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Information synthesis in key parts of the cerebral cortex as the basis of subjective experience.

This paper discusses a number of principles of the organization of cerebral processes underlying subjective experiences. The concept developed here suggests that these experiences arise as a result of the synthesis of different types of information, this synthesis occurring in various parts of the cortex which have key roles in this mental function. The synthesis is made using information arriving from the external environment, information extracted from memory, and information arriving from motivational centers. The concept is based on studies of the cerebral mechanisms of perception and thought. Experiences are demonstrated to arise as a result of the synthesis, by neurons in the projectional cortex, of data describing the physical and informational properties of a stimulus; the mechanism of the synthesis is a circular movement of excitation from the projectional to the associative regions of the cortex, then to the hippocampus and motivational centers, with return of excitation to the projectional cortex. It is also demonstrated that the process of thought involves convergence of cortical connections on defined centers, which are called interaction foci. Different thought operations are associated with their own specific interaction focus topographies: in imaginative thinking, foci are located in the temporo-parietal cortex, while abstract thinking foci in the frontal cortex. It is suggested that information arriving by means of neural connections is compared and synthesized in interaction foci, and that this provides the basis for decision-making. The final part of this paper addresses the functional importance of mental phenomena and their possible effects on cerebral processes.

Cerebral Cortex↗

A new family of powerful multivariate statistical sequence analysis techniques.

A novel multivariate statistical approach is presented for extracting and exploiting intrinsic information present in our ever-growing sequence data banks. The information extraction from the sequences avoids the pitfalls of intersequence alignment by analyzing secondary invariant functions derived from the sequences in the data bank rather than the sequences themselves. Such typical invariant function is a 20 x 20 histogram of occurrences of amino acid pairs in a given sequence or fragment thereof. To illustrate the potential of the approach an analysis of 10,000 protein sequences from the National Biomedical Research Foundation Protein Identification Resource is presented, whose analysis already reveals great biological detail. For example, zeta-hemoglobin is found to lie close to amphibian and fish chi-hemoglobin which, in turn, is an important clue to the physiological function of this mammalian early embryonic hemoglobin. The multivariate statistical framework presented unifies such apparently unrelated issues as phylogenetic comparisons between a set of sequences and distance matrices between the constituents of the biological sequences. The Multivariate Statistical Sequence Analysis (MSSA) principles can be used for a wide spectrum of sequence analysis problems such as: assignment of family memberships to new sequences, validation of new incoming sequences to be entered into the database, prediction of structure from sequence, discrimination of coding from non-coding DNA regions, and automatic generation of an atlas of protein or DNA sequences. The MSSA techniques represent a self-contained approach to learning continuously and automatically from the growing stream of new sequences. The MSSA approach is particularly likely to play a significant role in major sequencing efforts such as the human genome project.

Amino Acid Sequence↗

Extraction of information on the buildup and consumption of reactive intermediates from quadruplex DNA assembly time courses.

A method was developed to detect the time course of the overall presence of intermediate species during K+-induced DNA quadruplex assembly from single-stranded d(TG4) oligonucleotides in experiments in which only the combined circular dichroisms (CD) of all species present could be measured directly. The presence of intermediate species is determined unambiguously but quantitative estimates can be made only to the extent that the CD characteristics of all intermediates are known. The method consists of (i) obtaining CD spectra of known concentrations of initial and final species to determine their molar ellipticity coefficients, (ii) carrying out CD measurements of the kinetics of quadruplex assembly reactions at two different wavelengths, chosen to give optimal differentiation between the initial and final species, and (iii) using the results of (ii) to detect discrepancies between the rates of consumption of single strands and the generation of quadruplex to infer the presence of intermediate species. The analysis was facilitated by the validation and use of biphasic exponential expressions obtained from the SAS nonlinear curve fitting procedure NLIN in place of the raw CD data. The general method is described, then applied to data from [d(TG4)4.(K+)3] quadruplex assembly experiments.

Circular Dichroism↗

A temporal constraint structure for extracting temporal information from clinical narrative.

INTRODUCTION: Time is an essential element in medical data and knowledge which is intrinsically connected with medical reasoning tasks. Many temporal reasoning mechanisms use constraint-based approaches. Our previous research demonstrates that electronic discharge summaries can be modeled as a simple temporal problem (STP). OBJECTIVE: To categorize temporal expressions in clinical narrative text and to propose and evaluate a temporal constraint structure designed to model this temporal information and to support the implementation of higher-level temporal reasoning. METHODS: A corpus of 200 random discharge summaries across 18 years was applied in a grounded approach to construct a representation structure. Then, a subset of 100 discharge summaries was used to tally the frequency of each identified time category and the percentage of temporal expressions modeled by the structure. Fifty random expressions were used to assess inter-coder agreement. RESULTS: Six main categories of temporal expressions were identified. The constructed temporal constraint structure models time over which an event occurs by constraining its starting time and ending time. It includes a set of fields for the endpoint(s) of an event, anchor information, qualitative and metric temporal relations, and vagueness. In 100 discharge summaries, 1961 of 2022 (97%) identified temporal expressions were effectively modeled using the temporal constraint structure. Inter-coder evaluation of 50 expressions yielded exact match in 90%, partial match with trivial differences in 8%, partial match with large differences in 2%, and total mismatch in 0%. CONCLUSION: The proposed temporal constraint structure embodies a sufficient and successful implementation method to encode the diversity of temporal information in discharge summaries. Placing data within the structure provides a foundational representation upon which further reasoning, including the addition of domain knowledge and other post-processing to implement an STP, can be accomplished.

Database Management Systems↗

A method for extracting muscle information from serum creatine kinase measurements--its potential value in the monitoring and management of inflammatory muscle disease.

A major problem in treating inflammatory myopathies is the very limited information available about the processes taking place. For instance serum creatine kinase levels are often dismissed as a means of gaining an understanding of what is happening or a means of monitoring a patient. This paper shall show how serum creatine kinase levels may be used to explore the processes taking place that create muscle inflammation. This is achieved by a detailed longitudinal study. Firstly, considerable laboratory data is gathered such as serum creatine kinase levels and blood pressure information. Secondly, the data is quantified using a scientific model. We shall illustrate the approach through an extensive nine-year study of a particular polymyositis patient. We identify three basic processes that may contribute to muscle inflammation and show how they may be interpreted from specific patient data. Furthermore, details are given for controlling and monitoring the disease to maximise the reduction in the muscle attack while reducing significantly the muscle inflammation and keeping the drug concentration at a minimum to ensure minimum side-effects and how to identify and handle drug-drug, drug-natural product and adverse drug interactions. Examples are given for a natural product, azathioprine and trandolapril.

Animals↗

Extracting novel information from gene expression data.

Data from high throughput technologies, such as DNA microarrays, necessitated the development of new computational methodologies for analyzing the high dimensional information contained within the gene expression data. Liao's group suggested the use of network component analysis to predict transcription factor activities by integrating gene expression data from Escherichia coli with known connectivity information between their genes and transcription factors. This introduces an approach for obtaining novel information from gene expression data.

Computational Biology↗

Extracting chemical information from spectral data with multiplicative light scattering effects by optical path-length estimation and correction.

When analyzing complex mixtures that exhibit sample-to-sample variability using spectroscopic instrumentation, the variation in the optical path length, resulting from the physical variations inherent within the individual samples, will result in significant multiplicative light scattering perturbations. Although a number of algorithms have been proposed to address the effect of multiplicative light scattering, each has associated with it a number of underlying assumptions, which necessitates additional information relating to the spectra being attained. This information is difficult to obtain in practice and frequently is not available. Thus, with a view to removing the need for the attainment of additional information, a new algorithm, optical path-length estimation and correction (OPLEC), is proposed. The methodology is applied to two near-infrared transmittance spectral data sets (powder mixture data and wheat kernel data), and the results are compared with the extended multiplicative signal correction (EMSC) and extended inverted signal correction (EISC) algorithms. Within the study, it is concluded that the EMSC algorithm cannot be applied to the wheat kernel data set due to core information for the implementation of the algorithm not being available, while the analysis of the powder mixture data using EISC resulted in incorrect conclusions being drawn and hence a calibration model whose performance was unacceptable. In contrast, OPLEC was observed to effectively mitigate the detrimental effects of physical light scattering and significantly improve the prediction accuracy of the calibration models for the two spectral data sets investigated without any additional information pertaining to the calibration samples being required.

Algorithms↗

Adapting the structure of a neural network to extract chemical information. Application to structure-odour relationships.

Two types of neural networks were used to establish relationships between chemical structure and musk odour of 79 nitrobenzenic compounds. Substituents on the five free sites of the benzene ring (one position was always occupied by a t-butyl group) were described using three volume descriptors and three electronegativity descriptors. Musk odour was coded by a binary variable. First a classical network with two hidden layers containing six and three neurons was used. This network gave a better classification (94%) than that obtained by linear discriminant analysis (81%). The odour was then predicted using a leave-ten-out procedure, with 77% of correct prediction for the whole sample. Then a dual two-way network was built to mimic the symmetry of the problem (two sides on a molecule, two muskophore patterns). This network recognized both patterns already known to chemists and gave 99% of correct classifications by taking into account substitution in all positions. As a side benefit of the modified network structure it was possible to evaluate the influence of each of 19 substituents in each of the five possible positions.

Discriminant Analysis↗

Extracting phylogenetic information from whole-genome sequencing projects: the lactic acid bacteria as a test case.

The availability of an ever increasing number of complete genome sequences of diverse prokaryotic taxa has led to the introduction of novel approaches to infer phylogenetic relationships among bacteria. In the present study the sequences of the 16S rRNA gene and nine housekeeping genes were compared with the fraction of shared putative orthologous protein-encoding genes, conservation of gene order, dinucleotide relative abundance and codon usage among 11 genomes of species belonging to the lactic acid bacteria. In general there is a good correlation between the results obtained with various approaches, although it is clear that there is a stronger phylogenetic signal in some data sets than in others, and that different parameters have different taxonomic resolutions. It appears that trees based on different kinds of information derived from whole-genome sequencing projects do not provide much additional information about the phylogenetic relationships among bacterial taxa compared to more traditional alignment-based methods. Nevertheless, it is expected that the study of these novel forms of information will have its value in taxonomy, to determine which genes are shared, when genes or sets of genes were lost in evolutionary history, to detect the presence of horizontally transferred genes and/or confirm or enhance the phylogenetic signal derived from traditional methods. Although these conclusions are based on a relatively small data set, they are largely in agreement with other studies and it is anticipated that similar trends will be observed when comparing other genomes.

Bacterial Proteins↗

Extracting hidden information from knowledge networks.

We develop a method allowing us to reconstruct individual tastes of customers from a sparsely connected network of their opinions on products, services, or each other. Two distinct phase transitions occur as the density of edges in this network is increased: Above the first, macroscopic prediction of tastes becomes possible; while above the second, all unknown opinions can be uniquely reconstructed. We illustrate our ideas using a simple Gaussian model, which we study using both field-theoretical methods and numerical simulations. We point out a potential relevance of our approach to the field of bioinformatics.

Consumer Behavior↗

Extracting biological information from DNA arrays: an unexpected link between arginine and methionine metabolism in Bacillus subtilis.

BACKGROUND: In global gene expression profiling experiments, variation in the expression of genes of interest can often be hidden by general noise. To determine how biologically significant variation can be distinguished under such conditions we have analyzed the differences in gene expression when Bacillus subtilis is grown either on methionine or on methylthioribose as sulfur source. RESULTS: An unexpected link between arginine metabolism and sulfur metabolism was discovered, enabling us to identify a high-affinity arginine transport system encoded by the yqiXYZ genes. In addition, we tentatively identified a methionine/methionine sulfoxide transport system which is encoded by the operon ytmIJKLMhisP and is presumably used in the degradation of methionine sulfoxide to methane sulfonate for sulfur recycling. Experimental parameters resulting in systematic biases in gene expression were also uncovered. In particular, we found that the late competence operons comE, comF and comG were associated with subtle variations in growth conditions. CONCLUSIONS: Using variance analysis it is possible to distinguish between systematic biases and relevant gene-expression variation in transcriptome experiments. Co-variation of metabolic gene expression pathways was thus uncovered linking nitrogen and sulfur metabolism in B. subtilis.

Arginine↗

The extraction of information from visual persistence.

Seven-letter targets were flashed for 50 msec and followed by either a blank adapting field (persisting representation of the stimulus fully available) or a series of continuous cycles of target and mask until the cumulative duration of the target matched the estimated duration of visual persistence (stimulus physically present for same interval as representation). The reportability of information from the targets in the latter case was only 50% that in the former. The interpretation is that visual persistence is an active, continuously operating process rather than a passive neural copy of the stimulus.

Form Perception↗