation during amorphization, were revealed by the present spatial autocorrelation analysis.

Journal Article↗
PubMed2001

Regional variation in the incidence of schizophrenia in Finland: a study of birth cohorts born from 1950 to 1969.

BACKGROUND: We investigated whether there is regional variation in the incidence of schizophrenia and if so. whether it is caused by urban-rural differences, larger spatial clustering, or both. To control for the effect of migration, we examined regional variation in the incidence according to place of birth. METHODS: Finnish birth cohorts born from 1950 to 1969 were followed in the National Hospital Discharge Register from 1969 until 1991, and all cases of schizophrenia (ICD-8 or ICD-9 295) were identified (N = 14828). Forty-eight of the 559 municipalities were classified as urban and 25% of the Finnish population lived in these municipalities in 1960. For the analysis of spatial clustering, municipalities were grouped into 57 functional small-areas. We used Poisson regression model with the number of births of individuals who later developed schizophrenia as a response variable, and place of birth (urban/rural), birth cohort (1950-54, 1955-9, 1960-64, and 1965-9), functional small-area units, and sex as response variables. RESULTS: The incidence was slightly higher among the rural-born in the oldest birth cohort. In the other cohorts, it was higher among the urban-born, and the difference between urban and rural born increased in the youngest cohorts. Significant spatial clustering of schizophrenia was observed in eastern Finland. CONCLUSIONS: Urban birth is a risk factor for schizophrenia in Finland in cohorts born since 1955. However, genuine spatial clustering of schizophrenia in eastern Finland was also observed, possibly caused by genetic isolation.

Adolescent↗
PubMed1985

Idiotope mapping on the variable region of an antibody clonotype produced by normal (nonmalignant) human B cells.

Human anti-N-acetyl-D-glucosamine (GlcNAc) antibodies were prepared by affinity chromatography from serum of a healthy donor (MSS). They were heterogeneous but contained a unique antibody clonotype (1A) representing 7% of all anti-GlcNAc antibodies. Out of a series of monoclonal anti-idiotopic antibodies (anti-Id mAb), we identified five antibodies that bound to clonotype 1A as shown by isoelectric focusing and Western blotting. Two of them were specific for clonotype 1A (10F59 and 13F15), thus indicating its clonal origin. However, three anti-Id mAb (16F433, 16F539, and 16F812) bound to various additional portions of anti-GlcNAc antibodies of donor MSS. With the exception of one mAb, all anti-Id mAb have very similar relative affinities to clonotype 1A, so results from competition experiments between the different antibodies and between each antibody and antigen should reveal spatial relationships between the corresponding Id and between each Id and the antigen-combining site. The results show a consistent topography of Id on the V-region of clonotype 1A. Id 59, 812, and 433 were found to be arranged in one cluster (cluster I), whereas Id 15 and 539 belonged to a second cluster (cluster II). Cluster I resides completely in the antigen-combining site, whereas only Id 15 of cluster II weakly overlaps with the binding site. Our study demonstrates an analysis of spatial relationships of Id expressed on a human antibody clonotype. To our knowledge, this is the first demonstration of Id mapping on antibodies produced by a normal (nonmalignant) B cell clone that should be accessible to regulatory signals. Such analysis may contribute to a more detailed characterization of anti-Id mAb, and may provide additional information for a better understanding of their immunoregulatory effects.

Acetylgalactosamine↗
PubMed1992

The value of pixel per pixel multiharmonic Fourier analysis to assess left ventricular function.

Left ventricular systolic and diastolic function can be assessed by peak ejection and filling rates and their time of occurrence. These parameters can be calculated using two different methods: from the global left ventricular time-activity curve analysed with a four harmonic Fourier fit and from each pixel time-activity curve analysed with two and three harmonics (the values being averaged over the left ventricular region of interest). In both cases, values were normalized for heart rate and end diastolic counts. A study was conducted in a series of 11 patients (six without and five with a previous myocardial infarction but a normal left ventricular function) examined at baseline and during an i.v. dobutamine infusion, at a dose known to increase both peak ejection and filling rates. During dobutamine infusion, analysis of global left ventricular time-activity curve demonstrated a statistically significant increase in both peak ejection and filling rates, but the local analysis showed a more significant increase of these parameters. To assess ventricular function, a local harmonic analysis can be used and appears to be a more sensitive approach than analysis of the global left ventricular time-activity curve. The local analysis provides spatial mapping and a histogram of the parameters which can be used as parametric images to describe systolic and diastolic function.

Dobutamine↗
PubMed2006

Analysis of the spatio-temporal and semantic aspects of land-cover/use change dynamics 1991-2001 in Albania at national and district levels.

In the turmoil of a rapidly changing economy the Albanian government needs accurate and timely information for management of their natural resources and formulation of land-use policies. The transformation of the forestry sector has required major changes in the legal, regulatory and management framework. The World Bank financed Albanian National Forest Inventory project provides an analysis of spatially explicit land-cover/use change dynamics in the period 1991-2001 using the FAO/UNEP Land Cover Classification System for codification of classes, satellite remote sensing and field survey for data collection and elements of the object-oriented geo-database approach to handle changes as an evolution of land-cover/use objects, i.e. polygons, over time to facilitate change dynamics analysis. Analysis results at national level show the trend of natural resources depletion in the form of modifications and conversions that lead to a gradual shift from land-cover/use types with a tree cover to less dense tree covers or even a complete removal of trees. Policy failure (e.g., corruption, lack of law enforcement) is seen as the underlying cause. Another major trend is urbanisation of areas near large urban centres that change urban-rural linkages. Furthermore, after privatisation agricultural areas increased in the hills where environmental effects may be detrimental, while prime agricultural land in the plains is lost to urbanisation. At district level, the local variability of spatially explicit land-cover/use changes shows different types of natural resources depletion. The distribution of changes indicates a regional prevalence, thus a decentralised approach to the natural resources management could be advocated.

Albania↗
PubMed2026

Extracellular vesicle miR-93-5p cargo regulates glomerular endothelial cell damage in Alport syndrome.

Modulation of miRNA expression in glomerular cells is associated with renal disease. Here, we investigated the role of miR-93-5p in mitigating glomerular damage in Alport syndrome and whether the disease-modifying activity of extracellular vesicles from human amniotic fluid stem cells (hAFSC-EVs) is mediated by their miR-93-5p cargo. We identified downregulation of miR-93-5p specifically in glomerular endothelial cells in Alport syndrome along disease progression. Silencing of miR-93-5p in hAFSC-EVs changed the transcriptomic and proteomic profile, regulating EV disease-modifying activity. Compared with naive hAFSC-EVs, silenced hAFSC-EVs did not rescue glomerular endothelial function in vitro and did not restore kidney function in vivo. We established that hAFSC-EVs regulate VEGFR1 and VEGFR2 signaling by miR-93-5p cargo transfer, highlighting that miR-93-5p can restore glomerular endothelial cell biology. Spatial transcriptomics analysis of hAFSC-EV-injected kidneys showed that these EVs can reverse pathways altered during disease progression by stimulating proregenerative processes, specifically in the glomerulus, by regulating miR-93-5p targets. Alteration of glomerular endothelial cell transcriptomics and miR-93-5p targets was also confirmed in biopsies of patients with Alport syndrome using spatial molecular imaging. We demonstrated the critical role of miR-93-5p in glomerular endothelial cells and the capability of hAFSC-EVs to regulate miR-93-5p and its targets in Alport syndrome.

Humans↗
PubMed2005

[Spatial variance characters of urban synthesis pattern indices at different scales].

Scale holds the key to understand pattern-process interactions, and indeed, becomes one of the corner-stone concepts in landscape ecology. Geographic Information System and remote sensing techniques provide an effective tool to characterize the spatial pattern and spatial heterogeneity at different scales. As an example, these techniques are applied to analyze the urban landscape diversity index, contagion index and fractal dimension on the SPOT remote sensing images at four scales. This paper modeled the semivariogram of these three landscape indices at different scales, and the results indicated that the spatial variance characters of diversity index, contagion index and fractal dimension were similar at different scales, which was spatial dependence. The spatial dependence was showed at each scale, the smaller the scale, the stronger the spatial dependence. With the scale reduced, more details of spatial variance were discovered. The contribution of spatial autocorrelation of these three indices to total spatial variance increased gradually, but when the scale was quite small, spatial variance analysis would destroy the interior structure of landscape system. The semivariogram models of different landscape indices were very different at the same scale, illuminating that these models were incomparable at different scales. According to above analyses and based on the study of urban land use structure, 1 km extent was the more perfect scale for studying the spatial variance of urban landscape pattern in Shanghai. The spatial variance of landscape indices had the character of scale-dependence, and was a function of scale. The results differed at different scales we chose, and thus, the influence of scales on pattern could not be neglected in the research of landscape ecology. The changes of these three landscape indices displayed the regularity of urban spatial structure at different scales, i. e., they were complicated and no regularity at small scale, polycentric at moderate scale, and circle-zoning at big scale.

City Planning↗
PubMed2006

Visualization, reconstruction, and integration of neuronal structures in digital brain atlases.

Brain atlases are used in neuroanatomy to define the spatial layout of neuronal structures. Their digital variant can serve as a database and common reference frame for integrating data from different biological experiments. This article presents an overview of methods for three-dimensional visualization of neuroanatomical image data, reconstructing neuronal structures from image data, creating digital brain atlases, and registering data in an atlas. This enables analysis of spatial relations between individual structures imaged in different experiments as well as between these structures and the atlas.

Animals↗
PubMed2006

Distributed strain measurement with millimeter-order spatial resolution based on Brillouin optical correlation domain analysis.

Distributed strain sensing with millimeter-order spatial resolution is demonstrated in optical fibers based on Brillouin optical correlation domain analysis. A novel beat lock-in detection scheme is introduced to suppress background noises coming from the reflection of Brillouin pump waves. The Brillouin frequency shifts of 3 mm fiber sections are successfully measured with a theoretical spatial resolution of 1.6 mm.

Journal Article↗
PubMed1998

Software implementation of statistical methods for the analysis of structure and patterns in neuroanatomical objects.

Neuroanatomical research has greatly benefited from the availability of a large number of cell-specific and region-specific molecular markers. In fact, the analysis of spatial patterns of gene expression in individual cells or patterns within cell populations often provides an inroad into understanding the functional significance of distinct structures. However, it can be difficult to discern whether the arrangement of different morphologically or biochemically defined structures represents a defined pattern. To address this issue, we adapted a series of established statistical procedures for the analysis of uni- and bivariate point patterns in histological specimens. We implemented these statistical procedures in an easy-to-use computer program. The methods are scale independent and easy to expand for various applications. The utility of this approach is demonstrated with examples from tissue sections and cultured cells at the light and electron microscopical levels.

Actins↗
PubMed2005

Sequestration of serum response factor in the hippocampus impairs long-term spatial memory.

The formation of long-term memory has been shown to require protein kinase-mediated gene expression. One such kinase, mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), can lead to the phosphorylation of serum response factor (SRF) and Elk-1, enhancing the expression of target genes. However, a direct involvement of these transcription factors in memory storage has not been demonstrated. We have employed an oligonucleotide decoy technique to interrogate SRF and Elk-1. Previously, it has been shown that intra-amygdalal infusion of small double-stranded decoy oligonucleotides for nuclear factor-kappaB (NFkappaB) can impair long-term memory for fear-potentiated startle. Using this approach, we found that intra-hippocampal infusion of NFkappaB decoy oligonucleotides also impairs long-term spatial memory, consistent with a role for this factor in long-term memory storage. Decoy oligonucleotides containing the binding site for SRF, as confirmed by shift-western, did not influence memory acquisition but impaired long-term spatial memory. Analysis of search behavior during the transfer test revealed deficits consistent with a loss of precise platform location information. In contrast, oligonucleotides with a binding site for either Elk-1 or another target of ERK activity, SMAD3/SMAD4, did not interfere with memory formation or storage. These findings suggest that SRF-mediated gene expression is required for long-term spatial memory.

Animals↗