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The effects of voluntary lateral orienting on positive manifold for lateralized cognitive tasks.

As an extension of previous studies (Urbanczyk, Angel, & Kennelly, Brain and Cognition, 8, 206-226) examining the effects of unimanual tapping on lateralized cognitive tasks, lateral body orienting was added to an established dual task paradigm to generate differential hemispheric activation and shifts of attention. One hundred twenty right-handed university students retained sequences of digits or spatial locations for 20 sec either alone or during finger tapping. By turning head and eyes left or right, the hemisphere congruent with the sequences (LH for digits, RH for locations) or incongruent (vice versa) was activated. Activation had little effect on retention means but greatly affected resource composition, supporting task performance. Congruent orientation produced significantly higher positive correlations between digit and location tasks than incongruent orientation. Females showed higher sequence retention correlations than males across both orienting groups. For females, congruent activation enhanced tapping rates and tapping-retention task correlations. For males, activation affected neither of these. These results suggest that congruent attentional orienting may couple or integrate regions of the less activated hemisphere into networks of the more activated hemisphere. Greater inter- and intrahemispheric connectivity in the female cortex may produce a greater dependence upon a general attentional "resource."

Adult↗

The P5 protein from bacteriophage phi-6 is a distant homolog of lytic transglycosylases.

Peptidases are classical objects of enzymology and structural studies. However, a few protein families with experimentally characterized proteolytic activity, but unknown catalytic mechanism and three-dimensional structures, still exist. Using comparative sequence analysis, we deduce spatial structure for one of such families, namely, U40, which contains just one P5 protein from bacteriophage phi-6. We show that this singleton sequence possesses conserved sequence motifs characteristic of lysozymes and is a distant homolog of lytic transglycosylases that cleave bacterial peptidoglycan. The structure of the P5 protein is therefore predicted to adopt the lysozyme-like fold shared by T4, lambda, C-type, G-type lysozymes, and lytic transglycosylases. Since previous biochemical experiments with P5 of phi-6 have indicated that the purified enzyme possesses endopeptidase activity and not glycosidase activity, our results point to the possibility of a newly evolved molecular function and call for further experimental characterization of this unusual P5 protein.

Amino Acid Sequence↗

Assessing surveillance using sensitivity, specificity and timeliness.

Monitoring ongoing processes of illness to detect sudden changes is an important aspect of practical epidemiology and medicine more generally. Most commonly, the monitoring has been restricted to a unidimensional stream of data over time. In such situations, analytic results from the industrial process monitoring have suggested optimal approaches to monitor the data streams. Data streams including spatial location as well as temporal sequence are becoming available. Monitoring methods that incorporate spatial data may prove superior to those that ignore it. However, analytically, optimal methods for spatial surveillance data may not exist. In the present article, we introduce and discuss evaluation metrics that can be used to compare the performance of statistical methods of surveillance. Our general approach is to generalize receiver operating characteristic (ROC) curves to incorporate the time of detection in addition to the usual test characteristics of sensitivity and specificity. In addition to weighting ordinary ROC curves by two measures of timeliness, we describe three three-dimensional generalizations of ROC curves that result in timeliness-ROC surfaces. Working in the context of surveillance of cases of disease to detect a sudden outbreak, we demonstrate these in an artificial example and in a previously described simulation context and show how the metrics differ. We also discuss the differences and under which circumstances one might prefer a given method.

Anthrax↗

[Evaluation of PROPELLER MR imaging: preliminary experiences].

Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction (PROPELLER) MR imaging (MRI) has a unique ability to correct motion artifacts and is expected to be useful in diffusion-weighted MRI. This article describes preliminary experiences with PROPELLER MRI. PROPELLER uses a radial scan variation of the fast spin-echo sequence and it shows much less spatial deterioration than the echo-planar imaging sequence. To determine the optimal parameters of this technique, we calculated the signal intensities of phantoms and brains in various settings. PROPELLER MR examinations were also performed in 66 patients for clinical use. PROPELLER MRI appears to be a promising and useful technique.

Artifacts↗

Longitudinal stability of MRI for mapping brain change using tensor-based morphometry.

Measures of brain change can be computed from sequential MRI scans, providing valuable information on disease progression, e.g., for patient monitoring and drug trials. Tensor-based morphometry (TBM) creates maps of these brain changes, visualizing the 3D profile and rates of tissue growth or atrophy, but its sensitivity depends on the contrast and geometric stability of the images. As part of the Alzheimer's Disease Neuroimaging Initiative (ADNI), 17 normal elderly subjects were scanned twice (at a 2-week interval) with several 3D 1.5 T MRI pulse sequences: high and low flip angle SPGR/FLASH (from which Synthetic T1 images were generated), MP-RAGE, IR-SPGR (N = 10) and MEDIC (N = 7) scans. For each subject and scan type, a 3D deformation map aligned baseline and follow-up scans, computed with a nonlinear, inverse-consistent elastic registration algorithm. Voxelwise statistics, in ICBM stereotaxic space, visualized the profile of mean absolute change and its cross-subject variance; these maps were then compared using permutation testing. Image stability depended on: (1) the pulse sequence; (2) the transmit/receive coil type (birdcage versus phased array); (3) spatial distortion corrections (using MEDIC sequence information); (4) B1-field intensity inhomogeneity correction (using N3). SPGR/FLASH images acquired using a birdcage coil had least overall deviation. N3 correction reduced coil type and pulse sequence differences and improved scan reproducibility, except for Synthetic T1 images (which were intrinsically corrected for B1-inhomogeneity). No strong evidence favored B0 correction. Although SPGR/FLASH images showed least deviation here, pulse sequence selection for the ADNI project was based on multiple additional image analyses, to be reported elsewhere.

Aged↗

Functional MRI of the motor cortex using a conventional gradient system: comparison of FLASH and EPI techniques.

Gradient echo (GE) and echo planar imaging (EPI) techniques are two different approaches to functional MRI (fMRI). In contrast to GE sequences, the ultra short EPI technique facilitates fMRI experiments with high spatial and temporal resolution or mapping of the whole brain. Although it has become the method of choice for fMRI, EPI is generally restricted to modern scanners with a strong gradient system. The aim of our study was to evaluate the applicability of EPI for fMRI of the motor cortex using a 1.5 T scanner with a conventional gradient system of 10 mT/m (rise time: 1 ms). Therefore, EPI was compared with a well-established high-resolution fast low-angle shot (FLASH) technique (matrix size 1282). The FLASH technique was applied additionally with a 64(2) matrix size to exclude influences caused by different spatial resolution, because the EPI sequence was restricted to a 64(2) matrix size. A total of 35 healthy volunteers were included in this study. The task consisted of clenching and spreading of the right hand. FLASH and EPI techniques were compared regarding geometric distortions as well as qualitative and quantitative fMRI criteria: Mean signal increase between activation and rest and the area of activation were measured within the contralateral, ipsilateral, and supplementary motor cortex. The quality of subtraction images between activation and rest, as well as the quality of z-maps and time course within activated regions of interest, was evaluated visually. EPI revealed significant distortions of the anterior and posterior brain margins; lateral distortions (relevant for the motor cortex) could be neglected in most cases. The mean signal increase was significantly higher using FLASH 1282 compared to FLASH 64(2) and EPI 64(2), whereas the activated areas proved to be smaller in FLASH 1282 functional images. Both results can be explained by well-documented partial volume effects, caused by different voxel size. Similar quality of the subtraction images and of the time courses in different regions of interest were found for all techniques under investigation, but slightly reduced quality of z-map in FLASH 1282. Within the limits of reproducibility and measurement accuracy, the location of contralateral activation was similar using FLASH and EPI sequences. In conclusion, EPI proved to be a reliable technique for fMRI of the motor cortex, even on an MR scanner with a conventional gradient system.

Adult↗

GenEST, a powerful bidirectional link between cDNA sequence data and gene expression profiles generated by cDNA-AFLP.

The release of vast quantities of DNA sequence data by large-scale genome and expressed sequence tag (EST) projects underlines the necessity for the development of efficient and inexpensive ways to link sequence databases with temporal and spatial expression profiles. Here we demonstrate the power of linking cDNA sequence data (including EST sequences) with transcript profiles revealed by cDNA-AFLP, a highly reproducible differential display method based on restriction enzyme digests and selective amplification under high stringency conditions. We have developed a computer program (GenEST) that predicts the sizes of virtual transcript-derived fragments (TDFs) of in silico-digested cDNA sequences retrieved from databases. The vast majority of the resulting virtual TDFs could be traced back among the thousands of TDFs displayed on cDNA-AFLP gels. Sequencing of the corresponding bands excised from cDNA-AFLP gels revealed no inconsistencies. As a consequence, cDNA sequence databases can be screened very efficiently to identify genes with relevant expression profiles. The other way round, it is possible to switch from cDNA-AFLP gels to sequences in the databases. Using the restriction enzyme recognition sites, the primer extensions and the estimated TDF size as identifiers, the DNA sequence(s) corresponding to a TDF with an interesting expression pattern can be identified. In this paper we show examples in both directions by analyzing the plant parasitic nematode Globodera rostochiensis. Various novel pathogenicity factors were identified by combining ESTs from the infective stage juveniles with expression profiles of approximately 4000 genes in five developmental stages produced by cDNA-AFLP.

Animals↗

Sequence parameters of double spin-echo sequences affect quantification of citrate.

Quantification of citrate by localized 1H spectroscopy is usually performed using the water signal as reference, but the signal behavior of the J-coupled AB spin system of citrate after multipulse excitation is not as trivial as for uncoupled substances. The influence of the timing scheme of double spin-echo sequences and of the spatial flip angle distribution of (nonideal) refocusing pulses was analyzed systematically for the citrate resonances. Both single echo times of the double spin-echo sequence were varied between 20 ms and 250 ms in theoretical and experimental approaches. Relatively long total echo times (TE > 120 ms) provide high selectivity to citrate signals, since signals from triglycerides at 2.6 ppm are markedly reduced. Asymmetrical timing schemes of the double spin-echo sequence with one short single echo time of 20 ms and one longer single echo time of about 120 ms result in high integral signal from the central lines of citrate, whereas symmetrical timing leads to high sensitivity for total echo times TE near 100 ms. The integral citrate signals in spectra with relatively long echo times (TE > 120 ms) were found to depend markedly on the type of the refocusing pulses, affecting quantitative citrate measurements in vitro and in vivo.

Citric Acid↗

[High resolution contrast-enhanced 3D MR-angiography of renal arteries using parallel imaging (SENSE)].

PURPOSE: To compare three dimensional contrast enhanced MR angiography with parallel imaging technique (sensitivity encoding) to standard MR angiography technique. MATERIAL AND METHODS: CE-3D MRA of renal arteries was performed in 22 patients (23 examinations) on a 1.5 T MR- scanner (Gyroscan Intera, Philips, Netherlands). For contrast enhanced MRA a single dose of Gd-DTPA (0.1 mmol/kg b.w.) was administered. Group I: The following standard 3D gradient echo (GE) sequence was performed in 9 of the 22 patients: TR: 4.3 ms, TE: 1.5 ms, flip angle: 40, 40 slices, scan duration: 19 seconds. A spatial resolution of 1.96 x 1.76 x 3.0 mm (3) (1.76 x 1.76 x 1.5 mm (3) interpolated) was obtained. Group II: 14 examinations were acquired in 13 patients: TR, TE and flip angle were equal compared to the first protocol. The k-space lines were acquired with CENTRA (contrast-enhanced time robust angiography) and parallel imaging technique (SENSE). 60 slices were acquired, scan duration was 24 seconds. The spatial resolution of this sequence was 1.19 x 1.08 x 2.0 mm (3) (0,84 x 0,84 x 1,0 mm (3) interpolated). Original images and calculated maximum intensity projection (MIP) images were analysed by two radiologists. Image quality and the visibility of renal arteries were rated on a four-point scale. RESULTS: In the first group the image quality was rated "good" in 8/9 patients. The renal arteries were detected in all cases and rated "good". The anterior and posterior segments were rated "good" in only 5/9 and the lobar arteries were detectable only in 3 of 9 cases. The interlobar arteries could not be seen in these patients. In the second group the image quality was rated excellent in 5 examinations and good in 9 of 14 examinations. The rating for the renal arteries was excellent in all examinations (14/14). The results of the anterior and posterior segment were as followed: excellent 5/14, good 7/14, insufficient 2/14; the lobar arteries: good 6/14, insufficient 6/14 and not detectable 2/14. Interlobar arteries could be seen in 7/14 examinations, but the quality was insufficient. In 7/14 the interlobar arteries could not be detected. CONCLUSION: The use of parallel imaging technique improves image quality and the delineation of small vessels in renal MRA.

Aneurysm↗

High-resolution computational models of genome binding events.

Direct physical information that describes where transcription factors, nucleosomes, modified histones, RNA polymerase II and other key proteins interact with the genome provides an invaluable mechanistic foundation for understanding complex programs of gene regulation. We present a method, joint binding deconvolution (JBD), which uses additional easily obtainable experimental data about chromatin immunoprecipitation (ChIP) to improve the spatial resolution of the transcription factor binding locations inferred from ChIP followed by DNA microarray hybridization (ChIP-Chip) data. Based on this probabilistic model of binding data, we further pursue improved spatial resolution by using sequence information. We produce positional priors that link ChIP-Chip data to sequence data by guiding motif discovery to inferred protein-DNA binding sites. We present results on the yeast transcription factors Gcn4 and Mig2 to demonstrate JBD's spatial resolution capabilities and show that positional priors allow computational discovery of the Mig2 motif when a standard approach fails.

Base Sequence↗

Affine structure from motion.

A mobile observer samples sequences of narrow-field projections of configurations in ambient space. The so-called structure-from-motion problem is to infer the structure of these spatial configurations from the sequence of projections. For rigid transformations, a unique metrical reconstruction is known to be possible from three orthographic views of four points. However, human observers seem able to obtain much shape information from a mere pair of views, as is evident in the case of binocular stereo. Moreover, human observers seem to find little use for the information provided by additional views, even though some improvement certainly occurs. The rigidity requirement in its strict form is also relaxed. We indicate how solutions of the structure-from-motion problem can be stratified in such a way that one explicitly knows at which stages various a priori assumptions enter and specific geometrical expertise is required. An affine stage is identified at which only smooth deformation is assumed (thus no rigidity constraint is involved) and no metrical concepts are required. This stage allows one to find the spatial configuration (modulo an affinity) from two views. The addition of metrical methods allows one to find shape from two views, modulo a relief transformation (depth scaling and shear). The addition of a third view then merely serves to settle the calibration. Results of a numerical experiment are discussed.

Form Perception↗

[Quadri-dimensional analysis of the electroencephalography. First application to an episode of paradoxical sleep in man].

A first example of quadri-dimensional EEG analysis is presented which is characteristic of a series of ten analyses episodes of paradoxical sleep recorded in polygraphy during 5 nights' sleep in three human volunteers. A first EEG recording of wakefulness, eyes open, with visual fixation of a central point, was followed by a polygraphic night of sleep recording after habituation. The first subject was recorded during three nights; two other subjects during one night only after habituation. An EEG montage of 16 channels was quantified by spectral analysis and parametrization, after artefact rejection, for the reference sequence of wakefulness and further episodes of paradoxical sleep. After temporal and spatial interpolation algorithms, for each sequence, a series of root-mean-square successive EEG maps were computed and displayed, between 0.5 to 30 Hz. Low amplitude values of locally activated areas were chosen during the wakefulness EEG sequence and provided filtering thresholds for isolating activated areas during paradoxical sleep. The first 30 maps of each episode were piled up one on top of the other, along a vertical time axis, then dynamically visualised in colors and 3D. The "trajectories of activated areas" were then displayed in a quadri-dimensional functional space (x-y: spatial map of the scalp; t: time; color or black and white: filtered or unfiltered rms EEG amplitudes). The EEG trajectories of awakened areas, appeared through time like unique "fibres" or double fibres after bifurcation. The unique fibres were located over left temporo-central activated areas and a double fibre appeared after bifurcation over the right parietal area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Conserved spatially interacting motifs of protein superfamilies: application to fold recognition and function annotation of genome data.

Limitations in techniques for the elucidation of protein function have led to an increasing gap between the annotated proteins and those encoded in a genome. The functional selection and three-dimensional structural constraints of proteins in nature often relate to the retention of significant sequence similarity between proteins of similar fold and function despite poor sequence identity. We identify spatially interacting conserved regions, or motifs, within protein superfamilies that are critical for structure and/or function. A search in sequence databases using these descriptors as additional constraints is an approach to identifying putative additional members of superfamilies. Such constrained searches have been tested against proteins of known structure to demonstrate high percentage specificity (93) with a low error rate of 0.0004. This approach has been compared with other sensitive sequence search methods (e.g., PSI-BLAST, HMMsearch, and IMPALA). It has been extended to analyze the distribution of 11 superfamilies in 93 genomes, including the human genome.

Amino Acid Motifs↗

High intron sequence conservation across three mammalian orders suggests functional constraints.

Several studies have demonstrated high levels of sequence conservation in noncoding DNA compared between two species (e.g., human and mouse), and interpreted this conservation as evidence for functional constraints. If this interpretation is correct, it suggests the existence of a hidden class of abundant regulatory elements. However, much of the noncoding sequence conserved between two species may result from chance or from small-scale heterogeneity in mutation rates. Stronger inferences are expected from sequence comparisons using more than two taxa, and by testing for spatial patterns of conservation in addition to primary sequence similarity. We used a Bayesian local alignment method to compare approximately 10 kb of intron sequence from nine genes in a pairwise manner between human, whale, and seal to test whether the degree and pattern of conservation is consistent with neutral divergence. Comparison of the three sets of conserved gapless pairwise blocks revealed the following patterns: The proportion of identical intron nucleotides averaged 47% in pairwise comparisons and 28% across the three taxa. Proportions of conserved sequence were similar in unique sequence and general mammalian repetitive elements. We simulated sequence evolution under a neutral model using published estimates of substitution rate heterogeneity for noncoding DNA and found pairwise identity at 33% and three-taxon identity at 16% of nucleotide sites. Spatial patterns of primary sequence conservation were also nonrandomly distributed within introns. Overall, segments of intron sequence closer to flanking exons were significantly more conserved than interior intron sequence. This level of intron sequence conservation is above that expected by chance and strongly suggests that intron sequences are playing a larger functional role in gene regulation than previously realized.

Animals↗

Intravascular signal in MR imaging: use of phase display for differentiation of blood-flow signal from intraluminal disease.

Intravascular signal from flowing blood is frequently observed on magnetic resonance (MR) images and may be indistinguishable from partial or complete vascular occlusion caused by thrombus or tumor. With a phase-display reconstruction method, qualitative assessment of large-vessel patency within the abdomen was undertaken in 15 healthy subjects and 12 patients with angiographically or surgically documented intravascular thrombus or tumor. Computed tomographic (CT) scans were available in all patients for correlation. MR studies were performed with a multisection spin-echo pulse sequence and two-dimensional Fourier transform spatial encoding. Data acquired from a single sequence was reconstituted in two ways to provide both routine anatomic images and a pictorial representation of large-vessel flow on a phase-sensitive image. With this method, reliable and easy differentiation of intraluminal thrombus and tumor from blood flow signal within large vessels was achieved. Information from these phase-display images compared favorably with findings from angiography and contrast-enhanced CT in the determination of luminal patency and obstruction.

Blood Circulation↗

Anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact canine heart.

The effects of the activation sequence on ventricular repolarization and its spatial gradient were examined in anesthetized open-chest dogs. Unipolar and bipolar electrograms were recorded from 47 epicardial sites on the anterior left ventricular wall using a mapping electrode. The local QT interval (QT) and the activation time (AT) at each site were measured on the unipolar and bipolar electrograms, respectively. The QT index (QTI) was defined as the QT minus AT interval, and was used as a measure of local repolarization. QTI was longer at each site during propagation that was longitudinal (L) (219+/-21 ms) than during propagation transverse (T) (202+/-22 ms, p<0.001) to the epicardial fiber orientation or during atrial pacing (165+/-20 ms, p<0.001). During L-propagation, the QTI shortened as a function of the distance from the stimulus. The spatial gradient was steeper during T-propagation (p<0.05). Monophasic action potentials (MAP) were also recorded simultaneously at 4 epicardial sites. The MAP duration during ventricular pacing was longer than during atrial pacing at sites within 1.5 cm of the pacing site. This difference disappeared at more distant sites and was attenuated by a simultaneous stimulus from a site symmetrically aligned along the fiber. These findings indicate that anisotropic conduction prolongs ventricular repolarization and increases its spatial gradient in the intact heart. An electrotonic downstream effect appears to be the cause.

Animals↗

Poisson process approximation for sequence repeats, and sequencing by hybridization.

Sequencing by hybridization is a tool to determine a DNA sequence from the unordered list of all l-tuples contained in this sequence; typical numbers for l are l = 8, 10, 12. For theoretical purposes we assume that the multiset of all l-tuples is known. This multiset determines the DNA sequence uniquely if none of the so-called Ukkonen transformations are possible. These transformations require repeats of (l-1)-tuples in the sequence, with these repeats occurring in certain spatial patterns. We model DNA as an i.i.d. sequence. We first prove Poisson process approximations for the process of indicators of all leftmost long repeats allowing self-overlap and for the process of indicators of all left-most long repeats without self-overlap. Using the Chen-Stein method, we get bounds on the error of these approximations. As a corollary, we approximate the distribution of longest repeats. In the second step we analyze the spatial patterns of the repeats. Finally we combine these two steps to prove an approximation for the probability that a random sequence is uniquely recoverable from its list of l-tuples. For all our results we give some numerical examples including error bounds.

Algorithms↗

Strong spatial genetic structure in peripheral but not core populations of Sitka spruce [Picea sitchensis (Bong.) Carr.].

We examined spatial genetic structure within eight populations of Sitka spruce classified as core or peripheral based on ecological niche, and continuous or disjunct based on species distribution. In each population, 200 trees were spatially mapped and genotyped for eight cDNA-based sequence tagged site (STS) codominant markers. Spatial autocorrelation was assessed by estimating p(ij), the average co-ancestry coefficient, between individuals within distance intervals. The distribution of alleles and genotypes within core populations was almost random, with nonsignificant co-ancestry values among trees as close as 50 m in core populations. In contrast, the distribution of alleles and genotypes within peripheral populations revealed an aggregation of similar multilocus genotypes, with co-ancestry values greater than 0.20 among trees up to 50 m apart and significant, positive values between trees up to 500 m. The relatively high density of reproductive adults in core populations may lead to highly overlapping seed shadows that limit development of spatial genetic structure. However, in peripheral populations with a lower density of adults, the distribution of alleles and genotypes was highly structured, likely due to offspring establishment near maternal trees and subsequent biparental inbreeding, as well as more recent population establishment at the leading edge of post-Pleistocene range expansion. Conserving genetic diversity in peripheral populations may require larger reserves for in situ conservation than required in core populations. These data on spatial genetic structure can be used to provide guidance for sampling strategies for both ex situ conservation and research collections.

British Columbia↗