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PubMed2005

The statistical analysis of spatially clustered genes under the maximum gap criterion.

Statistical validation of gene clusters is imperative for many important applications in comparative genomics which depend on the identification of genomic regions that are historically and/or functionally related. We develop the first rigorous statistical treatment of max-gap clusters, a cluster definition frequently used in empirical studies. We present exact expressions for the probability of observing an individual cluster of a set of marked genes in one genome, as well as upper and lower bounds on the probability of observing a cluster of h homologs in a pairwise whole-genome comparison. We demonstrate the utility of our approach by applying it to a whole-genome comparison of E. coli and B. subtilis. Code for statistical tests is available at.

Bacillus subtilis↗
PubMed2004

Early and cost-effective identification of high risk/priority control areas in foot-and-mouth disease epidemics.

Geo-referenced data from the 2001 Uruguayan foot-and-mouth disease (FMD) epidemic were explored to assess whether spatial analysis could lead to cost-benefit based policies. Four variables were analysed: (i) location and size of 4022 individual rural land parcels, of which 574 were infected over 60 days, (ii) animal density, (iii) percentage of dairy farms per county, and (iv) road density. Each variable was categorized into two to five classes (e.g. small/medium/large) and the proportion of cases per class reported at days 1-3 of the epidemic was compared with that reported at days 4-6. A higher proportion of cases was found at days 4-6 than at days 1-3 in areas with: small and medium size land parcels, high animal density, > 20% farms specialized in dairy production, and high road density (P < 0.03 for each). Each of these classes showed a greater proportion of cases at days 7-60 than the proportion of the total territory covered by each class's area (early case concentration ratios: 1.14-1.37). Land parcel clusters were indicated by Moran's I-test (P < 0.01). A new region was constructed by intersecting the four spatial classes associated with higher proportions of cases at days 4-6. At days 7-60, this region included 50.4% of all cases and represented 30.6% of the territory under study (final case concentration ratio: 1.65). The final area per case in this region was at least 33% lower and covered at least 45% less territory than any of the four single-variable approaches. Bio-statistical, multivariate spatial analysis of early cases may greatly increase the efficiency of epidemiologic policy.

Animal Husbandry↗
PubMed1989

Spatial pattern analysis reveals similarities between amphetamine conditioned and unconditioned locomotion.

The repeated injection of drugs which increase locomotion, paired with a distinctive testing environment, has been shown to result in conditioned hyperactivity upon subsequent exposure to the environment alone. Unknown, however, are the form and characteristics of the behavioral response that makes up the conditioned hyperactivity. Conditioned and unconditioned locomotor responses in rats were compared with a computerized Behavioral Pattern Monitor (BPM), a system which provides detailed information regarding the amount and qualitative patterning of locomotor activity and investigatory responses. After an initial 2h exposure to the BPM chambers (baseline day), rats were randomly assigned into one of two groups and injected each day with saline or 0.75mg/kg amphetamine (AMPH) prior to placement in the BPM chambers for a 2h experimental session. Rats were then returned to their home cages and injected with the alternate solution. This procedure was repeated for 5 days, and on the sixth day all rats were injected with saline prior to placement in the BPM. Rats that had received AMPH/BPM pairings exhibited significant increases in horizontal locomotion, rearing and investigatory holepokes on the test day compared to rats that received saline/BPM pairings. The AMPH group also exhibited an increased sensitivity to a physical movement of the test chambers. Analyses of the daily locomotor paths for each rat using transition matrices revealed that the conditioned activity measured on the test day resembled the last AMPH day more than either the first AMPH day or the predrug baseline day. These descriptive measures of each animal's spatial patterns of locomotion suggest that the particular pattern induced by AMPH in each animal stabilized over time and became conditioned to environmental cues. In this case, the increased motor activity observed on the test day was qualitatively similar to the unconditioned response produced by AMPH.

Journal Article↗
PubMed2004

Isometric pull-push strengths in workspace: 2. Analysis of spatial factors.

The effect of reach levels, horizontal angles and vertical angles on isometric pull and push strengths of males and females in standing and seated positions was determined. The effect of reach levels on strength varied as a consequence of force direction, working position and gender. Reach level has a significant effect on women's pull strength in the seated position and on push strength in the standing position. The strength value was significantly greater in the extreme reach than in maximum or normal reach. Vertical angle phi had a significant effect on strength consistently in all cases. Strength values increased significantly with the increase of phi angles from 0 degrees to 45 degrees to 90 degrees. The horizontal angle theta had a significant influence only on the pull strength of standing and seated men and standing women (not seated woman). The maximum strength was significantly greater at theta = 90 degrees.

Adult↗
PubMedDate not supplied

Uncertainty and sensitivity analysis of spatial predictions of heavy metals in wheat.

Heavy metals seriously threaten the health of human beings when they enter the food chain. Therefore, policymakers require precise predictions of heavy metal concentrations in agricultural crops. In this paper we quantify the uncertainty of regression predictions of Cd and Pb in wheat (Triticum aestivum L.) and the contributions to the uncertainties in these predictions associated with inputs to the regression model. For each node of the 500- x 500-m grid covering the arable soils in The Netherlands, a latin hypercube sample size of 1000 is constructed from the uncertainty distributions of the explanatory variables (pH, soil organic matter [SOM], and heavy metal concentration in soil), the regression coefficients, and the random term of the regression model. This sample is used as input for the regression model to obtain 1000 values from the uncertainty distributions of the log(Cd) and log(Pb) concentration in wheat. There were no nodes where the recent EU quality standards for Cd and Pb (0.2 mg kg(-1) fresh wt.) in wheat were almost certain to be exceeded. For most nodes with clay soils, the quality standard for Cd in wheat almost certainly will not be exceeded; for Pb this is much less certain. The uncertainty in the Cd concentration in soil contributes most to the uncertainty in the predicted Cd concentrations in wheat (36% on the average), followed by the random term of the regression model (23%). For Pb the contribution of the random term is by far the largest (52%).

Agriculture↗
PubMed1998

Neural circuit analysis of spatial working memory: role of pre- and parasubiculum, medial and lateral entorhinal cortex.

Using a continuous recognition memory procedure for spatial location information, rats were given sequential presentation of individual arms on a 12-arm maze. Each arm contained a Froot Loop reinforcement the first time it was presented, and latency to traverse the arm was measured. A subset of the arms were repeated, but did not contain reinforcement. Repeated arms were presented with lags ranging from zero to six (from zero to six different arm presentations occurred between the first and repeated presentation). After completion of acquisition training (significantly longer latencies for repeated arms in comparison with the first presentation of an arm), rats received lesions of the medial or lateral entorhinal cortex, pre- and parasubiculum, or served as sham-operated controls. Based on continued postsurgery training and additional tests, the results indicated that rats with pre- and parasubiculum or pre- and parasubiculum plus medial entorhinal cortex produced sustained impairment in performing the task. Medial or lateral entorhinal cortex and control lesions did not display any sustained deficits. The data suggest that working memory for spatial location information is mediated primarily by the pre- and parasubiculum, but not medial entorhinal and lateral entorhinal cortex.

Animals↗
PubMedDate not supplied

Combined analysis of spatial and velocity displacement artifacts in phase contrast measurements of complex flows.

MR phase contrast (PC) velocity imaging is a promising tool for quantifying blood flow velocity in vivo. PC velocity imaging is, however, susceptible to artifacts that result from the displacement of spins during the finite duration pulse sequences. Such displacement artifacts can lead to errors in velocity measurements, especially in the presence of oblique and accelerating flows, which are common throughout the cardiovascular system. By tracking particles (representing spins) through a computed velocity field, and assuming that spatial and velocity encodings occur at discrete times during the pulse sequence, we simulate the separate and combined effects of oblique and acceleration artifacts on PC velocity images. We demonstrate, both by simulation and MR measurement, the errors associated with such artifacts in PC velocity measurements in a representative flow geometry. Using example particle trajectories, we provide a fluid dynamic basis for characteristic phase-velocity image distortions that can arise when imaging complex, physiologically relevant flows.

Animals↗
PubMed1998

Analysis of spatial distributions of cellular molecules during mechanical stressing of cell surface receptors using confocal microscopy.

Confocal laser scanning microscopy represents a suitable technique to study the localization of cellular components in three dimension. The authors used this technique to analyse cellular events related to mechanical stimulation of integrin receptors on the cell surface. By performing optical sections the distribution of integrin receptors on the apical surface of an osteoblastic cell was determined. Concerning intracellular compartimentalization of signal transduction events, it was demonstrated that mechanical stimulation of integrins induced their linkage to the cytoskeleton. Cytoskeletally associated proteins like vinculin and talin accumulated in the vicinity of the site where the mechanical stress was applied to integrins on the cell surface. Optical sections revealed that clustering of these proteins proceeded to the base of the cell with gradually decreasing extent. In summary, it was demonstrated that the local distribution of cellular components is an important factor in mechanically induced signal transduction.

Humans↗
PubMed1998

Model Analysis of Spatial Patterns in Mountain Pine Beetle Outbreaks.

The mountain pine beetle [MPB, Dendroctonus ponderosae Hopkins (Coleoptera: Scolytidae)] is an aggressive bark beetle, one that typically needs to kill host trees in order to successfully reproduce. This ecological adaptation has resulted in an organism that is both economically important and ecologically significant. Even though significant resources have been expended on MPB research, and a great deal of knowledge exists regarding individual aspects of MPB ecology, some of the most basic questions regarding outbreaks remain unanswered. In our opinion, one reason for the lack of synthesis and predictive power is the inadequate treatment of spatial dynamics in outbreak theories. This paper explicitly addresses the role of spatial dynamics in the precipitation and propagation of MPB outbreaks. We first describe a spatially dynamic model of the MPB/forest interaction that includes chemical ecology, spatial redistribution of beetles, attack, and resulting host mortality. The model is a system of 6 coupled, partial differential equations with 7 state variables and 20 parameters. It represents an attempt to capture the relatively complex predator/prey interaction between MPB and host trees by including the minimum phenomenological descriptions necessary for ecological credibility. This system of equations describes the temporal dynamics of: beetle attraction as a function of pheromone concentration; the change in numbers of flying and nesting beetles; tree resistance/susceptibility; and tree recovery from attack. Spatial dynamics are modeled by fluxes due to gradients in pheromones and kairomones, and the random redistribution of beetles in absence of semiochemicals. We then use the parameterized model to explore three issues central to the ecology of MPB/forest interaction. The first of these is in response to the need for objective ways to compare patterns of successful beetle attacks as they evolve in space. Simulation results indicate that at endemic levels, the pattern of successful attacks are determined almost exclusively by the underlying distribution of susceptible host trees (environmental determinism). As an outbreak develops, the pattern of successfully attacked trees switches to one that is dynamically driven by the self-generated semiochemical landscape (dynamic determinism). This switch from an environmentally determined spatial pattern to a dynamically driven pattern is the hallmark of an outbreak. We discuss the application of a spatial correlation coefficient that can be used to differentiate between the spatial distribution of killed trees in endemic and outbreak phases. The second issue we address through simulation is synchrony in adult emergence. Synchronous adult emergence is critical for the mass attack strategy necessary for overcoming tree defenses. Results from these simulations indicate that the degree of synchrony in adult emergence can have important consequences for assessing the risk of an outbreak. The final issue we investigate through simulation is the effect of spatial pattern of nurse trees (those successfully attacked the previous year) on outbreak potential. Simulations indicated that the spatial proximity of nurse trees was an important determinant of subsequent successful attacks. We conclude with a discussion of the general implications of our simulation experiments. Copyright 1998 Academic Press.

Journal Article↗
PubMed1992

Application of three-dimensional molecular hydrophobicity potential to the analysis of spatial organization of membrane protein domains. II. Optimization of hydrophobic contacts in transmembrane hairpin structures of Na+, K(+)-ATPase.

A method of packing of transmembrane hairpin helices in proteins is described. The procedure is based on the optimization of hydrophobic contacts calculated using the three-dimensional (3D) molecular hydrophobicity potential technique. To verify the validity of the computational scheme, we calculated relative orientations of membrane-spanning peptides in pairs L2-L3, M2-M3, and M4-M5 from L- and M-subunits of the photoreaction center of Rhodopseudomonas viridis and compared the predicted structures with those derived from atomic coordinates. The results of computer modeling agree with the X-ray data. We applied the approach proposed to study possible interhelical interactions in transmembrane hairpin structures of Na+, K(+)-ATPase.

Cell Membrane↗
PubMed1993

Application of three-dimensional molecular hydrophobicity potential to the analysis of spatial organization of membrane domains in proteins. III. Modeling of intramembrane moiety of Na+, K(+)-ATPase.

The most probable interlocation of transmembrane alpha-helices of Na+, K(+)-ATPase has been calculated by a computer-aided molecular simulation approach in the framework of models with eight and 10 helical peptides for the alpha-subunit. The method is based on the concept of three-dimensional molecular hydrophobicity potential (MHP) and provides valuable description of spatial hydrophobic properties of membrane-spanning segments as well as helix-helix packing interactions inside the membrane. Resulting model of the arrangement of intramembrane domain agrees with recent results on hydrophobic photolabeling of an intramembrane part of the beta-subunit and the sixth transmembrane segment of the alpha-subunit. It is also consistent with current ideas on hydrophobic organization of integral membrane proteins. Possible topology of a cation-binding site is discussed.

Cell Membrane↗
PubMed1994

XY chromosome behaviour in the germ-line of the human male: a FISH analysis of spatial orientation, chromatin condensation and pairing.

We have used multicolour fluorescence in situ hybridization to study the behaviour of the X and Y chromosomes in relation to a representative autosome, chromosome 1, on air-dried testicular preparations from normal fertile human males. In a proportion of Sertoli cells at interphase as well as spermatogonial metaphases there is an apparent selective undercondensation of the heterochromatic block of the long arm of the Y, which may be of functional significance with respect to Y-specific gene activity, initiating and maintaining spermatogenesis; we suggest that this may involve a mechanism similar to heterochromatin position-effect variegation in Drosophila. In the supporting Sertoli as well as pre-meiotic and leptotene cells the X and Y occupy relatively restricted domains at opposite poles of the nuclear membrane, while the chromosome 1 centromere regions are located interstitially and appear prealigned. The XY pairing and 'sex vesicle' formation comprises a complex series of spatial movement and differential condensation patterns. On the basis of these observations we propose that: the XIST/Xist gene, known to be involved in somatic X inactivation, imposes a chromatin reorganization leading to bending at the X-inactivation centre both at first meiotic prophase in males and in the soma in females; and the differential X and Y segments are protected from potentially deleterious meiotic exchanges by their separate spatial orientation. In addition, there is an indication that the timing of pairing and first meiotic segregation of the sex chromosomes is different, and precocious in comparison to the pairing and segregation of the autosomes, which may explain the high incidence of sex chromosome aneuploidy in sperm.

Animals↗
PubMed2003

Single motor unit analysis from spatially filtered surface electromyogram signals. Part I: spatial selectivity.

The aim of the study was to compare experimentally, on the basis of single motor unit (MU) activities, the selectivity of different spatial filters commonly used to detect surface electromyogram (EMG) signals. Surface EMG signals were recorded from the biceps brachii and the upper trapezius muscle of five subjects using a two-dimensional (2D) electrode array consisting of 16 pin electrodes. The subjects performed isometric contractions at different elbow angles and shoulder abduction and flexion. The same monopolar surface EMG signals were filtered using longitudinal single and double differential, transverse single and double differential and normal double differential filters. From the single MU action potentials, extracted by automatic EMG decomposition, indexes of transverse (perpendicular with respect to the fibre direction) and longitudinal (along the fibre direction) selectivity were computed. The number of detected MUs was 46 for the upper trapezius, with the arms held in the sagittal plane, and 52 when the arms were held in the frontal plane; 85 MUs were identified from the biceps brachii contractions. The results showed that transverse selectivity was significantly higher for the 2D and transverse one-dimensional (1D) filters with respect to the 1D longitudinal filters, whereas longitudinal selectivity was higher (i.e. MU action potentials were shorter) for the 2D filter and the longitudinal double differential filter. In particular, the relative attenuation of potential amplitude moving 5 mm from the source was, on average (for the two muscles), 16.5% for the least selective filter in the transverse direction (longitudinal single differential) and 35.7% for the most selective one in the same direction (transverse double differential). The MU action potential duration was, on average, 13.8 ms for the most selective filter in the longitudinal direction (longitudinal double differential) and 18.7 ms for the least selective one (transverse double differential). The normal double differential filter resulted in spatial selectivity indexes that ware not statistically different in the two directions from those of the best filters in each direction.

Action Potentials↗
PubMed2003

Single motor unit analysis from spatially filtered surface electromyogram signals. Part 2: conduction velocity estimation.

The aim of the study was to compare experimentally conduction velocity (CV) estimates obtained with different estimation methods based on surface electromyogram (EMG) signals detected using five spatial filters. The filters investigated were the longitudinal single and double differential, transverse single and double differential, and normal double differential. The same surface EMG signals detected as described in Part 1 were used in this work. CV was estimated with four commonly used delay estimation techniques, i.e. from the distance between the peak values of two waveforms (with and without polynomial interpolation around the peak), and by the maximum likelihood estimate (MLE) based on two or more surface EMG channels. The average standard deviation of CV estimation (for all the MUs and the two muscles together) was 0.61 m s(-1) and 0.79 m s(-1) for the peak method, with and without interpolation, respectively, and 0.50 m s(-1) and 0.31 m s(-1) for the MLE method, from two and more surface EMG channels, respectively. Moreover, the mean of CV estimates varied by as much as 1 m s(-1) depending on the spatial filter used and the method adopted for CV estimation. Considering the dependence on the spatial filter only, the average (over all estimation methods) CV estimates obtained with the five spatial filters were 4.32 m s(-1) (normal double differential), 4.23 m s(-1) (longitudinal double differential), 4.61 m s(-1) (transverse double differential), 4.64 m s(-1) (transverse single differential) and 4.03 m s(-1) (longitudinal single differential). It was concluded that the comparison of single MU CV values obtained in different studies is critical if different spatial filters and processing techniques are used for their estimation. Higher estimates of CV were attributed to a smaller reduction in non-travelling signal components and thus were assumed to be positively biased.

Action Potentials↗
PubMed2005

Human archival tissues provide a valuable source for the analysis of spatial genome organization.

Sections from archival formalin-fixed, paraffin wax-embedded human tissues are a valuable source for the study of the nuclear architecture of specific tissue types in terms of the three-dimensional spatial positioning and architecture of chromosome territories and sub-chromosomal domains. Chromosome painting, centromeric, and locus-specific probes were hybridized to tissue microarrays prepared from formalin-fixed paraffin wax-embedded samples of pancreas and breast. The cell nuclei were analyzed using quantitative three-dimensional image microscopy. The results obtained from non-neoplastic pancreatic cells of randomly selected individuals indicated that the radial arrangement of the chromosome 8 territories as well as their shape (roundness) did not significantly differ between the individuals and were in accordance with assumptions of a probabilistic model for computer simulations. There were considerable differences between pancreatic tumor and non-neoplastic cells. In non-neoplastic ductal epithelium of the breast there was a larger, but insignificant, variability in the three-dimensional positioning of the centromere 17 and HER2 domains between individuals. In neoplastic epithelial breast cells, however, the distances between centromere and gene domains were, on average, smaller than in non-neoplastic cells. In conclusion, our results demonstrate the feasibility of studying the genome architecture in archival, formalin-fixed, paraffin wax-embedded human tissues, opening new directions in tumor research and cell classification.

Breast↗