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Generic properties of combinatory maps: neutral networks of RNA secondary structures.

Random graph theory is used to model and analyse the relationships between sequences and secondary structures of RNA molecules, which are understood as mappings from sequence space into shape space. These maps are non-invertible since there are always many orders of magnitude more sequences than structures. Sequences folding into identical structures form neutral networks. A neutral network is embedded in the set of sequences that are compatible with the given structure. Networks are modeled as graphs and constructed by random choice of vertices from the space of compatible sequences. The theory characterizes neutral networks by the mean fraction of neutral neighbors (lambda). The networks are connected and percolate sequence space if the fraction of neutral nearest neighbors exceeds a threshold value (lambda > lambda *). Below threshold (lambda < lambda *), the networks are partitioned into a largest "giant" component and several smaller components. Structures are classified as "common" or "rare" according to the sizes of their pre-images, i.e. according to the fractions of sequences folding into them. The neutral networks of any pair of two different common structures almost touch each other, and, as expressed by the conjecture of shape space covering sequences folding into almost all common structures, can be found in a small ball of an arbitrary location in sequence space. The results from random graph theory are compared to data obtained by folding large samples of RNA sequences. Differences are explained in terms of specific features of RNA molecular structures.

Base Sequence↗

A comparative study of the correction of systematic errors in the quantitation of pyrethroids in vegetables using calibration curves prepared using standards in pure solvent.

A comparative study of two mathematical approaches was performed in order to correct systematic errors due to the presence of the unexpected interferences which appear when the quantitation of the analyte in real samples is carried out with calibration curves built using standards in pure solvent. These methods consisted in the establishment of different mathematical expressions which transform the concentration (Cs) obtained using calibration graphs built using pure solvent into the corrected concentration (C(M)) that should be obtained if the quantitation is carried out with calibration curves built using standards dissolved in blank matrix extracts. In the two approaches the correction is performed from the results of an intermediate precision study which was carried out using both calibration graphs (prepared using pure solvent and blank matrix extract). By using ANCOVA to compare the slope of both solvent-based and matrix-matched calibration graphs, matrix effect was found in the determination of deltamethrin in tomato and acrinathrin in tomato and pepper. In these cases, both approaches led to good results.

Calibration↗

Convergence properties of the degree distribution of some growing network models.

In this article we study a class of randomly grown graphs that includes some preferential attachment and uniform attachment models, as well as some evolving graph models that have been discussed previously in the literature. The degree distribution is assumed to form a Markov chain; this gives a particularly simple form for a stochastic recursion of the degree distribution. We show that for this class of models the empirical degree distribution tends almost surely and in norm to the expected degree distribution as the size of the graph grows to infinity and we provide a simple asymptotic expression for the expected degree distribution. Convergence of the empirical degree distribution has consequences for statistical analysis of network data in that it allows the full data to be summarized by the degree distribution of the nodes without losing the ability to obtain consistent estimates of parameters describing the network.

Markov Chains↗

Geometry and pump function in cardiac ventricular hypertrophy.

Ventricular pump function can be quantified by the inverse relation between pressure and output, i.e., the pump function graph, which is obtained by varying arterial load without changing end-diastolic volume, inotropic state and heart rate. The ratio of pressure and output, i.e., the peripheral resistance, can be represented in the same graph by a line through the origin. The 2 pressure-output relations intersect in the working point, i.e., the pressure and flow at the prevailing steady state. In normal, anesthetized cats the ventricle appears to be matched to the arterial load in the sense that the working point is found at the optimal power, i.e., the optimal value of the product of pressure and output along the pump function graph. To maintain this matching criterion during pressure overload, the ventricular volume has to remain the same while thickening of the wall takes place: concentric hypertrophy. With volume overload, matching would be preserved with eccentric hypertrophy. Because volume and pressure overloads typically lead to eccentric and concentric hypertrophy, respectively, the matching criterion may be a valuable predictor of the geometric changes found with changes in load. This idea was further investigated experimentally by determining the position of the working point in the perinephritic cat that had 1 kidney removed and the other wrapped in cellophane for 15 to 26 weeks. The working point was no longer found at the optimal power, indicating that either matching was permanently comprised or that the ventricle was still trying to restore matching.

Animals↗

Evaluation and optimization of diagnostic tests using receiver operating characteristic analysis and information theory.

We describe a mathematical technique and an associated computer program for comparing, evaluating and optimizing diagnostic tests. The technique combines receiver operating characteristic (ROC) analysis with information theory and cost-benefit analysis to accomplish this. The program is menu driven and highly interactive; it generates 13 possible user-determined ASCII disk files which can be easily converted to graphs. These graphs allow the user to make detailed comparisons among various diagnostic tests for all values of disorder prevalence, and also provide guidelines for cut-off selection in order to optimize tests. These techniques are applied to three published studies of the enzyme screening assay for diagnosis of infection with the HIV virus. We show how graphs produced by this program can be used to compare and optimize these diagnostic tests. The program is written for an IBM-compatible microcomputer running on a DOS operating system.

Clinical Laboratory Techniques↗

Users conceptual views on medical information databases.

As information databases we consider all the kinds of information repositories that are handled by computer systems. When querying very large information databases, the end-users are often faced with the problem to parse their questions efficiently into the query languages of the computer systems. Conceptual graphs were initially designed for natural language analysis and understanding. Due to their closeness to semantic networks, their expressiveness is powerful enough to be applied to knowledge representation and use by computer systems. This work demonstrates that conceptual graphs are a suitable means to model both the information in patient databases and the queries to these databases, and that operations on graphs can compute the pattern matching process needed to provide the answers. A prototype that exploits this model is presented. Experiments have been made with the material furnished by the Unified Medical Language System project (version 2, 1992) of the National Library of Medicine, USA.

Abstracting and Indexing↗

Permanence of sparse catalytic networks.

Some global dynamical properties of catalytic networks, in particular permanence, are closely related with a directed graph representing the differential equation. It can be shown that for every directed graph with a Hamiltonian circuit there is a choice of rate constants such that the system is permanent. On the other hand, one can find properties of the graphs, for example, reducibility or the presence of endpoints, that are incompatible with permanence.

Biological Evolution↗

The reliability, acceptability and applications of basal body temperature (BBT) records in the diagnosis and treatment of infertility.

The possibilities and limitations of basal body temperature (BBT) records as an adjunct in the management of infertility were re-evaluated. To assess its accuracy as an index of ovulation, 172 charts were analyzed by three different physicians. While the average true positive rate was 90%, the false negative rate was only 2%. The remaining graphs (8%) were classified as non-interpretable, probably reflecting measurement problems. Retrospective assessment of 210 biphasic records showed the thermal nadir to occur within 1 day of the urinary luteinizing hormone (LH) surge in 75% of the cases, and in 90% when 2 days where considered. This confirms BBT as a relatively accurate guide for retrospective identification of the periovulatory period. Moreover, results of a study conducted to investigate how patients experienced daily recording of BBT graphs suggest that the method is well accepted by a high proportion of women. From all these it appears that there are many indications where BBT graphs can still be applied. Development of new electronic devices may further improve the reliability, acceptability and applications of the BBT records in the fertility investigation.

Adult↗

Estimate of the excessive spinal cord dose in AP-PA thorax treatment.

By providing quick reference graphs, we have attempted to answer the question "Does this patient need a compensating filter to keep the spinal cord dose within a certain limit?" Such graphs were obtained using several parameters that influence compensating filtration when treating the mediastinum with (anterior-posterior) parallel opposed fields. For typical 5 and 10% excess spinal cord doses above the tumor dose, the reference graphs were designed to provide quick answers for patients with the following measured parameters: (1) patient thickness at the beam axis, (2) difference in source-to-skin distances, (3) air gap between the posterior skin and the couch top, and (4) posterior spinal cord depth. 4, 10, and 18 MV photon beams were used to illustrate the results.

Humans↗

A method for the characterization of foldings in protein ribbon models.

The ribbon model of chain macromolecules is a useful tool for analyzing some of the large-scale shape features of these complex systems. Up to now, the ribbon model has been used mostly to produce graphical displays, which are usually analyzed by visual inspection. In this work we suggest a computational method for characterizing automatically, in a concise and algebraic fashion, some of the important shape features of these ribbon models. The procedure is based on a graph-theoretical and knot-theoretical characterization of three well-defined projections of a space curve associated with the ribbon. The labeled graphs can be characterized by the handedness of the crossovers in the ribbon that are the vertices of the graph. The method can be used to provide a fully algebraic representation of the changes occurring when a molecule, such as a protein, undergoes conformational rearrangements (folding), as well as to provide a shape comparison for a pair of related molecular ribbons. This algebraic representation is well suited for easy storage, retrieval, and computer manipulation of the information on the ribbon's shape. Illustrative examples of the method are provided.

Computer Graphics↗

The classification of continuous replicator pathologies.

A framework for the classification of continuous replicator (CR) pathologies expressed by cell kinetic changes, is presented. Each CR (e.g. GI mucosa or epidermis) is characterized by an origin, a periphery and a trajectory (called tissue radius) along which cells are displaced. The state of a cell on the radius is defined by two coordinates. Its distance from tissue origin 'x' expressed in cell locations, and its cruising velocity v(x), proportional to the cell production among cells separating it from origin. S(x) = x integral of o v(t)dt, represents further the net cell production associated with cell displacement from origin up to location x. The cell is regarded as a point advancing in a rectlinear motion defined by two coordinates (x,S(x)), tracing an S(x) graph outlining the proliferation differentiation states of a CR system. The S(x) graph is treated as a geometrical figure and the comparison of different CR pathologies reduces to the formulation of congruence laws. Three CR pathological entities are outlined: 1) Hemolytic pathologies e.g. hemolytic anemia, psoriasis, celiac disease and cervical erosion. 2) Hyperplastic pathologies e.g. polycythemia, papilloma and adenomatous polyp and 3) Hypoplastic pathologies e.g. aplastic anemia, skin and endometrial atrophy. Each pathology is marked by a typical S(x) graph.

Cell Transformation, Neoplastic↗

Estimation of the age of an individual based on times of eruption of permanent teeth.

This is a community based study of the times of eruption of permanent teeth to establish the age of an individual. The study is based on dental examination of 1008 subjects in the age group 5-14 years, residing in Tirupati, Andhra Pradesh, India. The median age of eruption was computed based on the concept of "Ex" which is defined as the age at which a specified percentage of individuals show eruption of a given permanent tooth. The median age "E50" was computed by transformation of percentages to probits and plotting a graph between age and probits. E50 was computed graphically corresponding to a probits value of 5.0 or 50%. A mathematical regression equation [Kusri's] was computed for each graph. The age of an individual can be computed based on the E50 value of the permanent tooth which erupted last. The probability of the given individual being above or below the assessed age can be estimated by referring to graph and probit transformation table.

Adolescent↗

A study of the effects of trend, variability, frequency, and form of data on teachers' judgments about progress and their decisions about program change.

Past research has demonstrated the influence of various factors on teachers' judgments about their students' progress. When graphed data are viewed, teachers tend to make different decisions depending upon the amount of data viewed and its trend. Current surveys of teachers' practices in data collection and decision-making indicate that teachers primarily collect training data which are examined in both graphed and ungraphed (response by response) forms to make weekly decisions about progress. In this study, 56 teachers of students with moderate to profound disabilities viewed task analytic data in one of three forms: graphed, ungraphed, or both forms. Teachers were asked to describe the progress and make a program recommendation for each student whose data they examined. Three repeated factors (trend, variability, and frequency of data collection) also were examined for their effect on the dependent variables and their interactions with data form and with each other. Results were in agreement with earlier research and further indicated that the form of the data did not produce different judgments or decisions. However, the three factors, trend, variability, and the frequency of data collection, all had significant main effects with teachers' descriptions about student progress and their program recommendations; several significant interactions among the factors also were found.

Achievement↗

Dynamic characteristics of prosthetic heart valves.

The relation between flow rate (Q) and transvalvular pressure-drop (DP) is of fundamental importance for a prosthetic heart valve tested in steady flow conditions. The Q-DP plot can thus be called the static characteristic of the valve. While in pulsatile flow, with time (t) as a parameter, the instantaneous Q(t)-DP(t) relation can also be obtained. The Q-DP relation forms a phase graph on an X-Y plane during a whole cardiac cycle, and can be regarded as the dynamic characteristic, which to our knowledge has never been systematically explored before. With in vitro experiment the Q(t)-DP(t) relations are presented for five different aortic valves. Properly modelling the characteristics of heart valves is a key link in modelling the interactions between the ventricle and arterial system. Treatments for valves, such as diode analogue and orifice area assumption governed by the Gorlin formula, are found unsatisfactory. A simple one-dimensional flow equation is used to further examine the Q-DP graph, and both the dynamic resistance characteristic and the dynamic flow characteristic can be obtained. It is found that the dynamic characteristic differs from the static one not only in the inertance effect but also in the transient process, which can be quite energy-consuming and therefore important. Geometric relations of these phase graphs with the transvalvular power loss are discussed. The method of dynamic characteristics provides a new way to evaluate the performance of a tested valve.

Biomedical Engineering↗

An intelligent tutoring system for visual classification problem solving.

OBJECTIVE: This manuscript describes the development of a general intelligent tutoring system for teaching visual classification problem solving. MATERIALS AND METHODS: The approach is informed by cognitive theory, previous empirical work on expertise in diagnostic problem-solving, and our own prior work describing the development of expertise in pathology. The architecture incorporates aspects of cognitive tutoring system and knowledge-based system design within the framework of the unified problem-solving method description language component model. Based on the domain ontology, domain task ontology and case data, the abstract problem-solving methods of the expert model create a dynamic solution graph. Student interaction with the solution graph is filtered through an instructional layer, which is created by a second set of abstract problem-solving methods and pedagogic ontologies, in response to the current state of the student model. RESULTS: In this paper, we outline the empirically derived requirements and design principles, describe the knowledge representation and dynamic solution graph, detail the functioning of the instructional layer, and demonstrate two implemented interfaces to the system. CONCLUSION: Using the general visual classification tutor, we have created SlideTutor, a tutoring system for microscopic diagnosis of inflammatory diseases of skin.

Artificial Intelligence↗

GINsim: a software suite for the qualitative modelling, simulation and analysis of regulatory networks.

This paper presents GINsim, a Java software suite devoted to the qualitative modelling, analysis and simulation of genetic regulatory networks. Formally, our approach leans on discrete mathematical and graph-theoretical concepts. GINsim encompasses an intuitive graph editor, enabling the definition and the parameterisation of a regulatory graph, as well as a simulation engine to compute the corresponding qualitative dynamical behaviour. Our computational approach is illustrated by a preliminary model analysis of the inter-cellular regulatory network activating Notch at the dorsal-ventral boundary in the wing imaginal disc of Drosophila. We focus on the cross-regulations between five genes (within and between two cells), which implements the dorsal-ventral border in the developing imaginal disc. Our simulations qualitatively reproduce the wild-type developmental pathway, as well as the outcome of various types of experimental perturbations, such as loss-of-function mutations or ectopically induced gene expression.

Animals↗

QSAR models for Daphnia toxicity of pesticides based on combinations of topological parameters of molecular structures.

A topological parameter is defined as an integer value of a given local or global invariant of a molecular graph. We examined three types of local graph invariants, the vertex degrees (0EC), the extended connectivity of first order (1EC), and the numbers of paths of length two (P2), as elementary invariants for construction of quantitative structure-activity relationships (QSAR). We also examined combined invariants, obtained by multiplying one of these three elementary types with another (i.e., [0EC.1EC], [0EC.P2], and [1EC.P2]), as graph invariants. Finally, global invariants were used in the QSAR analyses, codifying the presence and nature of cycles in the molecular structures under consideration. We used the correlation weights of these invariants to obtain optimal descriptors. These descriptors have been used in one-variable models to predict toxicity toward Daphnia magna for a set of pesticides. Statistical characteristics of the best model, based on the correlation weight of local topological parameters (the [0EC.P2]) together with the global topological parameters, are the following: n=220, r2=0.7822, s=0.849, F=783 (training set); n=42, r2=0.7388, s=0.941, F=113 (test set). The role of these topological parameters is discussed.

Animals↗

Small-world network organization of functional connectivity of EEG slow-wave activity during sleep.

OBJECTIVE: To analyze the functional connectivity patterns of the EEG slow-wave activity during the different sleep stages and Cyclic Alternating Pattern (CAP) conditions, using concepts derived from Graph Theory. METHODS: We evaluated spatial patterns of EEG slow-wave synchronization between all possible pairs of electrodes (19) placed over the scalp of 10 sleeping healthy young normal subjects using two graph theoretical measures: the clustering coefficient (Cp) and the characteristic path length (Lp). The measures were obtained during the different sleep stages and CAP conditions from the real EEG connectivity networks and randomized control (surrogate) networks (Cp-s and Lp-s). RESULTS: Cp and Cp/Cp-s increased significantly from wakefulness to sleep while Lp and Lp/Lp-s did not show changes. Cp/Cp-s was higher for A1 phases, compared to B phases of CAP. CONCLUSIONS: The network organization of the EEG slow-wave synchronization during sleep shows features characteristic of small-world networks (high Cp combined with low Lp); this type of organization is slightly but significantly more evident during the CAP A1 subtypes. SIGNIFICANCE: Our results show feasibility of using graph theoretical measures to characterize the complexity of brain networks during sleep and might indicate sleep, and the A1 phases of CAP in particular, as a period during which slow-wave synchronization shows optimal network organization for information processing.

Adult↗