Geometry of circular vectors and pattern recognition of shape of a boundary

This paper deals with pattern recognition of the shape of the boundary of closed figures on the basis of a circular sequence of measurements taken on the boundary at equal intervals of a suitably chosen argument with an arbitrary starting point. A distance measure between two boundaries is defined in such a way that it has zero value when the associated sequences of measurements coincide by shifting the starting point of one of the sequences. Such a distance measure, which is invariant to the starting point of the sequence of measurements, is used in identification or discrimination by the shape of the boundary of a closed figure. The mean shape of a given set of closed figures is defined, and tests of significance of differences in mean shape between populations are proposed.

Image recognition: Visual grouping, recognition, and learning

Vision extracts useful information from images. Reconstructing the three-dimensional structure of our environment and recognizing the objects that populate it are among the most important functions of our visual system. Computer vision researchers study the computational principles of vision and aim at designing algorithms that reproduce these functions. Vision is difficult: the same scene may give rise to very different images depending on illumination and viewpoint. Typically, an astronomical number of hypotheses exist that in principle have to be analyzed to infer a correct scene description. Moreover, image information might be extracted at different levels of spatial and logical resolution dependent on the image processing task. Knowledge of the world allows the visual system to limit the amount of ambiguity and to greatly simplify visual computations. We discuss how simple properties of the world are captured by the Gestalt rules of grouping, how the visual system may learn and organize models of objects for recognition, and how one may control the complexity of the description that the visual system computes.

Computer speech synthesis: its status and prospects.

Computer speech synthesis has reached a high level of performance, with increasingly sophisticated models of linguistic structure, low error rates in text analysis, and high intelligibility in synthesis from phonemic input. Mass market applications are beginning to appear. However, the results are still not good enough for the ubiquitous application that such technology will eventually have. A number of alternative directions of current research aim at the ultimate goal of fully natural synthetic speech. One especially promising trend is the systematic optimization of large synthesis systems with respect to formal criteria of evaluation. Speech recognition has progressed rapidly in the past decade through such approaches, and it seems likely that their application in synthesis will produce similar improvements.

The small ribosomal subunit from Thermus thermophilus at 4.5 Å resolution: Pattern fittings and the identification of a functional site

The electron density map of the small ribosomal subunit from Thermus thermophilus, constructed at 4.5 Å resolution, shows the recognizable morphology of this particle, as well as structural features that were interpreted as ribosomal RNA and proteins. Unbiased assignments, carried out by quantitative covalent binding of heavy atom compounds at predetermined sites, led to the localization of the surface of the ribosomal protein S13 at a position compatible with previous assignments, whereas the surface of S11 was localized at a distance of about twice its diameter from the site suggested for its center by neutron scattering. Proteins S5 and S7, whose structures have been determined crystallographically, were visually placed in the map with no alterations in their conformations. Regions suitable to host the fold of protein S15 were detected in several positions, all at a significant distance from the location of this protein in the neutron scattering map. Targeting the 16S RNA region, where mRNA docks to allow the formation of the initiation complex by a mercurated mRNA analog, led to the characterization of its vicinity.

Dual role of the nuclear factor of activated T cells insert region in DNA recognition and cooperative contacts to activator protein 1

The transcription factors nuclear factor of activated T cells (NFAT) and activator protein 1 (AP-1) coordinately regulate cytokine gene expression in activated T-cells by binding to closely juxtaposed sites in cytokine promoters. The structural basis for cooperative binding of NFAT and AP-1 to these sites, and indeed for the cooperative binding of transcription factors to composite regulatory elements in general, is not well understood. Mutagenesis studies have identified a segment of AP-1, which lies at the junction of its DNA-binding and dimerization domains (basic region and leucine zipper, respectively), as being essential for protein–protein interactions with NFAT in the ternary NFAT/AP-1/DNA complex. In a model of the ternary complex, the segment of NFAT nearest AP-1 is the Rel insert region (RIR), a feature that is notable for its hypervariability in size and in sequence amongst members of the Rel transcription factor family. Here we have used mutational analysis to study the role of the NFAT RIR in binding to DNA and AP-1. Parallel yeast one-hybrid screening assays in combination with alanine-scanning mutagenesis led to the identification of four amino acid residues in the RIR of NFAT2 (also known as NFATC1 or NFATc) that are essential for cooperativity with AP-1 (Ile-544, Glu-545, Thr-551, and Ile-553), and three residues that are involved in interactions with DNA (Lys-538, Arg-540, and Asn-541). These results were confirmed and extended through in vitro binding assays. We thus conclude that the NFAT RIR plays an essential dual role in DNA recognition and cooperative binding to AP-1 family transcription factors.

Differences in antigen recognition and cytolytic activity of CD8+ and CD8− T cells that express the same antigen-specific receptor

CD8+ and CD8− T cell lines expressing the same antigen-specific receptor [the 2C T cell receptor (TCR)] were compared for ability to bind soluble peptide-MHC and to lyse target cells. The 2C TCR on CD8− cells bound a syngeneic MHC (Kb+)-peptide complex 10–100 times less well than the same TCR on CD8+ cells, and the CD8− 2C cells lysed target cells presenting this complex very poorly. Surprisingly, however, the CD8− cells differed little from CD8+ cells in ability to bind an allogeneic MHC (Ld+)-peptide complex and to lyse target cells presenting this complex. The CD8+/CD8− difference provided an opportunity to estimate how long TCR engagements with peptide-MHC have to persist to initiate the cytolytic T cell response.

Large vortex-like structure of dipole field in computer models of liquid water and dipole-bridge between biomolecules

We propose a framework to describe the cooperative orientational motions of water molecules in liquid water and around solute molecules in water solutions. From molecular dynamics (MD) simulation a new quantity “site-dipole field” is defined as the averaged orientation of water molecules that pass through each spatial position. In the site-dipole field of bulk water we found large vortex-like structures of more than 10 Å in size. Such coherent patterns persist more than 300 ps although the orientational memory of individual molecules is quickly lost. A 1-ns MD simulation of systems consisting of two amino acids shows that the fluctuations of site-dipole field of solvent are pinned around the amino acids, resulting in a stable dipole-bridge between side-chains of amino acids. The dipole-bridge is significantly formed even for the side-chain separation of 14 Å, which corresponds to five layers of water. The way that dipole-bridge forms sensitively depends on the side-chain orientations and thereby explains the specificity in the solvent-mediated interactions between biomolecules.

Involvement of Asn-293 in stereospecific agonist recognition and in activation of the beta 2-adrenergic receptor.

To investigate the molecular mechanism for stereospecific binding of agonists to beta 2-adrenergic receptors we used receptor models to identify potential binding sites for the beta-OH-group of the ligand, which defines the chiral center. Ser-165, located in transmembrane helix IV, and Asn-293, situated in the upper half of transmembrane helix VI, were identified as potential binding sites. Mutation of Ser-165 to Ala did not change the binding of either isoproterenol isomer as revealed after transient expression in human embryonic kidney (HEK)-293 cells. In contrast, a receptor mutant in which Asn-293 was replaced by Leu showed substantial loss of stereospecific isoproterenol binding. Adenylyl cyclase stimulation by this mutant after stable expression in CHO cells confirmed the substantial loss of stereospecificity for isoproterenol. In a series of agonists the loss of affinity in the Leu-293 mutant receptor was strongly correlated with the intrinsic activity of the compounds. Full agonists showed a 10-30-fold affinity loss, whereas partial agonists had almost the same affinity for both receptors. Stereospecific recognition of antagonists was unaltered in the Leu-293 mutant receptor. These data indicate a relationship between stereospecificity and intrinsic activity of agonists and suggest that Asn-293 is important for both properties of the agonist-receptor interaction.

Self-recognition and abstraction abilities in the common chimpanzee studied with distorting mirrors.

The reactions of chimpanzees to regular mirrors and the results of the standard Gallup mark test have been well documented. In addition to using the mark test to demonstrate self-recognition in a regular mirror, we exposed six female chimpanzees to mirrors that produced distorted or multiplied self-images. Their reactions to their self-images, in terms of mirror-guided self-referenced behaviors, indicated that correct assessment of the source of the mirror image was made by each subject in each of the mirrors. Recognition of a distorted self-image implies an ability for abstraction in the subjects in that the distortion must be rationalized before self-recognition occurs. The implications of these results in terms of illuminating the relative importance of feature and contingency of movement cues to self-recognition are discussed.

Cue recognition and cue elaboration in learning from examples.

This paper describes the processes used by students to learn from worked-out examples and by working through problems. Evidence is derived from protocols of students learning secondary school mathematics and physics. The students acquired knowledge from the examples in the form of productions (condition-->action): first discovering conditions under which the actions are appropriate and then elaborating the conditions to enhance efficiency. Students devoted most of their attention to the condition side of the productions. Subsequently, they generalized the productions for broader application and acquired specialized productions for special problem classes.

A cooperative model for receptor recognition and cell adhesion: evidence from the molecular packing in the 1.6-A crystal structure of the pheromone Er-1 from the ciliated protozoan Euplotes raikovi.

The crystal structure of the pheromone Er-1 from the unicellular eukaryotic organism Euplotes raikovi was determined at 1.6 A resolution and refined to a crystallographic R factor of 19.9%. In the tightly packed crystal, two extensive intermolecular helix-helix interactions arrange the Er-1 molecules into layers. Since the putative receptor of the pheromone is a membrane-bound protein, whose extracellular C-terminal domain is identical in amino acid sequence to the soluble pheromone, the interactions found in the crystal may mimic the pheromone-receptor interactions as they occur on a cell surface. Based on this, we propose a model for the interaction between soluble pheromone molecules and their receptors. In this model, strong pheromone-receptor binding emerges as a consequence of the cooperative utilization of several weak interactions. The model offers an explanation for the results of binding studies and may also explain the adhesion between cells that occurs during mating.

D1 cap region involved in the receptor recognition and neural cell survival activity of human ciliary neurotrophic factor.

Human ciliary neurotrophic factor (hCNTF), which promotes the cell survival and differentiation of motor and other neurons, is a protein belonging structurally to the alpha-helical cytokine family. hCNTF was subjected to three-dimensional structure modeling and site-directed mutagenesis to analyze its structure-function relationship. The replacement of Lys-155 with any other amino acid residue resulted in abolishment of neural cell survival activity, and some of the Glu-153 mutant proteins had 5- to 10-fold higher biological activity. The D1 cap region (around the boundary between the CD loop and helix D) of hCNTF, including both Glu-153 and Lys-155, was shown to play a key role in the biological activity of hCNTF as one of the putative receptor-recognition sites. In this article, the D1 cap region of the 4-helix-bundle proteins is proposed to be important in receptor recognition and biological activity common to alpha-helical cytokine proteins reactive with gp130, a component protein of the receptors.