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Comparison of rhyming and word generation with FMRI.

Functional magnetic resonance imaging (FMRI) has been successfully used to non-invasively map language function, but has several disadvantages. These include severe motion sensitivity, which limits overt verbal responses in behavioral paradigms, such as word generation. The lack of overt responses prevents behavioral validation, making data interpretation difficult. Our objective was to compare the FMRI activation patterns of a novel silent rhyme determination task requiring a non-verbal response, to covert word generation from visually presented letters. Five strongly right-handed subjects performed both tasks during multi-slice coronal echo-planar T2*-weighted FMRI. Single subject activation maps were generated for each task by correlation analysis of single pixel time series to a boxcar reference function. These maps for the two tasks were separately interpolated to 256(3), transformed into Talairach space, summed, and thresholded at t>6. Combined activation maps from both tasks showed similar robust perisylvian language area activation, including inferior frontal gyrus, posterior superior temporal lobe, and fusiform gyrus. Subjects performed well on the rhyming task, which activated left hemisphere cortical regions more selectively than the word generation task. The rhyming task showed less activation than the word generation task in areas typically not considered specifically related to language function, such as the dorsolateral prefrontal cortex and anterior cingulate. The rhyming task is a useful tool for brain mapping and clinical applications, potentially more specific to cortical language areas than verbal fluency.

Adult↗

Deformation tensor morphometry of semantic dementia with quantitative validation.

High-resolution structural MRI scans of 20 subjects diagnosed with semantic dementia were compared against scans of 20 cognitively normal control subjects using whole brain deformation tensor morphometry to study spatially consistent differences in local anatomical size. A fine lattice free-form volume registration algorithm was used to estimate a continuous mapping from a reference MRI to each individual subject MRI. The Jacobian of these transformations at each voxel were used to quantitatively map relative anatomical size in each individual brain. Intensity consistent filtering was applied to the determinant of these Jacobians. A careful validation using manually traced gyral anatomy was carried out and used to select an optimal deformation tensor filter scale at which to examine the anatomical size maps. General linear modeling at each voxel was used to decompose the influence of age and head size from the primary diagnosis. Maps of the T statistic of the diagnosis across the 40 subjects highlighted significant (P < 0.01 Bonferroni corrected) focal tissue contraction effects related to dementia diagnosis in the left temporal pole extending into the hippocampus, occipitotemporal gyrus and parahippocampal gyrus. Some evidence of greater focal contraction in gray over white matter was also apparent. Contraction effects were also seen, but with reduced significance in the right temporal anatomy, focused toward the temporal pole and hippocampal regions. Additional lower significance findings (P < 0.05 permutation corrected) were detected in the left superior frontal gyrus, left orbital gyrus and left parietal lobe.

Aged↗

Cleavage maps of the filamentous bacteriophages M13, fd, fl, and ZJ/2.

The replicative form DNAs of bacteriophage M13, fd, f1, and ZJ/2 were found to be sensitive to cleavage by the restriction endonucleases endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII, endoR-AluI, endoR-Hha, and endoR-Hinf. With respect to M13 DNA the number of cleavage sites varied from 21 for endoR-Hinf, 18 for endoR-AluI, 15 for endoR-Hha, 13 for endoR-HapII, 10 for endoR-HaeIII, 3 for endoR-HaeII, to only a single site for endoR-HindII. In contrast to M13, fd and f1, the ZJ/2 DNA molecule was not cleaved by the endoR-HindII endonuclease. No cleavage site on either phage DNA was detected for the endonucleases endoR-Hsu, endoR-EcoRI and endoR-Sma. When compared with M13 DNA, several differences were noted in the number and size of cleavage products obtained with DNA of phage fd, f1, and ZJ/2. From the results of these analyses, using the M13 enzyme cleavage maps as a reference, the endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII and endoR-AluI maps of phage fd, f1, and ZJ/2 could be constructed. As is expected for very closely related phages, the enzyme cleavage patterns exhibit a high degree of homology. Phage f1 and ZJ/2 are most related since an identical pattern was obtained with seven different restriction endonucleases. Evidence is provided also that f1 is more similar to M13 than to fd. Furthermore, characteristic differences exist within the endoR-Hinf enzyme cleavage pattern of all the four phages tested. Digestion of phage DNA with this enzyme, therefore, provides a new and sensitive method of distinguishing these closely related filamentous coliphages .

Chromosome Mapping↗

Electronic maps for terminal area navigation: effects of frame of reference and dimensionality.

Two experiments are reported that contrast rotating versus fixed electronic map displays, which pilots used for a simulated approach to a landing. In Experiment 1, a rotating versus fixed-map display was experimentally crossed with a two-dimensional (2D) versus three-dimensional (3D) view (perspective map) as pilots' ability to maintain the flight path and demonstrate awareness of the location of surrounding terrain features were assessed. Rotating displays supported better flight path guidance and did not substantially harm performance on terrain awareness tasks. 3D displays led to a substantial cost for vertical control but did not differ from 2D displays in lateral control. In Experiment 2, pilots flew with the rotating 2D display and with an improved version of the rotating 3D display, designed to reduce the ambiguity of representing altitude information. Vertical control improved as a result of the 3D display design improvement, but lateral control did not. The results are discussed in terms of the costs and benefits of presenting information in 3D, ego-referenced format for both flight path control and terrain awareness.

Aerospace Medicine↗

Scattering coherent and partially coherent space-time pulses through few-mode optical systems.

We consider the spatiotemporal behavior of coherent and partially coherent, pulsed, few-mode optical systems. It is shown that there is some set of orthogonal space-time pulses at the input reference surface that maps in one-to-one correspondence with some set of orthogonal space-time pulses at the output reference surface; we call these pulses eigenfields. The spectrum of the coupling coefficients determines the amount of information that can be transmitted within a given period of time. The eigenfields are unique for a given system and can be used to propagate a field that is in any state of spatial and temporal coherence. They can also be used to account for the spatial and temporal coherence of internally generated noise and to calculate the powers, fluctuations, and correlations that would be recorded by multimode detectors. Our technique is ideal for modeling the behavior of pulsed imaging arrays and interferometers.

Journal Article↗

Alignment of two genetic linkage maps on porcine chromosome 13.

A set of four microsatellite markers from the USDA genetic linkage map of porcine chromosome 13 were mapped in the European Pig Gene Mapping Project (PiGMaP) reference pedigrees. A two-point linkage analysis was performed between these markers and a set of markers known to map to chromosome 13. Pairs of markers that had a lod score greater than three were used to construct a multi-point linkage map, permitting alignment of the United States Department of Agriculture (USDA) map to the PiGMaP.

Animals↗

Pulmonary vein paced activation sequence mapping: comparison with activation sequences during onset of focal atrial fibrillation.

INTRODUCTION: Atrial fibrillation (AF) may originate from a single focus, with the vast majority observed within the pulmonary veins. To facilitate mapping, we hypothesized that there would be a characteristic right atrial endocardial activation sequence pattern associated with pacing and spontaneous focal activity from each of the four pulmonary veins. METHODS AND RESULTS: In 10 patients with focal AF, a standardized set of catheters was positioned in the right atrium. These included a 20-pole catheter along the crista terminalis, a decapolar catheter in the coronary sinus (CS), and a His-bundle electrode. Pacing (700 and 300 msec) was performed with a mapping catheter from each of the four pulmonary veins. Activation sequence maps were created by measurement of activation times to each of the recording bipoles with the proximal CS bipole as the arbitrary reference point. Similar maps were constructed for the activation sequence of the pulmonary vein ectopic that initiated AF. There was a characteristic right atrial activation map created by pacing each pulmonary vein that corresponded closely with the map from the same pulmonary vein during initiation of focal AF. The pulmonary vein of origin could be distinguished on the basis of this characteristic pattern and some stereotypic observations. CS activation occurred proximal to distal for right pulmonary veins and distal to proximal for left pulmonary veins. Significant differences in activation timing between the CS and crista terminalis differentiated upper from lower pulmonary veins. CONCLUSION: There is a characteristic right atrial activation map for activity arising from each of the four pulmonary veins that corresponded closely with the map from the same pulmonary vein during initiation of focal AF. These findings may facilitate mapping and ablation of focal AF.

Adult↗

Computerized EM maps of surface spread polytene chromosomes 1 digitizing and plotting of banding patterns.

A standard plotting program for the band-interband pattern of polytene chromosome maps was written in EXTENDED BASIC for a pocket computer coupled to a plotter (Sharp PC-1500 + CE-150). In this program, the individual polytene structure (i.e. one chromosome band and its right-handed interband) was digitized using a set of variables: [A] band diameter, [B] band type (solid, dotted, straight or curved bands), [C] band thickness, [D] interband length, [E] interband as well as puff and Balbiani ring outlines, [R] radius (for curved bands), [W] sectioning (of the pattern in chromosome maps) and [V$] reference numbers. The general use of this technique was tested by digitizing and computerized plotting of data from hand-drawn chromosome maps in Chironomus and Drosophila. Electron micrographs of surface spread polytene (SSP) chromosomes from the salivary glands of Chironomus thummi larvae were used to digitize the pattern of region F1-4 in chromosome I. The computerized EM map of this region was compared with the LM map from chromosome squash preparations.

Animals↗

A comprehensive genetic map of the human genome based on 5,264 microsatellites.

The great increase in successful linkage studies in a number of higher eukaryotes during recent years has essentially resulted from major improvements in reference genetic linkage maps, which at present consist of short tandem repeat polymorphisms of simple sequences or microsatellites. We report here the last version of the Généthon human linkage map. This map consists of 5,264 short tandem (AC/TG)n repeat polymorphisms with a mean heterozygosity of 70%. The map spans a sex-averaged genetic distance of 3,699 cM and comprises 2,335 positions, of which 2,032 could be ordered with an odds ratio of at least 1,000:1 against alternative orders. The average interval size is 1.6 cM; 59% of the map is covered by intervals of 2 cM at most and 1% remains in intervals above 10 cM.

Algorithms↗

Localization of glucose-dependent insulinotropic polypeptide (GIP) to a gene cluster on chromosome 17q.

Glucose-dependent insulinotropic polypeptide (GIP) has been regionally localized to a gene cluster on human chromosome 17q. Genetic mapping through CEPH reference families demonstrated that GIP was tightly linked to NME1 and PPY and fully linked to HOXB6 and NGFR. High-resolution radiation hybrid mapping resolved the gene order as cen-PPY-HOXB6-NGFR-GIP-NME1-tel. GIP maps distal to NGFR with an estimated distance of 250 kb.

Animals↗

[Presurgical mapping with functional MRI: comparative study with transcranial magnetic stimulation and intraoperative mapping].

PURPOSE: The accuracy of preoperative mappings in patients with brain tumors near the central sulcus using functional magnetic resonance imaging (fMRI) or transcranical magnetic stimulation (TCS) was evaluated by comparative reference to intraoperative mapping. METHODS: The thumb movement was evoked by TCS for the mapping of the motor cortex. After the placement of the marker determined by TCS on the scalp, fMRI under motor tasks consisting of repetitive grasping was performed. For motor cortex activation, an axial oblique plane to maximize gray matter sampling in the rolandic cortex was employed in order to compare these different mapping techniques more precisely. Sixteen patients with brain tumors were included in this study. RESULTS: In nine patients, fMRI disclosed activation in one restricted gyrus or in the localized area around one restricted sulcus. Of these nine patients, preoperative TCS mapping corresponded closely with fMRI in six, while in the remaining three, the TCS marker fell between 1 and 2 cm apart from the fMRI-activated area. However, in these three patients, intraoperative electrocortical stimulation corresponded with the preoperative mapping with fMRI. In six patients, contigucus two gyri were activated by motor tasks. The TCS marker was disclosed on one of the two activated gyri. Of these six patients, the position of the TCS marker and fMRI-activated site corresponded with each other in four cases. They were found on the same gyrus but there was 1.0-2.0 cm distance between them in two cases. Intraoperative somatosensory evoked potential was monitored in two of these six cases. They corresponded well with the mapping by fMRI and TCS together. In only one patient, no significant activation area was obtained by fMRI because of excessive head motion during motor tasks. The TCS marker in this patient was identical with intraoperative electro-cortical stimulation mapping. CONCLUSION: For presurgical planning in patients with brain tumor near the central sulcus, comparative evaluation with fMRI and TCS is applicable and provides accurate functional mapping.

Adult↗

An integrated approach for comparative mapping in rice and barley with special reference to the Rph16 resistance locus.

The accumulated sequence information of the almost completed rice genome and the transcriptome of other cereals provide an excellent starting point for comparative genome analysis. We performed targeted synteny-based marker saturation for the Rph16 leaf rust resistance locus in barley by extensively exploiting these newly available resources. Out of a collection of over 320,000 public barley ESTs 309 non-redundant candidate syntenic clones have been identified for this region in a two-step in silico selection procedure. For mapping, 54 barley cDNA-clones were selected due to the even distribution of their homologs on a putatively collinear 3-Mb rice BAC contig. Out of these, 97% (30) of the polymorphic markers could be genetically assigned in collinearity to the target region in barley and a set of 11 markers was integrated into an rph16 high-resolution map. Although, the collinear target region of rice does not contain an obvious candidate gene for rph16 the results demonstrate the potential of the presented procedure to efficiently utilize EST resources for synteny-based marker saturation. The systematic genome-wide exploitation of the increasing sequence data resources will strongly improve our current view of genome conservation and likely facilitate a synteny-based isolation of genes conserved across cereal species.

Chromosome Mapping↗

Sensitivity and speed of colour Doppler flow mapping compared with continuous wave Doppler for the detection of ventricular septal defects.

Twenty nine patients (aged from three months to 37 years) with confirmed or suspected ventricular septal defects were studied separately by three examiners who used colour flow mapping and imaging, or continuous wave Doppler and imaging, or a combined reference examination. Colour flow mapping identified 19 of the 25 patients with a ventricular septal defect, continuous wave Doppler echocardiography identified 18, and the combined reference examination identified 24. Two of four patients without ventricular septal defect had a false positive result with colour flow mapping and none had a false positive result with continuous wave Doppler examination. During the reference examination continuous wave Doppler identified 24 patients with ventricular septal defects and colour flow mapping identified 23. In two patients a second ventricular septal defect was found by colour flow mapping, and confirmed by continuous wave Doppler. There was no significant difference in time to diagnosis between the two techniques. Colour flow mapping aids identification of multiple ventricular septal defects but is not faster and has lower specificity than continuous wave Doppler. A combination of the two techniques gave the highest sensitivity and specificity.

Adolescent↗

Diffusion tractography based group mapping of major white-matter pathways in the human brain.

Tractography uses diffusion tensor imaging data to trace white matter pathways in vivo within the brain. We have constructed group maps that represent three major white matter tracts-the anterior callosal fibers, optic radiations, and pyramidal tracts-in a group of 21 volunteers. For each individual tract the fast marching tractography (FMT) algorithm was used to generate a VSC (voxel scale connectivity) map in native space. Using SPM99 these maps were transformed into a standard reference frame and three group mapping techniques were investigated: the first averaged the individual VSC maps, the second produced maps that demonstrate intersubject tract variability and degree of overlap, and the third used an SPM analysis to construct a statistical image that represents the group effect. The group maps reconstructed for each tract under investigation conform well to known anatomy and are consistent with data derived from postmortem human brains. Greater intersubject variability is found around the terminal projections of the tracts adjacent to cerebral cortex, whereas the "core" of each tract is characterized by lower variability. No significant differences were found between the left and right side of the pyramidal tracts and optic radiations. The group mapping techniques utilize the VSC maps in different but complementary ways. In the future, group mapping could investigate in vivo white matter differences between normal subjects and patients affected by neurological and psychiatric diseases.

Adult↗

Cross-mapping between three terminologies with the international standard nursing reference terminology model.

PURPOSE: The International Standards Organization's (ISO) International Standard IS 18104 should assist the nursing profession to integrate their terminologies into computer systems and healthcare reference terminologies. The purpose of this study is to cross-map between different terminologies; that is, to determine if concepts in one terminology are similar to concepts in another terminology. METHODS: The ISO standard was used to test the degree to which three terminologies could be cross-mapped to each other. Concepts and terms were selected, their equivalence determined by experts, and the specific concepts were dissected or broken down to their constituent parts. RESULTS: Based on experts' selections from the three classifications, equivalent concepts were identified. Those concepts deemed equivalent were dissected, thus revealing whether the components of the nursing diagnostic concepts such as focus, judgment, and other attributes of the ISO standard matched. Based on the dissection of each diagnosis, the decision was made whether mapping was possible or not. CONCLUSIONS: The dissection revealed that several nursing diagnostic concepts can easily be interchanged, while others cannot or can be mapped only for specific purposes (e.g., clinical or aggregate use). This implies that for some concepts it does not matter which terminology is used, and in other cases it does because of different meanings.

Activities of Daily Living↗

Monophasic action potential in anaesthetized guinea pigs as a biomarker for prediction of liability for drug-induced delayed ventricular repolarization.

INTRODUCTION: Drug-induced QT interval prolongation has been one of the critical issues for developing new chemical entities and pharmaceutical companies need to evaluate the risk early in the development stage. At such stage, guinea pigs are appropriate due to their small size requiring only small amounts of test drugs. The purpose of this study was to determine the utility of guinea pig monophasic action potential (MAP) using 12 reference drugs in order to clarify prediction of the QT interval prolonging risk. METHODS: Male guinea pigs were anaesthetized with pentobarbital (40 mg/kg, i.p.). Parameters analyzed were epicardial MAP duration (MAP(90)) at sinus rhythm (MAP(90(sinus))) and MAP(90) during atrial pacing (MAP(90(pacing))). Test drugs were administered to animals intravenously and cumulatively. RESULTS: Vehicle control did not affect the parameters tested. All 8 QT-prolonging drugs prolonged MAP(90(sinus)) and MAP(90(pacing)) dose-dependently, whereas all 4 non-QT-prolonging drugs showed no or very slight prolongations of these MAP(90) parameters. Rank order potency of MAP(90(pacing)) prolongations by the QT-prolonging drugs tended to correspond to clinical plasma concentrations associated with QT interval prolongations or Torsades de Pointes but showed less of a link with hERG inhibition activities. CONCLUSION: The present study demonstrates that the MAP model using anaesthetized guinea pigs could predict the liability of drugs for QT interval prolongation with high accuracy. QT assessment using the combination of the hERG assay with high sensitivity and the current in vivo assay would be desirable for early risk assessment within drug development.

Action Potentials↗

Mapping quantitative trait loci for ethanol-induced anesthesia in LSxSS recombinant inbred and F2 mice: methodology and results.

QTL (quantitative trait locus) mapping is an exciting new technique currently being applied to many quantitative traits. We review the animal models and molecular genetic techniques of QTL mapping with particular reference to ethanol-induced anesthesia (sleep time). Sleep time is an easily obtained measure of initial sensitivity to ethanol. We are using three-stage strategy to map QTLs causing the difference in sleep time between selected strains of mice. This project has been expedited by the use of polymorphic genetic markers (simple sequence repeats) which are amplifiable by the polymerase chain reaction. Over 115 strain distribution patterns have been characterized in the 27 LSxSS recombinant inbred strains. Provisional QTLs have been identified in the RI strains and will be confirmed or rejected in an F2 population of 1063 mice. A new statistical technique, interval mapping, allows the use of all polymorphic markers simultaneously to locate QTLs.

Anesthesia↗

AdDeam: a fast and scalable tool for estimating and clustering reference-level damage profiles.

MOTIVATION: DNA damage patterns, such as increased frequencies of C&#x2192;T and G&#x2192;A substitutions at fragment ends, are widely used in ancient DNA studies to assess authenticity and detect contamination. In metagenomic studies, fragments can be mapped against multiple references or de novo assembled contigs to identify those likely to be ancient. Generating and comparing damage profiles, however, can be both tedious and time-consuming. Although tools exist for estimating damage in single reference genomes and metagenomic datasets, none efficiently cluster damage patterns. RESULTS: To address this methodological gap, we developed AdDeam, a tool that combines rapid damage estimation with clustering for streamlined analyses and easy identification of potential contaminants or outliers. Our tool takes aligned ancient DNA (aDNA) fragments from various samples or contigs as input, computes damage patterns, clusters them, and outputs representative damage profiles per cluster, a probability of each sample pertaining to a cluster, as well as a Principal Component Analysis of the damage patterns for each sample for fast visualisation. We evaluated AdDeam on both simulated and empirical datasets. AdDeam effectively distinguishes different damage levels, such as uracil-DNA glycosylase-treated samples, sample-specific damages from specimens of different time periods, and can also distinguish between contigs containing modern or ancient fragments, providing a clear framework for aDNA authentication and facilitating large-scale analyses. AVAILABILITY AND IMPLEMENTATION: AdDeam is publicly available at https://github.com/LouisPwr/AdDeam and can also be installed via Bioconda. It is implemented in Python and C++. All analysis scripts and datasets are available at https://github.com/LouisPwr/AdDeamAnalysis and on Zenodo under: 10.5281/zenodo.15052427.

Software↗