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PubMed2005

[An automatic fluorescence chemosensitivity analysis system for tumors].

The Automatic Fluorescence Chemosensitivity Analysis System (AFCAS), on the basis of image analysis, image recognition and database technologies, automatically collects the microscopic fluorescent images, inputs patient information, processes images, counts cell number, analyzes statistical data, saves and screens the reports and thus it is able to provide effective informations for assisting medical diagnosis and treatments of tumors or cancers. The AFCAS System adopts the image recognition technology of Region Chain Code and Bayesian Classification and ADO-Based database technology.

Algorithms↗

PubMed1987

Molecular cloning and sequencing of a cDNA encoding the acyl carrier protein and its flanking domains in the mammalian fatty acid synthetase.

Cloned cDNAs containing coding sequences for domains proximal to the carboxy terminus of the rat fatty acid synthetase have been isolated using an expression vector and domain-specific antibodies. The coding regions were assigned to specific domains of the multifunctional complex by identification of sequences coding for characterized peptide fragments and by recognition of sequences homologous to other monofunctional enzymes. Two clones contain the entire coding region for the acyl carrier protein domain. The sequence is flanked at the 3'-end by a region coding for the thioesterase domain and at the 5'-end by a sequence coding for a reductase, most likely the ketoreductase domain. Thus the ordering of these domain-coding regions in the fatty acid synthetase mRNA is established. The acyl carrier protein domain exhibits about 25% homology with that of the discrete monofunctional acyl carrier proteins of Escherichia coli, spinach and barley, the ketoreductase domain exhibits about 25% homology with bacterial dihydrofolate reductases and the active site of the thioesterase domain exhibits both primary and secondary structural features common to the serine proteases. These findings lend support to the hypothesis that the polyfunctional fatty acid synthetase probably arose by a complex evolutionary process involving fusion of genes coding for seven individual enzymes.

Acyl Carrier Protein↗

PubMed2006

Receptive field structures for recognition.

Localized operators, like Gabor wavelets and difference-of-gaussian filters, are considered useful tools for image representation. This is due to their ability to form a sparse code that can serve as a basis set for high-fidelity reconstruction of natural images. However, for many visual tasks, the more appropriate criterion of representational efficacy is recognition rather than reconstruction. It is unclear whether simple local features provide the stability necessary to subserve robust recognition of complex objects. In this article, we search the space of two-lobed differential operators for those that constitute a good representational code under recognition and discrimination criteria. We find that a novel operator, which we call the dissociated dipole, displays useful properties in this regard. We describe simple computational experiments to assess the merits of such dipoles relative to the more traditional local operators. The results suggest that nonlocal operators constitute a vocabulary that is stable across a range of image transformations.

Action Potentials↗

PubMed2002

Recognizing shorter coding regions of human genes based on the statistics of stop codons.

With the quick progress of the Human Genome Project, a great amount of uncharacterized DNA sequences needs to be annotated copiously by better algorithms. Recognizing shorter coding sequences of human genes is one of the most important problems in gene recognition, which is not yet completely solved. This paper is devoted to solving the issue using a new method. The distributions of the three stop codons, i.e., TAA, TAG and TGA, in three phases along coding, noncoding, and intergenic sequences are studied in detail. Using the obtained distributions and other coding measures, a new algorithm for the recognition of shorter coding sequences of human genes is developed. The accuracy of the algorithm is tested based on a larger database of human genes. It is found that the average accuracy achieved is as high as 92.1% for the sequences with length of 192 base pairs, which is confirmed by sixfold cross-validation tests. It is hoped that by incorporating the present method with some existing algorithms, the accuracy for identifying human genes from unannotated sequences would be increased.

Algorithms↗

PubMed1975

A possible model for cell-cell recognition via surface macromolecules.

Alternative possibilities for the establishment of the proper cell distribution during embryogenesis are summarized at the beginning, followed by an assessment of the examples known so far where cell-cell recognition is known to be mediated via cell surface components. In the second part the species-specific recognition process which occurs during the sorting-out of dissociated sponge cells is analysed since it may serve as a possible model for cell-cell recognition in higher animals. Three possible mechanisms for the establishment of proper cell distribution are considered. These include, first, chemotaxis: secondly, guidance of cell or cell sheet movement by extracellular matrix or by surrounding cells and thirdly, random movement followed by recognition at the final point of destination. Recognition is necessary for both of the two latter processes, i.e. for cell guidance as well as for locking the cells into their final position after random movement. Two basically different recognition mechanisms should be distinguished from each other. On the one hand cells may recognize each other with the help of macromolecules situated in or just outside of the plasmamembrane which fit to each other like enzymes and substrates or antibodies and antigens. On the other hand, cells may exchange information by exchanging cytoplasmatic components via vesicles or gap junctions. The species-specific aggregation of dissociated sponge cells is considered to be a possible model for cell-cell recognition in higher animals. A proteoglycan-like intercellular macromolecule called aggregation factor seems to mediate recognition of a given species of cells in the reaggregation process of dissociated cells. The data available at the present time suggest that a monovalent surface macromolecule (baseplate) may mediate the recognition process probably by recognizing the carbohydrate side chains of the multivalent proteoglycan aggregation factor. A cell-free system was devised to mimic this aggregation process. Addition of aggregation factor to baseplate-coated sepharose beads of approximately the size of the original sponge cells has essentially the same characteristics as the cellular system. Macromolecule-coded surface information for the recognition between cells has not been established during the embryogenesis of higher animals and remains an interesting challenge.

Animals↗

PubMed1993

Coding coenzyme handles: a hypothesis for the origin of the genetic code.

The coding coenzyme handle hypothesis suggests that useful coding preceded translation. Early adapters, the ancestors of present-day anticodons, were charged with amino acids acting as coenzymes of ribozymes in a metabolically complex RNA world. The ancestral aminoacyl-adapter synthetases could have been similar to present-day self-splicing tRNA introns. A codon-anticodon-discriminator base complex embedded in these synthetases could have played an important role in amino acid recognition. Extension of the genetic code proceeded through the take-over of nonsense codons by novel amino acids, related to already coded ones either through precursor-product relationship or physicochemical similarity. The hypothesis is open for experimental tests.

Amino Acyl-tRNA Synthetases↗

PubMed1999

Evolution of the genetic code: the nonsense, antisense, and antinonsense codes make no sense.

According to the molecular recognition theory, the complementarity of the sense and nonsense DNA strands is reflected in a complementarity of polypeptides and the corresponding nonsense polypeptides. A comparison of the sense and nonsense code matrices, and of the antisense and antinonsense code matrices, either by visual inspection or by comparing the corresponding hydrophobicity matrices (e.g. by simply adding them together), revealed no complementarity of these pairs of matrices in terms of possible attractive physical forces. Instead, it was evident that the codes divide the amino acids into two major groups: hydrophilic and hydrophobic, a division which is directly correlated with the folding property of proteins. A simple primordial genetic code distinguishing between these two types of amino acids would have been capable of generating three-dimensionally folded peptides, which could stabilize coding RNAs by forming ribonucleoprotein complexes. This evolutionary scheme is reflected in the present organisation of information processing and storage in essentially all organisms. RNAs are processed and translated into proteins by ribonucleoproteins, while other steps in information retrieval and processing, such as DNA replication, transcription, protein folding and posttranslational processing, are catalyzed by proteins. This shows that the evolution of DNA as an information storage medium was a secondary event, unrelated to the evolution of the genetic code. From the primordial hydrophilic/hydrophobic (f.ex. Leu/Arg) code, evolution proceeded by introduction of a catalytic amino acid (Ser). The further evolution of the code has mainly served to increase the number of functional hydrophilic amino acids, since there has not been a great advantage in increasing the number of structural, hydrophobic amino acids. At some stage during the evolution of the genetic code, double-stranded DNA was introduced as a maximally safe genetic copy of RNA. This required the action of highly specific enzymes, and was therefore preceded by the refinement of the genetic code. As a conclusion of this evolutionary scheme, it can be inferred that, in general only the sense strand encodes proteins.

Codon, Nonsense↗

PubMed1995

Use of document image processing in cancer registration: how and why?

The aims of the study are to test and evaluate a system for document image processing (DIP) in cancer registration and coding. The results from use of optical character recognition (OCR) and image character recognition (ICR) in the data entry process are of particular interest. Cases of cancer must be reported both by clinicians and pathologists. Annually the Registry receives 80,000 reports concerning new cases and supplementary information on patients who are registered earlier [1]. Clinicians report new cancer cases to the Cancer Registry on a special designed form. Optionally, they can use a software-based application delivered from the Registry free of charge. As a part of the DIP-system, an optical digital image processing text (ODIT) system is used in recognition of machine- and hand-printed characters. The traditional registration and coding system is run parallel to the new system. After a period of testing the DIP-system nationwide, the new system will be evaluated and compared to the traditional system. The first part of the study compared the results from three character readers (CGK, XDR, and Nestor), which have been tested on our own application-specific data in a realistic setting [2]. The test shows that over 90% of the digits and about 70% of the letters can be correctly recognized by the system [3]. Feedback is communicated to clinicians to improve the quality of hand-print in the forms. It is to be hoped that this action among others will give a better recognition result for the next part of the study. The XDR Network Reader will serve as a reader in the ODIT-system chosen for the rest of the study. The software system Open Image Link shall serve as the image manager. De facto standard software like MS-Access is used as a part of the DIP-system. The next part of the study is the main project and started at the end of June 1994. Results from the project will be presented. Does the new system produce the expected high percentage of the clinicians will optionally use the software application instead of of paper forms in reporting cancer? And at what quality of data? Will the new DIP-system be cost-effective? The results from the study and the reasons for running such a project will be discussed.

Medical Oncology↗

PubMed1998

How Cro and lambda-repressor distinguish between operators: the structural basis underlying a genetic switch.

Knowledge of the three-dimensional structures of the lambda-Cro and lambda-repressor proteins in complex with DNA has made it possible to evaluate how these proteins discriminate between different operators in phage lambda. As anticipated in previous studies, the helix-turn-helix units of the respective proteins bind in very different alignments. In Cro the recognition helices are 29 A apart and are tilted by 55 degrees with respect to each other, but bind parallel to the major groove of the DNA. In lambda-repressor [Beamer, L. J. & Pabo, C. O. (1992) J. Mol. Biol. 227, 177-196] the helices are 34 A apart and are essentially parallel to each other, but are inclined to the major grooves. The DNA is much more bent when bound by Cro than in the case with lambda-repressor. The first two amino acids of the recognition helices of the two proteins, Gln-27 and Ser-28 in Cro, and Gln-44 and Ser-45 in lambda-repressor, make very similar interactions with the invariant bps 2 and 4. There are also analogous contacts between the thymine of bp 5 and, respectively, the backbone of Ala-29 of Cro and the backbone of Gly-46 of lambda-repressor. Otherwise, however, unrelated parts of the two proteins are used in sequence-specific recognition. It appears that similar contacts to the invariant or almost invariant bps (especially 2 and 4) are used by both Cro and lambda-repressor to differentiate the operator sites as a group from other sites on the DNA. The discrimination of Cro and lambda-repressor between their different operators is more subtle and seems to be achieved primarily through differences in van der Waals contacts at bp 3', together with weaker, less direct effects at bps 5' and 8', all in the nonconsensus half of the operators. The results provide further support for the idea that there is no simple code for DNA-protein recognition.

Bacteriophage lambda↗

PubMed1999

Molecular dynamics simulation in solvent of the bacteriophage 434 cI repressor protein DNA binding domain amino acids (R1-69) in complex with its cognate operator (OR1) DNA sequence.

We investigated protein/DNA interactions, using molecular dynamics simulations computed between a 10 Angstom water layer model of the 434 cI Repressor protein DNA binding domain (DBD) amino acids (R1-69) and DNA of operator (OR1) and its flanks consisting of 28 nucleotide base pairs. Hydrogen bonding interactions were monitored. In addition, van der Waals and electrostatic interaction energies were calculated. Amino acids of the 434 cI repressor DNA recognition helix 3 formed both direct and water mediated hydrogen bonds at cognate codon-anticodon nucleotide base and backbone sites within the OR1 DNA major groove halfsites and flanking regions. In addition, hydrophilic amino acids within the loop between helix 3 and helix 4 have strong electrostatic attraction to codon-anticodon nucleotides located within the central nucleotides of the minor groove between the OR1 major groove halfsites. These interactions together induced significant structural changes in the operator DNA manifested by overtwisting of the central nucleotide base pairs and narrowing of the minor groove between the DNA major groove halfsites. Finally, these findings offer a code for site specific DNA recognition by the 434 cI repressor protein.

Amino Acid Sequence↗

PubMed1999

Normal time course of auditory recognition in schizophrenia, despite impaired precision of the auditory sensory ("echoic") memory code.

Prior studies have demonstrated impaired precision of processing within the auditory sensory memory (ASM) system in schizophrenia. This study used auditory backward masking to evaluate the degree to which such deficits resulted from impaired overall precision versus premature decay of information within the short-term auditory store. ASM performance was evaluated in 14 schizophrenic participants and 16 controls. Schizophrenic participants were severely impaired in their ability to match tones following delay. However, when no-mask performance was equated across participants, schizophrenic participants were no more susceptible to the effects of backward maskers than were controls. Thus, despite impaired precision of ASM performance, schizophrenic participants showed no deficits in the time course over which short-term representations could be used within the ASM system.

Acoustic Stimulation↗

PubMed1992

T cells and human autoimmune thyroid disease: emerging data show lack of need to invoke suppressor T cell problems.

Human T cells recognize self and foreign antigens when such antigens are processed into small peptides and bound to molecules coded for by genes of the HLA region on chromosome 6. The part of the T-cell surface which is responsible for such recognition is a set of molecules coded for by a variety of genes and known as the T-cell-receptor complex. In animal models, T cells are able to transfer autoimmune thyroiditis and T cells have, therefore, long been implicated in the etiology of human autoimmune thyroid disease (AITD). Information gained from the study of intrathyroidal T cells and thyroid antigen-specific T-cell clones has shown that in patients with Graves' disease, mainly helper T-cell clones have been obtained, whereas in autoimmune (Hashimoto's) thyroiditis cytolytic T-cell clones may be predominant. Such thyroid antigen-specific T cells have now been shown to recognize one or other of the three major thyroid-specific antigens; thyroglobulin, thyroid peroxidase, or the TSH receptor and efforts are currently in progress to characterize the T-cell epitopes of these major thyroid autoantigens. Recent findings of restricted T-cell receptor V gene use amongst intrathyroidal T cells confirm the primary role of T cells in human thyroid autoimmune processes leading to AITD. However, the mechanisms whereby such autoreactive T cells escape deletion and anergy, and how they become activated, remain uncertain. There is compelling evidence that the thyroid cell itself, by expressing HLA molecules, and presenting antigen directly to the T cells, may initiate disease, perhaps after an external insult.

Amino Acid Sequence↗

PubMed1997

The Gene-Finder computer tools for analysis of human and model organisms genome sequences.

We present a complex of new programs for promoter, 3'-processing, splice sites, coding exons and gene structure identification in genomic DNA of several model species. The human gene structure prediction program FGENEH, exon prediction-FEXH and splice site prediction-HSPL have been modified for sequence analysis of Drosophila (FGENED, FEXD and DSPL), C.elegance (FGENEN, FEXN and NSPL), Yeast (FEXY and YSPL) and Plant (FGENEA, FEXA and ASPL) genomic sequences. We recomputed all frequency and discriminant function parameters for these organisms and adjusted organism specific minimal intron lengths. An accuracy of coding region prediction for these programs is similar with the observed accuracy of FEXH and FGENEH. We have developed FEXHB and FGENEHB programs combining pattern recognition features and information about similarity of predicted exons with known sequences in protein databases. These programs have approximately 10% higher average accuracy of coding region recognition. Two new programs for human promoter site prediction (TSSG and TSSW) have been developed which use Gosh (1993) and Wingender (1994) data bases of functional motifs, respectively. POLYAH program was designed for prediction of 3'-processing regions in human genes and CDSB program was developed for bacterial gene prediction. We have developed a new approach to predict multiple genes based on double dynamic programming, that is very important for analysis of long genomic DNA fragments generated by genome sequencing projects. Analysis of uncharacterized sequences based on our methods is available through the University of Houston, Weizmann Institute of Science email servers and several Web pages at Baylor College of Medicine.

Animals↗

PubMed1999

Finding a parent in a king penguin colony: the acoustic system of individual recognition.

To be fed, a king penguin, Aptenodytes patagonicus, chick must identify the call of its parents, in the continuous background noise of the colony. To study this recognition process, we played back to the chicks parental calls with acoustic parameters modified in the temporal and frequency domains. The parental call is composed of syllables (complex sounds with harmonic series) separated by pronounced amplitude declines. Our experiments with modified signals indicate that the chick's frequency analysis of the call is not tuned towards precise peak energy values, the signal being recognized even when the carrier frequency was shifted 100 Hz down or 75 Hz up. To recognize the adult, chicks used frequency rather than amplitude modulation, in particular the frequency modulation shape of the syllable. This structure is repeated through the different syllables of the call giving a distinct vocal signature. Our experiments also show that the receiver needs to perceive only a small part of the signal: the first half of the syllable (0.23 s) and the first three harmonics were sufficient to elicit recognition. The small amount of information necessary to understand the message, the high redundancy in the time and frequency domains and the almost infinite possibilities of coding provided by the frequency modulation signature permit the chick to recognize the adult, without the help of a nest site. For these reasons, the code used in the call of the king penguin can be regarded as a functional code, increasing the possibility of individual recognition in an acoustically constraining environment. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed2003

Human hippocampal and parahippocampal activity during visual associative recognition memory for spatial and nonspatial stimulus configurations.

Evidence from animal studies points to the importance of the parahippocampal region (PHR) [including entorhinal, perirhinal, and parahippocampal (PHC) cortices] for recognition of visual stimuli. Recent findings in animals suggest that PHR may also be involved in visual associative recognition memory for configurations of stimuli. Thus far, however, such involvement has not been demonstrated in humans. In fact, it has been argued that associative recognition in humans is critically dependent on the hippocampal formation (HF). To better understand the division of function between HF and PHR during recognition memory in humans, we measured the activity of both areas in healthy young adults during an associative recognition memory task using functional magnetic resonance imaging. To more precisely characterize the nature of the associations that might be coded by the HF and PHR during recognition, subjects were required to learn and were later tested for associations based on either the spatial arrangements of two stimuli or the identity of two stimuli (a face and a tool). An area in the PHC was found to be more active for recognized old configurations than new configurations in both the spatial and identity conditions. The HF, on the other hand, was more active for recognition of new configurations than old configurations and also more active in the spatial than the identity condition. These data highlight the involvement of PHR in the long-term coding of associative relationships between stimuli and help to clarify the nature of its functional distinction from the HF.

Adult↗

PubMed2000

The categorical perception of colors and facial expressions: the effect of verbal interference.

A series of five experiments examined the categorical perception previously found for color and facial expressions. Using a two-alternative forced-choice recognition memory paradigm, it was found that verbal interference selectively removed the defining feature of categorical perception. Under verbal interference, there was no longer the greater accuracy normally observed for cross-category judgments relative to within-category judgments. The advantage for cross-category comparisons in memory appeared to derive from verbal coding both at encoding and at storage. It thus appears that while both visual and verbal codes may be employed in the recognition memory for colors and facial expressions, subjects only made use of verbal coding when demonstrating categorical perception.

Adolescent↗

PubMed2005

Principles of microRNA-target recognition.

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression in plants and animals. Although their biological importance has become clear, how they recognize and regulate target genes remains less well understood. Here, we systematically evaluate the minimal requirements for functional miRNA-target duplexes in vivo and distinguish classes of target sites with different functional properties. Target sites can be grouped into two broad categories. 5' dominant sites have sufficient complementarity to the miRNA 5' end to function with little or no support from pairing to the miRNA 3' end. Indeed, sites with 3' pairing below the random noise level are functional given a strong 5' end. In contrast, 3' compensatory sites have insufficient 5' pairing and require strong 3' pairing for function. We present examples and genome-wide statistical support to show that both classes of sites are used in biologically relevant genes. We provide evidence that an average miRNA has approximately 100 target sites, indicating that miRNAs regulate a large fraction of protein-coding genes and that miRNA 3' ends are key determinants of target specificity within miRNA families.

3' Untranslated Regions↗

PubMed1987

Immunoglobulin variable region heptamer-nonamer recognition sequence joined to rearranged D-J segment: implications for the immunoglobulin recombinase mechanism.

We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (VH) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer-nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline VH gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of VH108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A gamma 1 constant region (but not mu) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the VH heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a nonproductive recombination.

Animals↗