Representation and recognition of the movements of shapes

The problems posed by the representation and recognition of the movements of 3-D shapes are analysed. A representation is proposed for the movements of shapes that lie within the scope of the Marr & Nishihara (1978) 3-D model representation of static shapes. The basic problem is how to segment a stream of movement into pieces, each of which can be described separately. The representation proposed here is based upon segmenting a movement at moments when a component axis, e.g. an arm, starts to move relative to its local coordinate frame (here the torso). For example, walking is divided into a segment of the stationary states between each swing of the arms and legs, and the actual motions between the stationary points (relative to the torso, not the ground). This representation is called the state-motion-state (SMS) moving shape representation, and several examples of its application are given.     

Cyto-Sim: a formal language model and stochastic simulator of membrane-enclosed biochemical processes

MOTIVATION: Compartments and membranes are the basis of cell topology and more than 30% of the human genome codes for membrane proteins. While it is possible to represent compartments and membrane proteins in a nominal way with many mathematical formalisms used in systems biology, few, if any, explicitly model the topology of the membranes themselves. Discrete stochastic simulation potentially offers the most accurate representation of cell dynamics. Since the details of every molecular interaction in a pathway are often not known, the relationship between chemical species in not necessarily best described at the lowest level, i.e. by mass action. Simulation is a form of computer-aided analysis, relying on human interpretation to derive meaning. To improve efficiency and gain meaning in an automatic way, it is necessary to have a formalism based on a model which has decidable properties. RESULTS: We present Cyto-Sim, a stochastic simulator of membrane-enclosed hierarchies of biochemical processes, where the membranes comprise an inner, outer and integral layer. The underlying model is based on formal language theory and has been shown to have decidable properties (Cavaliere and Sedwards, 2006), allowing formal analysis in addition to simulation. The simulator provides variable levels of abstraction via arbitrary chemical kinetics which link to ordinary differential equations. In addition to its compact native syntax, Cyto-Sim currently supports models described as Petri nets, can import all versions of SBML and can export SBML and MATLAB m-files. AVAILABILITY: Cyto-Sim is available free, either as an applet or a stand-alone Java program via the web page (http://www.cosbi.eu/Rpty_Soft_CytoSim.php). Other versions can be made available upon request.     

Multi-layered representation for cell signaling pathways

To understand complex signaling pathways and networks, it is necessary to develop a formal and structured representation of the available information in a format suitable for analysis by software tools. Due to the complexity and incompleteness of the current biological knowledge about cell signaling, such a device must be able to represent cellular pathways at differing levels of details, one level of information abstract enough to convey an essential signaling flow while hiding its details and another level of information detailed enough to explain the underlying mechanisms that account for the signaling flow described at a more abstract level. We have defined a formal ontology for cell-signaling events that allows us to describe these cellular pathways at various levels of abstraction. Using this formal representation, ROSPath (reactive oxygen species-mediated signaling pathway) database system has been implemented and made available on the web (rospath.ewha.ac.kr). ROSPath is a database system for reactive oxygen species (ROS)-mediated cell signaling pathways and signaling processes in molecular detail, which facilitates a comprehensive understanding of the regulatory mechanisms in signaling pathways. ROSPath includes growth factor-, stress-, and cytokine-induced signaling pathways containing about 500 unique proteins (mostly mammalian) and their related protein states, protein complexes, protein complex states, signaling interactions, signaling steps, and pathways. It is a web-based structured repository of information on the signaling pathways of interest and provides a means for managing data produced by large-scale and high-throughput techniques such as proteomics. Also, software tools are provided for querying, displaying, and analyzing pathways, thus furnishing an integrated web environment for visualizing and manipulating ROS-mediated cell-signaling events.     

Process attributes in bio-ontologies

ABSTRACT: BACKGROUND: Biomedical processes can provide essential information about the (mal-) functioning of an organism and are thus frequently represented in biomedical terminologies and ontologies, including the GO Biological Process branch. These processes often need to be described and categorised in terms of their attributes, such as rates or regularities. The adequate representation of such process attributes has been a contentious issue in bio-ontologies recently; and domain ontologies have correspondingly developed ad hoc workarounds that compromise interoperability and logical consistency. RESULTS: We present a design pattern for the representation of process attributes that is compatible with upper ontology frameworks such as BFO and BioTop. Our solution rests on two key tenets: firstly, that many of the sorts of process attributes which are biomedically interesting can be characterised by the ways that repeated parts of such processes constitute, in combination, an overall process; secondly, that entities for which a full logical definition can be assigned do not need to be treated as primitive within a formal ontology framework. We apply this approach to the challenge of modelling and automatically classifying examples of normal and abnormal rates and patterns of heart beating processes, and discuss the expressivity required in the underlying ontology representation language. We provide full definitions for process attributes at increasing levels of domain complexity. CONCLUSIONS: We show that a logical definition of process attributes is feasible, though limited by the expressivity of DL languages so that the creation of primitives is still necessary. This finding may endorse current formal upper-ontology frameworks as a way of ensuring consistency, interoperability and clarity.     

Possible forms for dwell-time histograms from single-channel current records

Certain macromolecules embedded in the cell membranes of a variety of cells behave as gated ion-selective pores or channels. The length of time that a channel remains open or closed is not deterministic in nature and must be described in terms of relative probabilities. If channels act independently of each other and appropriate experimental conditions can be maintained, the behavior of a channel can be described by a homogeneous Markov process. Using this representation, the relative probability of observing openings (or closings) of various durations can be described by a sum of discrete components which are related to the underlying model of the kinetic behavior of the channel. Generally, these discrete components are taken to be simple decaying exponentials; however, exponentially decaying oscillatory components (as well as certain others which are discussed) are consistent with the Markov process representation. The presence of components other than simple decaying exponentials is shown to imply the violation of detailed balance in the steady-state (which requires energy), and thus, the presence of cyclic pathways in models which accurately represent the kinetic behavior of the channel. Oscillatory components, if present, will in general decay at a faster rate than the slowest decaying component, which, except under a very restricted set of conditions, will be a simple exponential.     

A unified modeling of Kanban systems using petri nets

The success of some Just In Time (JIT) systems has led to a growing interest in Kanban systems, which provide a way to implement a JIT control policy. Much work has recently been devoted to this problem, and especially many models have been developed to evaluate the performance of such systems. In this article, we focus our attention of these existing models. Each author uses his/her own representation, which is not formal in most cases, and so it is often difficult to understand the proposed model and to compare it with others. In this article, we show that Petri nets are well suited to provide a unified modeling of Kanban systems. We first propose a basic model, then show that most models encountered in the literature can easily be represented by a Petri net model. Once such a formal model is obtained, it can then be used to analyze the behavior of the system, both qualitatively and quantitatively. Some preliminary results pertaining to the quantitative analysis are presented at the end of the article.     

Model structure of a fragment of biological knowledge (cell motility)

The aim of the study is to contribute to a better understanding of some aspects of the structure of biological knowledge and to make clearer to what extent the methods of reasoning may be useful in this field when only qualitative information is available. A fragment of biological knowledge (theory of cell motility) is analysed from the logico-methodological point of view as a coherent system and the possibility of its formal representation is investigated. The analysis is based on distinguishing the main objects and their features (attributes) of which a given piece of knowledge is composed and on the values which these features may display. The features are interconnected by relations (in which various number of arguments appear) and these relations constitute the main (general, higher level) laws of a given fragment of knowledge (theory). Values of attributes are also mutually connected and these relations correspond to the detailed (lower level) laws. A computer system (in which Prolog language was used) enables to perform inference operations of progressive as well as regressive type. The main categories of reasoning procedures are described and illustrated by examples, namely a) search for conclusions which may be confronted with the actual knowledge in order to verify the system as a whole, b) formation of working hypotheses in the process of their empirical verification and explanation of facts and laws. The problem of development and modification of the system is also discussed.     

Self-reproducing systems: structure, niche relations and evolution.

A formal definition of a self-reproducing system is proposed using Petri nets. A potential self-reproducing system is a set of places in the Petri net such that the number of tokens in each place increases due to some sequence of internal transitions (a transition is called internal to the marked subset of places if at least one of its starting places and one of its terminating places belongs to that subset). An actual self-reproducing system is a system that compensates the outflow of its components by reproduction. In a suitable environment every potential self-reproducing system becomes an actual one. Each Petri net can be considered as an ecosystem with the web of ecological niches bound together with trophic and other relations. The stationary dynamics of the ecosystem is characterized by the set of filled niches. The process of evolution is described in terms of niche composition change. Perspectives of the theory of self-reproducing systems in biology are discussed.     

Formal thinking in biology: the woodlouse problem

Understanding biology increasingly depends upon the development of abstract, or formal thinking. Piaget, in describing formal, thought, illustrated its development in response to certain scientific problems. The ‘woodlouse problem’ described here, provides a biological example which can also be used to test the level of thinking reached by children. Sample data show that few pupils have begun to think at the formal level by the age of twelve years, but some progress is made by the time they are thirteen years old.     

The Relation between Geometry and Time in Mental Actions

Mental imagery is a cognitive tool that helps humans take decisions by simulating past and future events. The hypothesis has been advanced that there is a functional equivalence between actual and mental movements. Yet, we do not know whether there are any limitations to its validity even in terms of some fundamental features of actual movements, such as the relationship between space and time. Although it is impossible to directly measure the spatiotemporal features of mental actions, an indirect investigation can be conducted by taking advantage of the constraints existing in planar drawing movements and described by the two-thirds power law (2/3PL). This kinematic law describes one of the most impressive regularities observed in biological movements: movement speed decreases when curvature increases. Here, we compared the duration of identical actual and mental arm movements by changing the constraints imposed by the 2/3PL. In the first two experiments, the length of the trajectory remained constant, while its curvature (Experiment 1) or its number of inflexions (Experiment 2) was manipulated. The results showed that curvature, but not the number of inflexions, proportionally and similarly affected actual and mental movement duration, as expected from the 2/3PL. Two other control experiments confirmed that the results of Experiment 1 were not attributable to eye movements (Experiment 3) or to the perceived length of the displayed trajectory (Experiment 4). Altogether, our findings suggest that mental movement simulation is tuned to the kinematic laws characterizing actions and that kinematics of actual and mental movements is completely specified by the representation of their geometry.     

The language of RNA: a formal grammar that includes pseudoknots

MOTIVATION: In a previous paper, we presented a polynomial time dynamic programming algorithm for predicting optimal RNA secondary structure including pseudoknots. However, a formal grammatical representation for RNA secondary structure with pseudoknots was still lacking. RESULTS: Here we show a one-to-one correspondence between that algorithm and a formal transformational grammar. This grammar class encompasses the context-free grammars and goes beyond to generate pseudoknotted structures. The pseudoknot grammar avoids the use of general context-sensitive rules by introducing a small number of auxiliary symbols used to reorder the strings generated by an otherwise context-free grammar. This formal representation of the residue correlations in RNA structure is important because it means we can build full probabilistic models of RNA secondary structure, including pseudoknots, and use them to optimally parse sequences in polynomial time.     

Learning and using specific instances

A biologically plausible method for rapidly learning specific instances is described. It is contrasted with a formal model of classical conditioning (Rescorla-Wagner learning/perception training), which is shown to be relatively good for learning generalizations, but correspondingly poor for learning specific instances. A number of behaviorally relevant applications of specific instance learning are considered. For category learning, various combinations of specific instance learning and generalization are described and analyzed. Two general approaches are considered: the simple inclusion of Specific Instance Detectors (SIDs) as additional features during perception training, and specialized treatment in which SID-based categorization takes precedence over generalization-based categorization. Using the first approach, analysis and empirical results demonstrate a potential problem in representing feature presence and absence in a symmetric fashion when the frequencies of feature presence and absence are very different. However, it is shown that by using the proper representation, the addition of SIDs can only improve the convergence rate of perceptron training, the greatest improvement being achieved when SIDs are preferentially allocated for peripheral positive and negative instances. Some further improvement is possible if SIDs are treated in a specialized manner.     

Ologs: a categorical framework for knowledge representation

In this paper we introduce the olog, or ontology log, a category-theoretic model for knowledge representation (KR). Grounded in formal mathematics, ologs can be rigorously formulated and cross-compared in ways that other KR models (such as semantic networks) cannot. An olog is similar to a relational database schema; in fact an olog can serve as a data repository if desired. Unlike database schemas, which are generally difficult to create or modify, ologs are designed to be user-friendly enough that authoring or reconfiguring an olog is a matter of course rather than a difficult chore. It is hoped that learning to author ologs is much simpler than learning a database definition language, despite their similarity. We describe ologs carefully and illustrate with many examples. As an application we show that any primitive recursive function can be described by an olog. We also show that ologs can be aligned or connected together into a larger network using functors. The various methods of information flow and institutions can then be used to integrate local and global world-views. We finish by providing several different avenues for future research.     

Selection of Contaminants and Receptors of Concern for Ecological Risk Assessments Using the Paired Comparison Technique (PCT)

A critical component of the ecological risk assessment process, identification of contaminants and receptors of concern, is currently lacking an objective, data-driven, broadly applicable methodology. The paired comparison technique (PCT) can be used to meet this need by providing a standardized technique for making these decisions. PCT condenses the decision-making process down to individual components and ultimately generates an objective ranking for each alternative based on pertinent attributes. Factors considered in the PCT may be selected and weighted via a formal consensus building process which can incorporate stakeholder concerns. Once factors have been selected and weighted, each alternative is ranked relative to each other alter native for each factor. Each alternative ranking for each factor is multiplied by the factor's weight and the weighted rankings are summed. These sums are then used to rank alternatives relative to one another. This ranking provides decision-makers with a semi quantitative basis for making final decisions, although the technique itself does not (and should not) actually make the decision. Several examples of the technique using actual Superfund site data are presented.     

Motor-maps, navigation and implicit space representation in the hippocampus

Multiple sensory-motor maps located in the brainstem and the cortex are involved in spatial orientation. Guiding movements of eyes, head, neck and arms they provide an approximately linear relation between target distance and motor response. This involves especially the superior colliculus in the brainstem and the parietal cortex. There, the natural frame of reference follows from the retinal representation of the environment. A model of navigation is presented that is based on the modulation of activity in those sensory-motor maps. The actual mechanism chosen was gain-field modulation, a process of multimodal integration that has been demonstrated in the parietal cortex and superior colliculus, and was implemented as attraction to visual cues (colour). Dependent on the metric of the sensory-motor map, the relative attraction to these cues implemented as gain field modulation and their position define a fixed point attractor on the plane for locomotive behaviour. The actual implementation used Kohonen-networks in a variant of reinforcement learning that are well suited to generate such topographically organized sensory-motor maps with roughly linear visuo-motor response characteristics. In the following, it was investigated how such an implicit coding of target positions by gain-field parameters might be represented in the hippocampus formation and under what conditions a direction-invariant space representation can arise from such retinotopic representations of multiple cues. Information about the orientation in the plane—as could be provided by head direction cells—appeared to be necessary for unambiguous space representation in our model in agreement with physiological experiments. With this information, Gauss-shaped “place-cells” could be generated, however, the representation of the spatial environment was repetitive and clustered and single cells were always tuned to the gain-field parameters as well     

Live sequence charts to model medical information

ABSTRACT: BACKGROUND: Medical records accumulate data concerning patient health and the natural history of disease progression. However, methods to mine information systematically in a form other than an electronic health record are not yet available. The purpose of this study was to develop an object modeling technique as a first step towards a formal database of medical records. METHOD: Live Sequence Charts (LSC) were used to formalize the narrative text obtained during a patient interview. LSCs utilize a visual scenario-based programming language to build object models. LSC extends the classical language of UML message sequence charts (MSC), predominantly through addition of modalities and providing executable semantics. Interobject scenarios were defined to specify natural history event interactions and different scenarios in the narrative text. Result A simulated medical record was specified into LSC formalism by translating the text into an object model that comprised a set of entities and events. The entities described the participating components (i.e., doctor, patient and record) and the events described the interactions between elements. A conceptual model is presented to illustrate the approach. An object model was generated from data extracted from an actual new patient interview, where the individual was eventually diagnosed as suffering from Chronic Fatigue Syndrome (CFS). This yielded a preliminary formal designated vocabulary for CFS development that provided a basis for future formalism of these records. CONCLUSIONS: Translation of medical records into object models created the basis for a formal database of the patient narrative that temporally depicts the events preceding disease, the diagnosis and treatment approach. The LSCs object model of the medical narrative provided an intuitive, visual representation of the natural history of the patient's disease.     

Proposed partial beta-structures for lac permease and the Na+/H+ antiporter which use similar transport and H+ coupling mechanisms.

Most antiporters, symporters, and transporters have been represented as containing ten to 14 transmembrane helices, primarily on the basis of hydropathy plots. However, multihelix systems provide no obvious mechanism of transport and no simple way of distinguishing substrates. The models of lac permease and the Na+/H+ antiporter presented here postulate that beta-structures are involved in the transport of substrate, and in following this postulate arrive at readily understandable mechanisms for transport and for substrate specificity. The percentage of beta-structures necessary for these models is low enough that it is not in conflict with prior physical evidence for secondary structures. Immunological data also cannot rule these beta-structure mechanisms invalid. In lac permease the new model is obtained by formal representation of the C-terminal amino acids 243-405 as beta-strands. This formal representation nets two interchangeable beta-barrels which provide a simple mechanism for sugar transport. The alternating barrel system may comprise as little as 1/5 the entire permease. In one configuration the barrel forms a pocket with hydrogen bonding residues oriented to the outside of the cell. In the other configuration the barrel forms an analogous pocket oriented towards the inside. Six particular amino acids participate in the substrate hydrogen bonding schemes of both forms, providing a mechanism to shuttle lactose from the outside to the inside or vice versa. A trigger for change of forms which could couple the beta-barrel to H(+)-transport is easily devised, and it involves the apparently critical His322-Glu325 charge relay system. The Na+/H+ antiporter can be organized similarly with an interchanging beta-barrel-beta-clamshell structure attached to 7-transmembrane helices. Charged amino acid sidechains form the basis of an ionic shuttle which is analogous to the lactose shuttle. In this case, too, coupling of Na+ transport to H+ transport may be accomplished by a histidine-glutamate charge relay system.     

Ontology annotation: mapping genomic regions to biological function

With numerous whole genomes now in hand, and experimental data about genes and biological pathways on the increase, a systems approach to biological research is becoming essential. Ontologies provide a formal representation of knowledge that is amenable to computational as well as human analysis, an obvious underpinning of systems biology. Mapping function to gene products in the genome consists of two, somewhat intertwined enterprises: ontology building and ontology annotation. Ontology building is the formal representation of a domain of knowledge; ontology annotation is association of specific genomic regions (which we refer to simply as 'genes', including genes and their regulatory elements and products such as proteins and functional RNAs) to parts of the ontology. We consider two complementary representations of gene function: the Gene Ontology (GO) and pathway ontologies. GO represents function from the gene's eye view, in relation to a large and growing context of biological knowledge at all levels. Pathway ontologies represent function from the point of view of biochemical reactions and interactions, which are ordered into networks and causal cascades. The more mature GO provides an example of ontology annotation: how conclusions from the scientific literature and from evolutionary relationships are converted into formal statements about gene function. Annotations are made using a variety of different types of evidence, which can be used to estimate the relative reliability of different annotations.     

Fourier analysis of spike train data

A formal representation of nerve spike trains in the form of a sum of rectangular functions is proposed. This formal instantaneous frequency function can be Fourier analyzed. The resulting algorithm has the useful properties of spike by spike calculations and an insensitivity to the mean (carrier) spike rate. The technique is also useful for producing a smooth (filtered) reconstruction of a spike train.