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Symbols as self-emergent entities in an optimization process of feature extraction and predictions.

In the mammalian cortex the early sensory processing can be characterized as feature extraction resulting in local and analogue low-level representations. As a direct consequence, these map directly to the environment, but interpretation under natural conditions is ambiguous. In contrast, high-level representations for cognitive processing, e.g. language, require symbolic representations characterized by expression and syntax. The representations are binary, structured and disambiguated. However, do these fundamental functional distinctions translate into a fundamental distinction of the respective brain areas and their anatomical and physiological properties? Here we argue that the distinction between early sensory processing and higher cognitive functions may not be based on structural differences of cortical areas; instead similar learning principles acting on input signals with different statistics give rise to the observed variations of function. Firstly, we give an account of present research describing neuronal properties at early stages of sensory systems as a consequence of an optimization process over the set of natural stimuli. Secondly, addressing a stage following early visual processing we suggest to extend the unsupervised learning scheme by including predictive processes. These contain the widely used objective of temporal coherence as a special case and are a powerful approach to resolve ambiguities. Furthermore, in combination with a prior on the bandwidth of information exchange between units it leads to a condensation of information. Thirdly, as a crucial step, not only are predictive units optimized, but the selectivity of the feature extractors are adapted to allow optimal predictability. Thus, over and beyond making useful predictions, we propose that the predictability of a stimulus be in itself a selection criterion for further processing. In a hierarchical system the combined optimization process leads to entities that represent condensed pieces of knowledge and that are not analogue anymore. Instead, these entities work as arguments in a framework of transformations that realize predictions. Thus, the criteria of predictability and condensation in an optimization of sensory representations relate directly to the two defining properties of symbols of expression and syntax. In this paper, we sketch an unsupervised learning process that gradually transforms analogue local representations into discrete binary representations by means of four hypotheses. We propose that in this optimization process acting in a hierarchical system, entities emerge at, higher levels that fulfil the criteria defining symbols, instantiating qualitatively different representations at similarly structured low and high levels.

Animals↗

Comparing Different Measures of Heat Resistance in Selected Lines of Drosophila melanogaster.

Lines of the fly Drosophila melanogaster were selected for increased knockdown resistance to heat (39 degrees C) in a long tube. One set of lines was selected following prior heat hardening (1 h at 37 degrees C) and another without hardening. Each set consisted of three replicate selection lines and three unselected controls. Lines were tested for correlated responses to selection, in order to define the nature of knockdown resistance. Selection had a large effect on knockdown resistance, but selected lines did not differ from controls for knockdown time in small vials, survival, or recovery time following exposure to heat. Selection with and without hardening influenced the hardening response in the long tube, but not in small vial assays of resistance. The hardened selection lines had decreased resistance to ethanol and a reduced dry weight, whereas the non-hardened lines did not show these changes. The same correlated responses were also evident in two generation experiments on unselected flies. Both sets of lines showed a reduction in activity when tested at 37 degrees C, but not at 25 degrees C. These results indicate that different measures of heat resistance are surprisingly unrelated, and suggest that subtle features of the selective environment influence responses and correlated responses to selection. Copyright 1997 Elsevier Science Ltd. All rights reserved

Journal Article↗

A structure-based strategy for discovery of small ligands binding to functionally unknown proteins: combination of in silico screening and surface plasmon resonance measurements.

In the postgenomic era, many researchers and organizations have been engaged in structural and functional analyses of proteins. As a part of these efforts, searching for small organic compounds that bind specifically to target proteins is quite important. In this study, we have developed a rational strategy for ligand discovery based on the three-dimensional structures of target proteins, which were elucidated by X-ray crystallography and nuclear magnetic resonance spectroscopy. The strategy has three features: (i) rapid selection of candidate compounds by in silico screening, (ii) automated preparation of sample solutions with robotics, and (iii) reliable evaluation of the candidates with surface plasmon resonance. Applying the strategy to a protein, At2g24940 from Arabidopsis thaliana, we discovered four small ligands out of a commercially available library of about 150 000 compounds. Although these compounds had only weak affinities to the target protein, with dissociation constants ranging from 68 to 120 microM, they apparently possess common structural features. They would be leads for the development of specific inhibitors/drugs for At2g24940, and provide important clues toward elucidation of the protein function.

Arabidopsis Proteins↗

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Algorithms↗

[Uveitis: an etiological study of 200 cases following a protocol].

BACKGROUND: To evaluate the usefulness of a systematic study of patients with uveitis and to assess the associated systemic diseases. METHODS: 200 patients seen in an outpatient clinic for the evaluation of uveitis between 1981 and 1988 were included in the study. Patients with eye disease associated with drug abuse or human immunodeficiency virus were excluded. The study protocol included an initial clinical and ophthalmological evaluation followed by selected specific investigations. RESULTS: Anatomical localization: anterior uveitis 122 (61%), posterior 41 (20.5%), panuveitis 30 (15%) and intermediate 7 (3.5%). ETIOLOGY: 74 cases (37%) were secondary, 101 (50.5%) were idiopathic, and 25 (12.5%) were specific syndromes of uveitis of unknown cause. Toxoplasmosis was the most common cause of infective uveitis, and ankylosing spondylitis was the most common noninfective cause. Diagnostic process: group 1, diagnosed by the ophthalmological investigation (25 cases); group 2, diagnosed on the basis of the accompanying clinical features and/or specific investigations (66 cases); and group 3, diagnosed by wider detection methods (8 cases). CONCLUSIONS: There was a remarkably high rate uveitis without etiological diagnosis. The evaluation of patients with uveitis requires a careful evaluation of ocular and systemic features, followed by selected specific investigation. The indiscriminate use of diagnostic tests is not warranted.

Adolescent↗

Gradual emergence of song selectivity in sensorimotor structures of the male zebra finch song system.

Birdsong is a model system for understanding how motor and sensory information interact to coordinate behavior. Neurons in one potential site of sensorimotor integration, the forebrain nucleus HVc, have premotor activity during singing and auditory activity during playback of the bird's own song. It is not known whether the high degree of selectivity for learned features of song observed during playback arises in HVc or also in structures afferent to HVc. We recorded in anesthetized adult zebra finches from two structures afferent to HVc: either the nucleus interfacialis (NIf) or the L1 subdivision of the field L complex, and simultaneously from a second electrode in HVc. Correlations in the bursting pattern of ongoing activity of HVc and NIf recordings were observed; these helped to localize the first electrode to NIf recording sites. Most NIf neurons exhibited song-selective responses, but as a population, they were less selective than were HVc neurons. Most L1 neurons were not song-selective. NIf neurons have also been reported to have premotor activity during singing; thus, NIf is another potential site of auditory-motor interactions in the song system. Evidence gathered to date suggests that those brain areas in the passerine forebrain that are recruited during song production also display the most selective learned auditory responses.

Acoustic Stimulation↗

Inhibition of monoamine oxidase by pirlindole analogues: 3D-QSAR and CoMFA analysis.

A series of pyrazinocarbazoles, analogues of short acting antidepressant pirlindole (2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino[3,2,1-j,k]carbazole hydrochloride), were tested as inhibitors of monoamine oxidase A (MAO-A) and B (MAO-B). Rigid analogues exhibited potent and selective inhibition of MAO-A and have size limits (X:Y:Z) of 13.0 x 7.0 x 4.4 A. Besides MAO-A inhibition flexible analogues also demonstrated potent inhibition of MAO-B and in contrast to rigid analogues their inhibitory activity did not show the dependence on these sizes. The qualitative information (steric and electrostatic coefficients) from the 3D-QSAR with CoMFA models for MAO-A and -B are different, and this information can be used to determine the structural features influencing inhibitor selectivity.

Animals↗

The fidelity of base selection by the polymerase subunit of DNA polymerase III holoenzyme.

In common with other DNA polymerases, DNA polymerase III holoenzyme of E. coli selects the biologically correct base pair with remarkable accuracy. DNA polymerase III is particularly useful for mechanistic studies because the polymerase and editing activities reside on separate subunits. To investigate the biochemical mechanism for base insertion fidelity, we have used a gel electrophoresis assay to measure kinetic parameters for the incorporation of correct and incorrect nucleotides by the polymerase (alpha) subunit of DNA polymerase III. As judged by this assay, base selection contributes a factor of roughly 10(4)-10(5) to the overall fidelity of genome duplication. The accuracy of base selection is determined mainly by the differential KM of the enzyme for correct vs. incorrect deoxynucleoside triphosphate. The misinsertion of G opposite template A is relatively efficient, comparable to that found for G opposite T. Based on a variety of other work, the G:A pair may require a special correction mechanism, possibly because of a syn-anti pairing approximating Watson-Crick geometry. We suggest that precise recognition of the equivalent geometry of the Watson-Crick base pairs may be the most critical feature for base selection.

DNA Polymerase III↗

Nucleotides from -16 to -12 determine specific promoter recognition by bacterial sigmaS-RNA polymerase.

The alternative sigma factor sigmaS, mainly active in stationary phase of growth, recognizes in vitro a -10 promoter sequence almost identical to the one for the main sigma factor, sigma70, thus raising the problem of how specific promoter recognition by sigmaS-RNA polymerase (EsigmaS) is achieved in vivo. We investigated the promoter features involved in selective recognition by EsigmaS at the strictly sigmaS-dependent aidB promoter. We show that the presence of a C nucleotide as first residue of the aidB -10 sequence (-12C), instead of the T nucleotide canonical for sigma70-dependent promoters, is the major determinant for selective recognition by EsigmaS. The presence of the -12C does not allow formation of an open complex fully proficient in transcription initiation by Esigma70. The role of -12C as specific determinant for promoter recognition by EsigmaS was confirmed by sequence analysis of known EsigmaS-dependent promoters as well as site-directed mutagenesis at the promoters of the csgB and sprE genes. We propose that EsigmaS, unlike Esigma70, can recognize both C and T as the first nucleotide in the -10 sequence. Additional promoter features such as the presence of a C nucleotide at position -13, contributing to open complex formation by EsigmaS, and a TG motif found at the unusual -16/-15 location, possibly contributing to initial binding to the promoter, also represent important factors for sigmaS-dependent transcription. We propose a new sequence, TG(N)0-2CCATA(c/a)T, as consensus -10 sequence for promoters exclusively recognized by EsigmaS.

Bacterial Proteins↗

A numerical method for calculating moments of coalescent times in finite populations with selection.

A numerical method is developed for solving a nonstandard singular system of second-order differential equations arising from a problem in population genetics concerning the coalescent process for a sample from a population undergoing selection. The nonstandard feature of the system is that there are terms in the equations that approach infinity as one approaches the boundary. The numerical recipe is patterned after the LU decomposition for tridiagonal matrices. Although there is no analytic proof that this method leads to the correct solution, various examples are presented that suggest that the method works. This method allows one to calculate the expected number of segregating sites in a random sample of n genes from a population whose evolution is described by a model which is not selectively neutral.

Genetics, Population↗

Diagnosis of gastric carcinoma by classification on feature projections.

A new classification algorithm, called benefit maximizing classifier on feature projections (BCFP), is developed and applied to the problem of diagnosis of gastric carcinoma. The domain contains records of patients with known diagnosis through gastroscopy results. Given a training set of such records, the BCFP classifier learns how to differentiate a new case in the domain. BCFP represents a concept in the form of feature projections on each feature dimension separately. Classification in the BCFP algorithm is based on a voting among the individual predictions made on each feature. In the gastric carcinoma domain, a lesion can be an indicator of one of nine different levels of gastric carcinoma, from early to late stages. The benefit of correct classification of early levels is much more than that of late cases. Also, the costs of wrong classifications are not symmetric. In the training phase, the BCFP algorithm learns classification rules that maximize the benefit of classification. In the querying phase, using these rules, the BCFP algorithm tries to make a prediction maximizing the benefit. A genetic algorithm is applied to select the relevant features. The performance of the BCFP algorithm is evaluated in terms of accuracy and running time. The rules induced are verified by experts of the domain.

Adolescent↗

A flexible measure of contextual similarity for biomedical terms.

We present a measure of contextual similarity for biomedical terms. The contextual features need to be explored, because newly coined terms are not explicitly described and efficiently stored in biomedical ontologies and their inner features (e.g. morphologic or orthographic) do not always provide sufficient information about the properties of the underlying concepts. The context of each term can be represented as a sequence of syntactic elements annotated with biomedical information retrieved from an ontology. The sequences of contextual elements may be matched approximately by edit distance defined as the minimal cost incurred by the changes (including insertion, deletion and replacement) needed to transform one sequence into the other. Our approach augments the traditional concept of edit distance by elements of linguistic and biomedical knowledge, which together provide flexible selection of contextual features and their comparison.

Computational Biology↗

Prefrontal unit activity during a delayed oculomotor task in the monkey.

1. Unit activity was recorded in the prefrontal cortex of Rhesus monkeys during performance of a delay task with two motor components, an ocular saccade and an arm movement, following a complex pattern of auditory and visual stimuli. A special feature of the paradigm was that onsets of the different sensory stimuli, orienting saccade and arm movement were dissociated in time at predetermined time intervals. 216 task-related units were recorded. Discussion of the data focuses on two groups of cells the activity of which is modified by the saccade: the signal-related pre-saccadic tonic cells and the post-saccadic tonic cells. 2. Activity of signal-related pre-saccadic tonic cells was initiated with the onset of peripheral stimuli, visual and/or auditory, and terminated with an orienting saccade. Spatial selectivity was a feature of most units. They seemed to encode the region of space cued by the stimulus. 3. Many units were visually responsive. Activation of these depended both upon retinal locus of the stimulus and the requirement they imposed on subsequent behavior. Termination of their activity demanded foveation of some visual targets, not necessarily the one which had initiated their response. 4. The majority of these signal-related pre-saccadic tonic cells responded to onset of auditory stimuli. The termination of tonic activity in these cells with foveation of the region in space from which the signal originated suggests a spatial memory process that is no longer used when the visual fixation response can signal equivalent spatial information.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗

Quantization of accumulated diffused errors in error diffusion.

Due to its high image quality and moderate computational complexity, error diffusion is a popular halftoning algorithm for use with inkjet printers. However, error diffusion is an inherently serial algorithm that requires buffering a full row of accumulated diffused error (ADE) samples. For the best performance when the algorithm is implemented in hardware, the ADE data should be stored on the chip on which the error diffusion algorithm is implemented. However, this may result in an unacceptable hardware cost. In this paper, we examine the use of quantization of the ADE to reduce the amount of data that must be stored. We consider both uniform and nonuniform quantizers. For the nonuniform quantizers, we build on the concept of tone-dependency in error diffusion, by proposing several novel feature-dependent quantizers that yield improved image quality at a given bit rate, compared to memoryless quantizers. The optimal design of these quantizers is coupled with the design of the tone-dependent parameters associated with error diffusion. This is done via a combination of the classical Lloyd-Max algorithm and the training framework for tone-dependent error diffusion. Our results show that 4-bit uniform quantization of the ADE yields the same halftone quality as error diffusion without quantization of the ADE. At rates that vary from 2 to 3 bits per pixel, depending on the selectivity of the feature on which the quantizer depends, the feature-dependent quantizers achieve essentially the same quality as 4-bit uniform quantization.

Algorithms↗

Inflammatory pathways and immune dysregulation in pediatric postoperative septic shock: A study integrating transcriptomics, machine learning and molecular docking.

This study elucidates the molecular and immune regulatory mechanisms of pediatric postoperative septic shock. Transcriptomic data were obtained from the Gene Expression Omnibus database. Differentially expressed genes were identified using the limma package, and gene co-expression modules were constructed using Weighted Gene Co-expression Network Analysis. Functional enrichment was performed via gene set enrichment analysis, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses. Immune cell infiltration was assessed using ESTIMATE and CIBERSORT. Mendelian randomization was applied to explore causal relationships between gene expression and septic shock. Feature genes were selected using machine learning algorithms, and a diagnostic nomogram model was constructed. Finally, molecular docking analysis was performed to screen and evaluate the binding affinity of traditional Chinese medicine monomers to core target proteins. A total of 1331 differentially expressed genes were identified, and the turquoise module was strongly correlated with septic shock. Enrichment analysis revealed significant activation of IL-6/JAK/STAT3, TNF-α/NF-κB, and PI3K/Akt/mTOR pathways. Immune infiltration analysis indicated suppressed immune scores and imbalances in neutrophils, macrophages, T cells, and B cells. Mendelian randomization confirmed causal associations for 6 genes, including PIM3. The predictive model based on feature genes demonstrated high diagnostic performance. Molecular docking suggested that quercetin and astramembrannin I could stably bind PIM3. This study systematically identified core genes, dysregulated immune pathways, and candidate small-molecule interventions in pediatric septic shock, providing novel insights for early diagnosis and targeted therapy.

Humans↗

Declination angle and its role in selecting surgical telescopes.

BACKGROUND: Clinicians usually expect manufacturers to provide properly adjusted surgical telescope products. However, to ensure optimal selection and adjustment, the clinician must understand certain contributing factors, particularly the optical declination angle. METHODS: The authors have developed a simple, stepwise approach for determining a clinician's optimal working posture and declination angle. This information is then applied to each specific surgical telescope to assist the clinician in ascertaining whether the telescopes comply, or can be made to comply, with the individual needs of the clinician. RESULTS: After the optimal working posture and declination angle have been identified and defined, any surgical magnification system can be evaluated for suitability and proper adjustment. CONCLUSIONS: Declination angle is a key feature in the selection and adjustment of surgical telescope systems, permitting telescopes to be adjusted to meet the clinician's needs instead of forcing the clinician to make compromises to fit the telescopes. CLINICAL IMPLICATIONS: Properly selected and well-adjusted surgical telescopes can enhance dental operating postures and positions, resulting in sound clinical ergonomics. Poor selection and adjustment can result in poor postures and positions.

Ergonomics↗

Histopathological and immunohistochemical studies of acquired tracheobronchomalacia: an autopsy case report.

A 72-year-old patient was reported to have 'saber-sheath-type' acquired tracheobronchomalacia after irradiation therapy for laryngeal cancer. The pathogenetic features of this case were demonstrated immunohistopathologically using CD68, HLA-DR, UCHL1, L26 and Ki-67 antibodies. The principal features were (a) selective destruction of the cartilage with Ki-67 stainability from the trachea to the segmental bronchi with inflammatory infiltrations of predominant T lymphocytes (UCHL1-positive) and activated macrophages (CD68-positive with marked HLA class II antigen) and (b) replacement by collagen fibers through the affected lesion. The tissues, except for the cartilage in the airway tract, were preserved without marked change, including the membranous portion. The cartilage at organs other than the airway showed no changes. We first clarified the immunohistopathology of tracheobronchomalacia. We proposed that the characteristic cell-mediated immunity against cartilage with T lymphocytes and activated macrophages in the pathogenetic features may be related to a cancer-healing tendency.

Aged↗

Surgical management of metastatic cancer in the liver.

Metastatic cancer to the liver from gastrointestinal primary should be treated with surgical resection as a first priority. Biological and physical restrictions on the dissemination of metastatic cancer result in disease dissemination isolated within the liver in selected patients. Although there are numerous prognostic features by which patients are selected for treatment, there is one overriding prognosticator that controls the decision-making process in these patients. If a patient can be made clinically disease free as a result of surgical removal of cancer from the liver, then this technical challenge should be undertaken. This surgical complete response can be expected to prolong the life of all patients made clinically disease free, and to result in survival in approximately 30% of the entire group. Regional and systemic treatment that will improve the results of a surgical complete response, need to be pursued.

Colorectal Neoplasms↗