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A new method for incorporating weighted temporal and spatial smoothing in the inverse problem of electrocardiography.

In this paper, we present a method for incorporating temporal smoothing (TS) into the estimate of epicardial potentials from body surface potential data. Our algorithm employs a different spatial smoothing parameter, chosen by the composite residual error and smoothing operator criteria, at each time step in the sequence. The total spatial smoothing term is then simply partitioned between temporal and spatial smoothing. The algorithm appears to be quite robust with regard to this partitioning. The new method was evaluated in the setting of additive Gaussian noise, but otherwise realistic conditions of body geometry and reference epicardial potentials. In examining the match between estimated and measured electrograms, or the match between estimated isopotential maps and measured isopotential maps, the estimates constructed using the new TS algorithm produced consistently smaller relative errors than those constructed using a quasi-static (QS) algorithm or those constructed by postprocessing the QS estimate with a moving average filter.

Algorithms↗

RST: a connectionist architecture to deal with spatiotemporal relationships.

In the past decade, connectionism has proved its efficiency in the field of static pattern recognition. The next challenge is to deal with spatiotemporal problems. This article presents a new connectionist architecture, RST (réseau spatio temporel [spatio temporal network]), with such spatiotemporal capacities. It aims at taking into account at the architecture level both spatial relationships (e.g., as between neighboring pixels in an image) and temporal relationships (e.g., as between consecutive images in a video sequence). Concerning the spatial aspect, the network is embedded in actual space (two) or three-dimensional-, the metrics of which directly influence its structure through a connection distribution function. For the temporal aspect, we looked toward biology and used a leaky-integrator neuron model with a refractory period and postsynaptic potentials. The propagation of activity by spatiotemporal synchronized waves enables RST to perform motion detection and localization in sequences of video images.

Image Processing, Computer-Assisted↗

Neurogenic hypertension. A new MRI protocol for the evaluation of neurovascular compression of the cranial nerves IX and X root-entry zone.

OBJECTIVE: Neurovascular compression of the rostral ventrolateral medulla (RVLM) has been implicated in the pathogenesis of essential hypertension. Although MRI has been widely used to evaluate the morphologic relation of structures in this region, spatial resolution of the previously used techniques was limited. This article describes the use of a new MRI protocol that combines two sequences with improved spatial resolution and complementary image information as well as a set of defined criteria for image analysis. METHODS: MRI of the brain stem was performed in 60 hypertensive and 50 normotensive subjects using a 3D-CISS and a 3D-FISP-MRA sequence. Neurovascular contact in the RVLM was independently assessed by four readers using predefined criteria and compared with a consensus finding. Agreement was expressed by kappa statistics on a 0 to 1 scale. RESULTS: Left-sided neurovascular contact within the RVLM was found in 13 (22%) hypertensive and 6 (12%) control subjects. The inter-reader agreement for positive and negative findings ranged from 0.47 to 0.79; agreement to the consensus finding ranged from 0.65 to 0.90. CONCLUSIONS: The combination of 3D-CISS and arterial flow-sensitive 3D-FISP, together with the evaluation criteria defined in this study, can be used for describing the finer anatomic features of the brain stem, and in particular for investigation of neurovascular contact of the IX/X cranial nerve root-entry zone. The high quality of images and the substantial or almost perfect reader-consensus agreement should make this protocol useful for future investigations of the neurovascular compression syndrome in patients with essential hypertension and possibly in other neurovascular compression syndromes, such as trigeminal neuralgia and hemifacial spasm.

Adult↗

Sequences required for transcriptional initiation of the Saccharomyces cerevisiae CYC7 genes.

A series of BAL 31 deletions were constructed in the upstream region of the Saccharomyces cerevisiae CYC7 gene to determine sequences required for transcriptional initiation. These deletions identified the TATA box as an alternating A-T sequence at -160 and the initiation sequences as well as the spatial relationship between them. The TATA box was necessary for wild-type levels of expression of the CYC7 gene. Decreasing the distance between the TATA sequence and the initiation site did not alter gene expression, but the site of transcription was shifted 3'-ward. In most cases, transcription initiated at a number of sites, the 5'-most of which was the first suitable site greater than 45 base pairs 3' of the TATA sequence, suggesting a spatial relationship between these sequences. Consensus sequences previously proposed for initiation sites were evaluated with respect to the start sites identified in this study as well as the start sites of other yeast genes.

Base Sequence↗

Hydrogen ultrathin phase-encoded spectroscopy (HUPSPEC).

This paper describes a new clinical spectroscopy pulse program, hydrogen ultrathin phase-encoded spectroscopy. This sequence combines high spatial resolution with magnitude hydrogen spectroscopy. A linear volume is spatially frequency encoded with a conventional readout gradient and phase encoded spectrally by incrementing the timing of acquisition. The pulse sequence is implemented on a whole-body MRI scanner and supports several standard scanner options, including autoprescanning, offset of the center of field of view in the frequency-encoding direction, and oblique imaging. Some preliminary experimental experience is reported, demonstrating the possibility of observing the spectral linewidths of fat and water in marrow, and of observing the spectral linewidths of fat and water in marrow, and of observing multiline spectra. Combination of the technique with water suppression methods in a sequence called WASHUP is also discussed.

Adult↗

Spatial distribution of GC- and AT-rich DNA sequences within human chromosome territories.

Previous topological analyses of DNA sequence organization in the interphase chromosome mainly focused on the spatial distribution of individual gene copies within chromosome territories. In order to achieve a more comprehensive view into the subchromosomal arrangement of DNA, we isolated the GC-richest/gene-richest fraction (H3 isochores) as well as AT-richest/gene-poorest fraction of human genomic DNA (L1+L2 isochores) and visualized the respective DNA within individual chromosome territories by means of dual-color FISH. Application of confocal laser scanning microscopy and dedicated 3D image analysis software, which differentiated territory subvolumes by peeling shells one voxel in width, revealed a significant difference in the intraterritorial distribution of these two DNA sequence classes. While the H3 isochores were found localized in all subvolumes of the territories at similar frequency, simultaneously detected L1+L2 isochores were observed more to the interior of the same chromosome territories. Thus the GC-rich sequences display a much higher variability in their intraterritorial localization than AT-rich DNA fragments.

Chromosomes, Human↗

p57Kip2 (cdkn1c): sequence, splice variants and unique temporal and spatial expression pattern in the rat pancreas.

The cyclin-dependent kinase (CDK) inhibitor p57Kip2 (CDKN1C) is a negative regulator of cell proliferation, binding to a variety of cyclin-CDK complexes and inhibiting their kinase activities in vitro. The p57Kip2 gene is imprinted and the maternal allele is expressed in terminally differentiated cells, including human beta-cells. Somatic loss of p57Kip2 expression is associated with increased beta-cell proliferation in the focal form of Hyperinsulinism of Infancy. We cloned and sequenced the rat ortholog of p57Kip2, and demonstrate that it is highly homologous to the mouse gene. However, the human and rodent genes are quite divergent. Despite having highly homologous C- and N-terminal domains, the mid-portion of the human gene is entirely different from that of its rodent counterparts. Expression of p57Kip2 was evaluated during fetal and postnatal development, and a highly cell-specific, temporal and spatial expression profile was found. In contrast to other tissues, the expression pattern in rat pancreas was entirely opposite from that previously reported in man, with high levels of expression in rodent exocrine cells, but no expression in beta-cells during any stage of development. These findings demonstrate that p57Kip2 expression is highly regulated. In the pancreas, the functional significance of this gene appears to be quite different in humans when compared with rodents, suggesting that a better understanding of the function of this protein may provide new insights into the mechanisms involved in the control of human beta-cell mass.

Alternative Splicing↗

Method revealing latent periodicity of the nucleotide sequences modified for a case of small samples.

An earlier reported method for revealing latent periodicity of the nucleotide sequences has been considerably modified in a case of small samples, by applying a Monte Carlo method. This improved method has been used to search for the latent periodicity of some nucleotide sequences of the EMBL data bank. The existence of the nucleotide sequences' latent periodicity has been shown for some genes. The results obtained have implied that periodicity of gene structure is projected onto the periodicity of primary amino acid sequences and, further, onto spatial protein conformation. Even though the periodic structure of gene sequences has been eroded, it is still retained in primary and/or spatial structures of corresponding proteins. Furthermore, in a few cases the study of genes' periodicity has suggested their possible evolutionary origin by multifold duplications of some gene's fragments.

Base Sequence↗

Sequence variation of the ribosomal DNA second internal transcribed spacer region in two spatially-distinct populations of Amblyomma americanum (L.) (Acari: Ixodidae).

Sequence analysis of the ribosomal DNA second internal transcribed spacer (ITS 2) region in 2 spatially distinct populations of Amblyomma americanum (L.) revealed intraspecific variation. Nucleotide sequences from multiple DNA extractions and several polymerase chain reaction amplifications of eggs from mixed-parentage samples from both populations of ticks revealed that 12 of 1,145 (1.0%) sites varied. Three of the 12 sites of variation were distinct between the 2 A. americanum populations, which corresponded to a rate of 0.26%. Phylogenetic analysis based on ITS 2 sequences provided strong support (i.e., bootstrap value of 80%) that wild A. americanum clustered into a distinguishable group separate from those derived from colony ticks.

Animals↗

[Digitalized angiography in coronary disease].

In cardiology, digital subtraction angiography after intravenous injection of contrast medium allows only the visualization of relative large structures as the ventricles and the great vessels. Subselective intra-arterial injections are attractive, but do not provide an appreciable reduction of the injected amount of contrast medium. A reduction is possible with selective injections, but good subtraction is only possible for non-moving arteries or for arteries with truly periodic movement (ECG gated subtraction). With the improvement of spatial and temporal resolution, digital angiography (without image subtraction) could replace conventional angiography, provided that the main problem of prohibitive costs associated to the stockage of image sequences with high spatial (1024 x 1024) and temporal (25 images/s) resolution is solved. At the present, however, the cinefilm 35 mm is still unbeaten in density of information, handling and costs. In interventional cardiology, the visualization of small coronary branches and of fine, fast moving guide-wires is improved by the digitalization of the images at the source, pulsed fluoroscopy, progressive scanning of the TV camera with temporary stockage of image sequences and the selective reinforcement of the image contrast in real time. Digital angiography is also more attractive than the cinefilm in view of a better exploitation of the information contained in angiographic sequences by sophisticated, computer assisted methods. For instance, parametric imaging for analysis of the contraction and relaxation of the left ventricle, or for the visualization of the progression of contrast medium to investigate the coronary circulation, condensing in one single image the information looked for, are fields where digital angiography has given new impulses to cardiologic research.

Coronary Angiography↗

Molecular analysis of cis-regulatory sequences at the alpha-amylase locus in Drosophila melanogaster.

The Amylase locus in Drosophila melanogaster contains duplicate, divergently transcribed structural genes for alpha-amylase, AmyA and AmyB. A sensitive and reliable transient expression assay was developed for testing amylase activities produced by exogenous Amy genes in somatically transformed larvae of an amylase-null strain of flies. Alleles tested, AmyA and AmyB, came from recombinant clone lambda Dm65, which contains genomic DNA from a Canton-S strain. The transient assay was used in a deletion analysis aimed at locating cis-regulatory sequences within the 5' region of AmyB. Results suggest that upstream regulatory sequences for correct spatial expression of AmyA and AmyB in third-instar larvae are located within 446 and 430 bp of their respective starts for transcription. A sequence required for high levels of AmyB expression was located within its 5' upstream region between the base pairs at -332 and -219. AmyA does not appear to have a comparable regulatory element in its 5'-flanking sequence. Barely detectable expression of AmyB was observed when it was flanked by only 92 bp of upstream sequence. A model is proposed for incomplete coordinate control of the duplicate Amy genes.

Amino Acid Sequence↗

Regulatory elements within the murine leukemia virus enhancer regions mediate glucocorticoid responsiveness.

Enhancer elements within nonleukemogenic (Akv) and T-cell leukemogenic (SL3-3) murine leukemia viruses demonstrate strong cell type preference in transcriptional activity. These transcription elements are additionally regulated by the synthetic glucocorticoid dexamethasone, and this pattern of regulation varies according to cell type. The sequences required for dexamethasone regulation for both Akv and SL3-3 are shown to include a 17-nucleotide consensus sequence previously termed the glucocorticoid response element (GRE). Although the GREs are identical for both viral enhancers, the sequences surrounding these elements differ, as does the spatial arrangement of the GRE sequences with respect to one another. It is proposed that the spatial arrangement of the GREs, as well as their precise sequence context, determines the difference in the response to dexamethasone of the enhancers in different cell types.

Acetyltransferases↗

The POU gene ceh-18 promotes gonadal sheath cell differentiation and function required for meiotic maturation and ovulation in Caenorhabditis elegans.

In Caenorhabditis elegans, specialized contractile myoepithelial cells of the somatic gonad, the gonadal sheath cells, are closely apposed to oocytes and are required for normal meiotic maturation and ovulation. Previously we found that mutations in the ceh-18 gene, which encodes a POU-class homeoprotein expressed in sheath cells, result in oocyte defects. To determine the basis for these oocyte defects, we have used time-lapse video Nomarski microscopy to observe meiotic maturation, ovulation, and early embryogenesis in ceh-18 mutants. In ceh-18 mutants sheath cell contractions are weaker, less frequent, and uncoordinated throughout the sequence of ovulation events, and ovulation is defective. Defective ovulation can result in the formation of endomitotic oocytes in the gonad, the formation of haploid embryos, and reversals in embryonic polarity. ceh-18 mutant oocytes exhibit defects prior to nuclear envelope breakdown, suggesting that they are physiologically different from the wild type. We observed delays in meiotic maturation, as well as maturation out of the normal spatial and temporal sequence, suggesting that proximal sheath cells directly or indirectly promote and spatially restrict meiotic maturation. Analysis of sheath cell differentiation in ceh-18 mutants using antibodies to proteins of the contractile apparatus reveals that although contractile proteins are expressed, the sheath cells appear disorganized. Transmission electron microscopy reveals that ceh-18 mutant sheath cells are morphologically irregular and only loosely cover oocytes. Taken together, these observations indicate that ceh-18 is a crucial determinant of sheath cell differentiation, a function required for normal meiotic maturation and ovulation.

Animals↗

A transgene containing lacZ is expressed in primary sensory neurons in zebrafish.

In order to screen for developmentally active chromosomal domains during zebrafish embryogenesis, we generated transgenic fish by microinjecting two different lacZ reporter constructs into fertilized eggs. Transgenic fish were screened among the progeny of injected fish (F0) crossed to non-injected fish. Groups of 15 to 20 progeny of each cross were tested for lacZ expression and/or transmission of injected sequences using PCR and Southern hybridizations. Progeny from 2 of 102 fish injected with supercoiled constructs containing Rous sarcoma virus promoter sequences showed apparently spatially regulated beta-galactosidase (beta-Gal) activity. However, we were not able to detect this reporter construct in DNA from fins of F1 fish. Injections of a linear reporter construct containing mouse heat-shock promoter sequences revealed transmission of injected sequences to F1 progeny in about 6% of cases (8 of 129 fish, tested with PCR). We found one lacZ-expressing line that showed a spatially and temporally restricted expression of lacZ and, therefore, features typical characteristics of "enhancer trap" lines. In this line, lacZ expression starts at 16 hours post-fertilization in trigeminal ganglion cells. At about 24 hours lacZ expression can be detected in trigeminal ganglion neurons and Rohon-Beard neurons, indicating that the development of these two cell types shows common features. The reporter gene has integrated as a single copy. The founder fish was mosaic: 19% of its offspring (3 of 16 tested animals) carried the reporter construct in their fins; about 51% (13 of 27 tested animals) of the progeny of F1 fish were beta-Gal positive indicating full hemizygosity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Applications of DNA microarrays in biology.

DNA microarrays have enabled biology researchers to conduct large-scale quantitative experiments. This capacity has produced qualitative changes in the breadth of hypotheses that can be explored. In what has become the dominant mode of use, changes in the transcription rate of nearly all the genes in a genome, taking place in a particular tissue or cell type, can be measured in disease states, during development, and in response to intentional experimental perturbations, such as gene disruptions and drug treatments. The response patterns have helped illuminate mechanisms of disease and identify disease subphenotypes, predict disease progression, assign function to previously unannotated genes, group genes into functional pathways, and predict activities of new compounds. Directed at the genome sequence itself, microarrays have been used to identify novel genes, binding sites of transcription factors, changes in DNA copy number, and variations from a baseline sequence, such as in emerging strains of pathogens or complex mutations in disease-causing human genes. They also serve as a general demultiplexing tool to sort spatially the sequence-tagged products of highly parallel reactions performed in solution. A brief review of microarray platform technology options, and of the process steps involved in complete experiment workflows, is included.

Animals↗

Resolution improvement in thick-slab magnetic resonance digital subtraction angiography using SENSE at 3T.

PURPOSE: To evaluate the use of parallel imaging (sensitivity encoding [SENSE]) to improve spatial resolution and achieve sub-second temporal resolution in fluoroscopic contrast-enhanced, magnetic resonance digital subtraction angiography (MR-DSA). MATERIALS AND METHODS: A MR-DSA sequence was optimized on a 3-T scanner with respect to sampling bandwidth and SENSE acceleration factor subject to the constraints of half-second acquisition time and 0.6 x 1.2 mm in-plane resolution. MR-DSA with and without SENSE acceleration was then evaluated in patients with arterio-venous malformations (AVMs). RESULTS: Consistent with previously reported results and theory, SENSE factors greater than two and increasing sampling bandwidth both led to increasing image noise. Compared to lower resolution MR-DSA images with similar temporal resolution, the SENSE accelerated sequence provided better spatial resolution without notable changes in the contrast enhancement of the vascular territories of the AVMs but was hampered somewhat in the late venous phases by a reconstruction artifact. CONCLUSION: SENSE acceleration of MR-DSA by a factor of two allows improved temporal or spatial resolution without significant loss of image quality. Signal-to-noise degradation associated with higher SENSE acceleration factors are likely to necessitate other approaches to further improving resolution in MR-DSA. Clinically, SENSE accelerated MR-DSA improves the non-invasive pre- and postoperative depiction of AVM flow dynamics.

Adolescent↗

Magnetic resonance cholangiopancreatography: comparison of respiratory-triggered three-dimensional fast-recovery fast spin-echo with parallel imaging technique and breath-hold half-Fourier two-dimensional single-shot fast spin-echo technique.

PURPOSE: The aim of this study was to compare magnetic resonance cholangiopancreatography (MRCP) using respiratory-triggered (resp) three-dimensional Fourier transformation (3D) fast-recovery fast spin echo (FR-FSE) sequence with array spatial sensitivity technique (ASSET) for visualization of the pancreatobiliary system with breath-hold single thick-section and multiple thin-section MRCP using 2D single shot FSE (SSFSE) sequences. MATERIALS AND METHODS: Forty patients underwent MRCP for evaluation of pancreatobiliary abnormalities in a 1.5-T magnet. Imaging time for resp 3D FR-FSE was recorded. The ghosting and blurring artifacts, overall image quality, and delineation of the pancreatobiliary ducts were evaluated using a five-point scale. RESULTS: On multisection 2D SSFSE source images, there were the least ghosting artifacts (4.9 +/- 0.3, P < 0.05). Ghosting (3.4 +/- 0.6, P < 0.05) and blurring (4.4 +/- 0.8; P < 0.05) artifacts were the most prominent on resp 3D FR-FSE. 3D FR-FSE MRCP provided the highest rating of overall image quality (4.3 +/- 0.8, P < 0.05) and delineation of third- and second-order branches of the hepatic ducts (2.9 +/- 1.6 for third-order branches and 3.9 +/- 1.3 for second-order branches, P < 0.05). Extrahepatic bile ducts, including upper and middle portions and cystic and pancreatic ducts, were also better seen with resp 3D FR-FSE MRCP than others. CONCLUSION: MRCP with resp 3D FR-FSE using ASSET can be routinely used for acquiring information from the pancreatobiliary system.

Adult↗

External and body-centered frames of reference in spatial memory: evidence from touch.

The study reports independent effects of external and body-centered reference cues on spatial coding of an irregular sequence of haptic locations. The aim was to investigate the nature of spatial coding by using a modality that does not provide distal cues routinely. Our method isolates and combines body-centered and external spatial reference cues for irregularly placed locations, scanned along a raised-line route. Disrupting body-centered reference for the locations, by orienting the map differently to the body in the test phase than in the presentation phase, doubled errors in positioning the locations along the route in recall. Adding external reference, by giving instructions to use a surrounding frame for reference when body-centered coding was disrupted, reduced errors to near baseline (no-rotation) levels. Adding external reference cues to intact (not displaced) body-centered reference halved errors, as compared with the baseline. The results are consistent with the hypothesis that accurate spatial coding is determined by the congruence of potential reference cues from diverse sources. The new findings suggest that external and body-centered reference cues have independent additive effects on spatial coding. The sequence of locations had a significant effect in all the reference conditions, suggesting the additional use of fortuitous but distinctive local touch cues on the route. The discussion considers theoretical and practical implications of the results.

Adolescent↗