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Intuitive knowledge of linguistic co-reference.

The research reported here is a systematic investigation of what competent, native speakers of English, native to contemporary syntactic theory, judge to be grammatically acceptable patterns of co-reference involving names and pronouns. Its central goal is the specification of syntactic factors that influence co-reference within and between sentences. The results show that naive subjects have consistent intuitions of grammaticality that agree with some principles of contemporary binding theory. The results also show that naive subjects diverge substantially from syntactic theorists in other judgments of grammaticality. In particular, subjects have strong intuitions that reflexives and pronouns are in complementary distribution, a fact that supports contemporary syntactic theory. Beyond that domain, subjects' judgments of co-reference in name-pronoun, name-name, and pronoun-name sequences are systematically influenced by syntactic structure in ways that are not consistent with syntactic theory. Co-reference in name-pronoun sequences is generally quite acceptable but becomes more acceptable as the syntactic prominence of the name increases. Co-reference in name-name sequences is only moderately acceptable and becomes less acceptable as the syntactic prominence of the first name increases. Co-reference in pronoun-name sequences is generally unacceptable and is only weakly influenced by the kinds of syntactic prominence that affect other relations of co-reference. We account for these results through the elaboration of a model of the process by which syntactic representations are mapped onto a representation of discourse capable of expressing generalizations about co-reference both intra-sententially and inter-sententially.

Humans↗

Permanent or transitory effects on neurocognitive components of the CNV complex induced by brain dysfunctions, lesions and ablations in humans.

Since the mid-1960s, essentially using electrophysiological methods, our research group has examined the effects of different brain diseases in humans, both on first- and second-order conditioned responses and on some types of neurocognitive potentials of the CNV complex. This didactic lecture will focus on our various attempts to identify and understand the neuroanatomical and neurophysiological substrates involved in cognitive information processing followed by the conception and execution of sensory-motor and behavioural responses evoked by significant acoustic stimuli, in both pathological situations and normal control subjects. Great interest was, e.g. aroused in the early 1970s by the rare, fortunately unrepeatable, opportunity of examining the CNV patterns in various psychiatric patients treated with psychosurgical Freeman-Watts bilateral prefrontal 'radical' lobotomy, also with repeated recordings (The Responsive Brain (1976) 158; Multidisciplinary Perspectives in Event-Related Brain-Potentials Research (1978) 376) or bimedial bifrontal cingulotomy (Multidisciplinary Perspectives in Event-Related Brain Potential Research (1978) 383). In the same period, investigations into CNV activity recorded in patients submitted to complete callosotomy ('split brain': Attention and Performance, vol. IV (1972) 221; Electroenceph. Clin. Neurophysiol. Suppl. 33 (1973) 161) were also begun and were continued into the 1980s, also with regard to other types of ERP (Brain 111 (1988) 553; J. Cog. Neurosci. 2 (1990) 258). All these data furnished unique information about the sub-second dynamics of unilateral or bihemispheric cortico-cortical and cortico-subcortical interconnections in humans. In recent years, with a classic method of analysis based on sequential scalp-topographic bidimensional neuroelectric mapping and 21/19 electrodes connected to three different references, and binaural/monaural clicks as warning signals (S1), we have repeatedly examined the CNV activity of 11 selected patients submitted to complete ablation of the damaged cortical areas, with uni- or bilateral lesions restricted to the prefrontal or associative parieto-temporal areas. We have always used the standard CNV paradigm (S1-S2 motor-response) which evokes a complex of neurocognitive potentials, including the P300 from S1, which are well-known, since they are certainly among the most studied ERPs in the various ages and races of normal subjects, psychiatric patients and subjects with different brain diseases. The most important results have been, (1) In normal subjects the MRI and the latency differences of CNV component measurements along the bidirectional pathways functionally interconnecting ipsilateral distant associative cortical areas (e.g. the arcuate-superior longitudinal complex bundle) were accounted for by the transcortical conduction time, which varies in our scalp recordings from 1 cm/0.74 to 1.28 ms ( approximately 9.8 m/s). (2) Constantly, no true auditory S1-elicited N1a, b, c, P2, N2, P300 components or CNV slow waves (O- and E-wave) were recordable over the whole of the ablated cortical areas, but only clearly identifiable volume-conducted EP/ERPs generated in other hemispheric structures. (3) The post-S1 ERP/CNV complexes on the intact hemisphere were found to be within the normal limits. (4) Effects of severe disruption on the S1 ERP/CNV complexes evocable on the site and on remote ipsilateral apparently normal anatomo-functionally interconnected brain regions were observed in 5 patients, 4 of whom had extensive frontocortical ablations. In two of the latter the distant disruptive action on the CNV components over the neuroradiologically normal ipsilateral two-way connected post-rolandic sensory and association areas was seen to be partially reversible, showing aspects of a probable slowly evolving diaschisis-like effect. Similar deactivation of some ERP components was observed in reverse on the ipsilateral dorsolateral frontocortical region in the fifth patient with a large parieto-temporal cortex ablation. These data require confirmahese data require confirmation, and when this phenomenon is observable, it must be appropriately monitored with different methods of functional neuroimaging. This will serve not only for medical and neuropsychophysiological diagnosis purposes, but also particularly for a correct and really useful planning of neuro-rehabilitation activities in selected cases.

Brain Diseases↗

Testing for interference in human genetic maps.

Known methods of testing for interference in human genetic maps are reviewed. Two aspects of interference are distinguished, numerical interference referring to the numbers of crossovers occurring and positional interference referring to the positions of crossovers. Tests for interference generally address only one or the other of these two aspects. Published investigations of interference presume fully informative marker maps, while in reality genetic markers are of limited heterozygosity, which weakens some of the tests for interference. The conclusion is drawn that rigorous tests for interference have not yet been carried out for human data.

Chromatids↗

Processing sequence annotation data using the Lua programming language.

The data processing language in a graphical software tool that manages sequence annotation data from genome databases should provide flexible functions for the tasks in molecular biology research. Among currently available languages we adopted the Lua programming language. It fulfills our requirements to perform computational tasks for sequence map layouts, i.e. the handling of data containers, symbolic reference to data, and a simple programming syntax. Upon importing a foreign file, the original data are first decomposed in the Lua language while maintaining the original data schema. The converted data are parsed by the Lua interpreter and the contents are stored in our data warehouse. Then, portions of annotations are selected and arranged into our catalog format to be depicted on the sequence map. Our sequence visualization program was successfully implemented, embedding the Lua language for processing of annotation data and layout script. The program is available at http://staff.aist.go.jp/yutaka.ueno/guppy/.

Computational Biology↗

Isolation of Listeria monocytogenes small-plaque mutants defective for intracellular growth and cell-to-cell spread.

To dissect the regulatory and structural requirements for Listeria monocytogenes intracellular growth and cell-to-cell spread, we designed a protocol based on transposon mutagenesis and the isolation of mutants which form small plaques in monolayers of mouse L2 cell fibroblasts. Two different transposable elements were used to generate libraries of insertion mutants: Tn916 and a derivative of Tn917-lac, Tn917-LTV3. Ten classes of mutants were isolated and evaluated for growth and cell-to-cell spread in J774 mouse macrophagelike cells, Henle 407 human epithelial cells, and mouse bone marrow-derived macrophages. Mutants were also evaluated for secretion of hemolysin and phospholipase (assayed by egg yolk opacity) and association with F-actin in the cytoplasm of cells, using NBD-phallacidin staining. The ten classes of mutants included (i) mutants showing abortive intracellular and extracellular growth; (ii) mutants showing abortive intracellular growth; (iii) rough mutants; (iv) mutants showing greatly reduced hemolysin and phospholipase secretion but showing normal growth in cells and little or no association with F-actin; (v) mutants with mutations mapping to an open reading frame (ORF) adjacent to hlyA and referred to as ORF U, lacking phospholipase activity, and with 50% normal hemolysin activity; (vi) mutants with reduced secretion of both hemolysin and phospholipase; (vii) nonhemolytic mutants with mutations mapping to the structural gene, hlyA; (viii) mutants with 25% normal hemolysin secretion and absolutely no association with F-actin; (ix) mutants with mutations mapping to ORF U, lacking phospholipase activity, and with normal hemolysin activity; and (x) mutants showing a mixed-plaque morphology but normal for all other parameters.

Actins↗

Drosophila as a focus in olfactory research: mapping of olfactory sensilla by fine structure, odor specificity, odorant receptor expression, and central connectivity.

This review intends to integrate recent data from the Drosophila olfactory system into an up-to-date account of the neuronal basis of olfaction. It focuses on (1) an electron microscopic study that mapped a large proportion of fruitfly olfactory sensilla, (2) large-scale electrophysiological recordings that allowed the classification of the odor response spectra of a complete set of sensilla, (3) the identification and expression patterns of candidate odorant receptors in the olfactory tissues, (4) central projections of neurons expressing a given odorant receptor, (5) an improved glomerular map of the olfactory center, and (6) attempts to exploit the larval olfactory system as a model of reduced cellular complexity. These studies find surprising parallels between the olfactory systems of flies and mammals, and thus underline the usefulness of the fruitfly as an olfactory model system. Both in Drosophila and in mammals, odorant receptor neurons appear to express only one type of receptor. Neurons expressing a given receptor are scattered in the olfactory tissues but their afferents converge onto a few target glomeruli only. This suggests that in both phyla, the periphery is represented in the brain as a chemotopic map. The major difference between mammals and fruitflies refers to the numbers of receptors, neurons, and glomeruli, which are largely reduced in the latter, and particularly in larvae. Yet, if activated in a combinatorial fashion, even this small set of elements could allow discrimination between a vast array of odorants.

Animals↗

Amyotrophic lateral sclerosis: diffusion tensor tractography and voxel-based analysis.

The purpose of this study is to investigate whether the diffusional anisotropy of water molecules is disrupted in the pyramidal and extra-pyramidal regions in patients with amyotrophic lateral sclerosis (ALS). We studied seven patients with probable ALS (four women, mean age +/- SD, 57.3 +/- 6.2 years old) according to the criteria of the World Federation of Neurology. A control group consisted of 11 age- and sex-matched volunteers (six women, 57.1 +/- 4.5) without disorders affecting the central nervous system. Voxel-based diffusion tensor analysis was made with statistical parametric mapping (SPM99). We also created the normalized corticospinal tractography from the diffusion tensor data. The significant fractional anisotropy (FA) decrease in the ALS group was found in the right frontal subgyral white matter and left frontal precentral white matter. These clusters with significant FA decrease corresponded well to the average group map of the corticospinal tract in a standard reference frame. These results suggested that the combination of voxel-based diffusion tensor analysis and diffusion tensor tractography might help determine the location of the affected neuronal tissues among ALS patients in a non-invasive manner.

Algorithms↗

High accuracy mass measurement of peptides with internal calibration using a dual electrospray ionization sprayer system for protein identification.

A dual-ESI-sprayer system was constructed and applied to achieve high accuracy of peptide mass measurement for protein identification by means of peptide mapping. Sample was introduced in one sprayer, and reference in the other, thus making internal calibration possible greatly enhancing the mass accuracy. Several samples were utilized to evaluate the reliability of this dual-ESI-sprayer system. The range of mass errors was 0.16-5.37 ppm. The peptide masses of tryptic digests of myoglobin (horse) were measured by the HPLC/dual-ESI-MS system, with mass deviations ranging from 0.01-7.67 ppm, and about 75% mass deviations below 5 ppm with 40% below 1[?]ppm. These peptide masses were utilized to perform database searching for protein identification, and compared to results obtained by external calibration. This comparison showed that the internal calibration provides a more reliable method of protein identification, with a much smaller number of required peptides for matching, and with less CPU time consumed for database searching.

Animals↗

Young people's representations of others' views of smoking: is there a link with smoking behaviour?

This paper reports a large-scale survey (n = 1985) of 9-12-year-olds' representations of parents' and friend's views about the nature of smoking. Taking the perspective of Social Representations theory, consensual representations of respondents' views of significant others are identified using cluster analysis without reference to smoking behaviour. Resulting clusters of individuals map on to self-reported behavioural groups at above chance level. These relationships indicate young smokers have access to sets of beliefs about others' smoking views that may differ systematically from those available to nonsmokers. This suggests an additional social psychological mechanism that may be implicated in early onset of smoking in adolescence.

Child↗

Construction of a statistical model for cardiac motion analysis using nonrigid image registration.

In this paper we present a new technique for tracking the movement of the myocardium using a statistical model derived from the motion fields in the hearts of several healthy volunteers. To build the statistical model we tracked the motion of the myocardium in 17 volunteers using a nonrigid registration technique based on free-form deformations and mapped the motion fields obtained into a common reference coordinate system. A principal component analysis (PCA) was then performed on the motion fields to extract the major modes of variation in the fields between the successive time frames. The modes of variation obtained were then used to parametrize the free-form deformations and build our statistical model. The results of using our model to track the motion of the heart in normal volunteers are also presented.

Algorithms↗

Probability distribution of molecular evolutionary trees: a new method of phylogenetic inference.

A new method is presented for inferring evolutionary trees using nucleotide sequence data. The birth-death process is used as a model of speciation and extinction to specify the prior distribution of phylogenies and branching times. Nucleotide substitution is modeled by a continuous-time Markov process. Parameters of the branching model and the substitution model are estimated by maximum likelihood. The posterior probabilities of different phylogenies are calculated and the phylogeny with the highest posterior probability is chosen as the best estimate of the evolutionary relationship among species. We refer to this as the maximum posterior probability (MAP) tree. The posterior probability provides a natural measure of the reliability of the estimated phylogeny. Two example data sets are analyzed to infer the phylogenetic relationship of human, chimpanzee, gorilla, and orangutan. The best trees estimated by the new method are the same as those from the maximum likelihood analysis of separate topologies, but the posterior probabilities are quite different from the bootstrap proportions. The results of the method are found to be insensitive to changes in the rate parameter of the branching process.

Animals↗

A novel microsatellite polymorphism in the human OB gene: a highly polymorphic marker for linkage analysis.

The mouse ob gene and its human homologue OB have recently been cloned. The mutations in the ob gene are known to be associated with extreme obesity. The relationship between the human OB gene and disease, however, is largely unknown due to the lack of suitable markers within or adjacent to the OB gene. To obtain informative markers, we searched for simple tandem repeat polymorphisms in the genomic sequence of the human OB gene and identified a novel tetranucleotide repeat in the 3' flanking region. Fifteen alleles were detected in this marker with a heterozygosity of 0.85 and polymorphism information content of 0.83, indicating a highly informative nature of this marker. Two-point linkage mapping in two Centre Etude Polymorphisme Humaine (CEPH) reference families suggested that this marker is located in the interval between D7S514 and D7S530, the same interval where the OB gene is located (recombination fractions with D7S514 and D7S530 were 0.026 and 0.034, respectively). Although allele frequency distributions of this marker did not differ between 84 control subjects and 69 NIDDM patients, there was a tendency to higher body weight in control subjects with class I/class I genotype than in those without this genotype (68.8 +/- 11.1 vs 60.8 +/- 10.3 kg, p = 0.05). The highly polymorphic nature of this marker and its location in the OB gene makes this marker useful for linkage studies of the OB gene with a number of phenotypes, such as obesity, non-insulin-dependent diabetes mellitus, hypertension and the insulin resistance syndrome.

Alleles↗

A limited-sampling method for evaluation of the area under the curve of ultrafilterable carboplatin in children.

Carboplatin is a widely used cytotoxic agent in numerous solid tumors of children. Since there is a large degree of interpatient variability in the area under the curve of free carboplatin for a given dose of the drug, the current tendency is to adjust the carboplatin dose so as to reach a target area under the curve rather than to determine a carboplatin dose on the basis of the body surface area. A limited-sampling method was developed for estimation of the ultrafilterable carboplatin area under the curve and for adjustment of the carboplatin dose on subsequent treatments. Population parameters were obtained from 16 children (reference group). We used the maximum a posteriori (MAP) Bayesian approach on 15 children with complete carboplatin pharmacokinetic data (test group). Two blood samples were sufficient to obtain reliable prediction of the area under the curve. The best sampling times were: (a) 30 min after the end of the infusion and (b) 5 h after the end of the infusion. On the basis of these data it is possible to prescribe prospectively a target area under the curve for free carboplatin given in a fractionated daily infusion and to adapt the carboplatin dose directly to ultrafilterable carboplatin measurements.

Adolescent↗

Comprehensive transcriptomic analysis of myostatin-knockout pigs: insights into muscle growth and lipid metabolism.

Pigs are a vital source of protein worldwide, contributing approximately 43% of global meat production. Recent genetic advancements in the myostatin (MSTN) gene have facilitated the development of double-muscling traits in livestock. In this study, we investigate the transcriptomic profiles of second-generation MSTN-knockout (MSTN-/-) pigs, generated through CRISPR/Cas9 gene editing and somatic cell nuclear transfer (SCNT). Using RNA sequencing, we compared the transcriptomic landscapes of muscle tissues from MSTN-/- pigs and wild-type (WT) counterparts. The sequencing yielded an average unique read mapping rate of 86.7% to the Sus scrofa reference genome. Our analysis revealed 15,142 differentially expressed genes (DEGs), including 121 novel genes, with 2554 genes upregulated and 1629 downregulated in the MSTN-/- group relative to the wild-type group. Notable transcriptomic changes were identified in genes associated with muscle development, lipid metabolism, and other physiological processes. These findings provide valuable insights into the molecular consequences of MSTN inactivation, with potential applications in the optimization of livestock breeding and advancements in biomedical research.

Animals↗

Scalp potential fields evoked by grating stimuli: effects of spatial frequency and orientation.

Visually evoked potentials were recorded from an array of 16 electrodes over the occipital cortex in 12 subjects. Grating stimuli of different spatial frequencies were presented on a circular test field, and potential fields evoked by vertical, horizontal and oblique stimuli were compared. Component latencies were determined by computing a reference-independent measure of field power. Scalp field maps were constructed at component latencies and compared over all conditions. Significant influences of both spatial frequency and orientation on component latencies were found. Component latencies were shortest for 2.3 c/deg gratings, and for vertically oriented stimuli. Latencies increased for horizontal, and further for oblique, gratings. The effect of spatial frequency or orientation on the location of the major components on the scalp was less pronounced. On the other hand, there were significant differences both in component latency and scalp distribution when upper and lower hemiretinal stimuli were compared. Upper hemiretinal stimulation yielded shorter latencies and a more anteriorly located potential peak on the scalp.

Adult↗

Data-determined window size and space-oriented segmentation of spontaneous EEG map series.

For the segmentation of series of momentary potential distribution maps into epochs of quasi-stable landscape (brain electric microstates), the maps are reduced to extracted landscape descriptors. Changes of the descriptors over time are recognized as segment terminators. The selection of the descriptors' tolerated variance (the window size) determines the result. We present a window-determining function which allows a data-driven determination of the optimal window size, based on equal weight given to the recognition of similarity and dissimilarity between maps. Segmentations based on two map descriptors (locations of extreme potentials and centroids) were used on 211 two-second map epochs from 8 normal subjects for validation of the window-determining function and to establish normative data. Using the data-determined window sizes for segmentation, the mean duration of the obtained microstates across subjects did not differ between descriptors (144 and 143 msec, respectively). Random permutation of the maps in time produced significantly shorter segments, ensuring that the segmentation disclosed real properties of the original data and not artifacts of the procedure.

Adult↗

Isoelectric focusing of tryptic peptides from hemoglobin subunits by immobilized pH gradients.

The technique of isoelectric focusing on immobilized pH gradients (IPG) has been applied to the analysis of tryptic digests of alpha- and beta-chains of human hemoglobin. Using peptides purified by RP-HPLC as a reference, it was possible to create a peptide map in the single IEF dimension. Unfortunately, it was not possible to find experimental conditions (medium for migration and staining) which would allow the detection of peptides of less than 10-12 residues. Almost all the bands visible on the gel could be assigned to known peptides. In order to obtain these results the IPG runs were performed in 8 M urea containing 0.5% carrier ampholytes and the gel stained with colloidal Coomassie brilliant blue G-250, in the presence of a high-salt concentration and at acidic pH.

Chromatography, High Pressure Liquid↗

The case against the case against group studies.

We challenge the position that only the analysis of single patients can allow us to infer normal function from impaired performance. We claim that the focus on group vs. single case studies is unprofitable and that a more useful question is how best to form abstractions of relevance to cognitive theory. In this context, we consider issues concerning the category of "agrammatism."

Aphasia↗