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PubMed1992

Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion.

Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed.

Animals↗

PubMed1996

Measuring fit at the implant prosthodontic interface.

Four centers in the United States and Sweden have been working for 2 years to develop systems and methods for measuring fit at the prosthodontic interface. Two systems are based on stylus contact techniques, one system uses a laser as its reader source, and one system is photogrammetric. All the systems are capable of providing data as three-dimensional x, y, and z axes coordinate values that can be transformed into linear and angular data that characterize the bearing surfaces of abutments or abutment replicas and their mating components in the prosthesis framework. The centroid, a single point computed from the collected data, was the measurement unit, derived for these bearing surfaces, that was used to compare the systems. All four methods can most likely detect misfits that are relevant in the clinical setting; however, only one system can be used intraorally. When any measurement system is assessed, the data should always be examined for repeatability to establish the reliability of the system. This investigation made comparisons among the measurement methods used at the four centers. It was apparent from this study that comparisons of data from measurement systems should be rounded to the nearest 10 microns. The SDs determined in the comparisons were larger than 5 microns and therefore misfits should be calculated in terms smaller than 10 microns. This final point is important to the clinician who relies on research reports about precision of fit when selecting treatment approaches in caring for the implant prosthodontic needs of their patients.

Calibration↗

PubMed1999

Speechreading: illusion or window into pattern recognition.

In the Fuzzy Logical Model of Perception (FLMP) perceivers are conceptualized as forming perceptual judgments by evaluating and integrating multiple ambiguous sources of information, in an optimal manner based on relative goodness of match. This model has been tested favorably against a variety of competing theories and models. Recent extensions of the FLMP are described in this article along with empirical applications and verification, and progress in the study of speech perception by ear and eye is reviewed within this general theoretical framework. The model illuminates the differences that are observed across different languages in terms of information as opposed to information-processing. Pattern recognition of bimodal speech is representative of pattern recognition in a variety of other domains, such as emotion perception, and there are several domain-dependent reasons why multimodal presentation of audible and visible speech is particularly conducive to accurate pattern recognition. We believe that the positive outcome of this research provides a framework for the development of computer-animated agents, which can serve as language tutors and as conversational characters in other domains, easing the interaction of humans and machines.

Journal Article↗

PubMed2000

The balance of storage and computation in morphological processing: the role of word formation type, affixal homonymy, and productivity.

This article is concerned with the way in which the balance of storage-storing and processing words through full-form representations-and computation-storing and processing words through morpheme-based representations-in lexical processing in the visual modality is affected by the following 3 factors: word formation type (roughly, inflection vs. derivation), productivity, and affixal homonymy. Experimental results for 5 different Dutch suffixes, combined with previous results obtained for 4 comparable Finnish suffixes (R. Bertram, M. Laine, & K. Karvinen, 1999) and 2 Dutch suffixes (R. H. Baayen, T. Dijkstra, & R. Schreuder, 1997), show that none of these factors in isolation is a reliable cross-linguistic predictor of the balance of storage and computation. The authors offer a general framework that outlines how morphological processing is influenced by the interaction of word formation type, productivity, and affixal homonymy.

Adult↗

PubMed2000

Hartree-fock approximation for inverse many-body problems

A new method is presented to reconstruct the potential of a quantum mechanical many-body system from observational data, combining a nonparametric Bayesian approach with a Hartree-Fock approximation. A priori information is implemented as a stochastic process, defined on the space of potentials. The method is computationally feasible and provides a general framework to treat inverse problems for quantum mechanical many-body systems.

Journal Article↗

PubMed1986

Role of electrical interactions in synchronization of epileptiform bursts.

Four general mechanisms can hypothetically contribute to or mediate localized synchronization of neuronal activity: (a) recurrent excitatory chemical synapses, (b) electrotonic coupling via gap junctions, (c) electrical field effects (ephaptic interactions), and (d) changes in the concentration of extracellular ions (e.g., K+). It has generally been believed that synchronization of epileptiform bursts derives primarily, if not exclusively, from recurrent excitatory chemical synapses. Dual intracellular recordings from the CA3 area of the hippocampus have been used to demonstrate the existence of recurrent synaptic excitation, and computer simulations have provided a theoretical framework for the idea that relatively sparse interactions through recurrent excitatory chemical synapses can generate synchronized bursting after inhibitory pathways are blocked with convulsant agents. Additional experimental studies have supported the hypothesis that a model for seizure discharge, the penicillin-induced paroxysmal depolarization shift (PDS), is associated with a large increase in excitatory synaptic conductance. However, recent studies have suggested that electrical interactions are also likely to play an important role in spike synchronization during epileptic discharges. Several research groups have used in vitro preparations to show that afterdischarges and spontaneous bursts of population spikes (which represent synchronized action potentials) can occur after chemical synaptic transmission has been blocked in solutions containing low [Ca2+]. Although this result was first observed in the CA1 area, it has recently been confirmed in other regions of the hippocampus. These experiments indicate that mechanisms other than chemical synaptic transmission are capable of synchronizing action potentials in the hippocampus. In this chapter, two forms of electrical interaction that could mediate synchronization will be considered: (a) electrotonic coupling through gap junctions and (b) electrical field effects through extracellular space. Changes in the concentration of extracellular ions are another mechanism not involving chemical synapses. However, it seems unlikely that ionic changes act on the rapid time scale of electrical interactions, and their contribution is discussed elsewhere in this volume. We review evidence for the existence of electrotonic coupling and electrical field effects in the hippocampus and neocortex, and discuss their possible involvement in the synchronization of epileptiform events.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1998

A software architecture to support a large-scale, multi-tier clinical information system.

A robust software architecture is necessary to support a large-scale multi-tier clinical information system. This paper describes our mechanism for enterprise distribution of applications and support files, the consolidation of data-access functions and system utilities stored on the data access tier, and an application framework which implements a coherent clinical computing environment. The software architecture and systems described in this paper have been robust through pilot testing of our applications at Massachusetts General Hospital.

Computer Security↗

PubMed1999

The hydraulic system of trees: theoretical framework and numerical simulation

Empirical studies pose the problem of the physiological integration of the tree organism, which is also important on the scale of ecosystems. Recently, spatially distributed models emerged, which approach this problem by reflecting the close linkage between physiological processes and the structures of trees and tree stands. In the case of water flow, the tree organism can be regarded as hydraulic system and the branched tree architecture as hydraulic network. Previous models of the hydraulic system either did not take into account the network structure, or they had shortcomings regarding the translation of the underlying physiological assumptions by the discrete computation method. We have developed a theoretical framework which takes the form of a numerical simulation model of tree water flow. A discrete initial boundary value problem (IBVP) combines the phenomena of Darcy flow, water storage and conductivity losses in the hydraulic network. The software HYDRA computes the solution of the IBVP. The theoretical derivation and model tests corroborate the consistent translation of the physiological assumptions by the computational method. Simulation studies enabled us to formulate hypotheses on the following points: (1) differences in the hydraulic segmentation between Picea abies and Thuja occidentalis, (2) responses of the hydraulic system to rapid transpiration changes and to a scenario of drought stress, and (3) how these responses depend on architectural quantities of the trees. The simulation studies demonstrated our possibilities of deriving theoretically well-founded hypotheses about the functioning of the hydraulic system and its relation to system structure. The numerical simulation model is designed as a tool for structure-function studies, which is able to treat tree architecture as independent variable. The model supports the integration of data on tree level, and it can be used for computer experiments which quantify the dynamics of the hydraulic system according to the concepts of system theory. Copyright 1999 Academic Press.

Journal Article↗

PubMed1995

Disulfide stabilization of antibody Fv: computer predictions and experimental evaluation.

Using molecular modeling technology we have recently identified positions in conserved framework regions of Fvs which can be used to stabilize antibody Fvs by an interchain disulfide bond engineered in between the structurally conserved framework positions of the variable domains of heavy (VH) and light (VL) immunoglobulin chains (disulfide-stabilized Fv; dsFv). The computer model indicated the existence of other potential sites in the framework regions that might be suitable for disulfide bond formation between VH and VL. The possibility of obtaining dsFvs using these positions is evaluated here experimentally by constructing dsFv immunotoxins in which the Fv moiety is fused to a truncated form of Pseudomonas exotoxin. We analyzed the extent of dsFv formation and the activity of the resulting dsFv immunotoxins, and compared various dsFv molecules with the scFv immunotoxin. Our results demonstrate that position H44-L105 is the only one which gives high production yields of active dsFv. All other positions gave either low yields and activity or completely failed to produce active dsFv. With one exception, the formation and activities of the dsFvs corresponded to the C alpha-C alpha distance between the VH and VL positions, with an optimal distance of 5.7 A producing the best dsFv. Distances of 6.0-6.9 A resulted in a low yield of protein that was still capable of binding antigen, whereas distances > 7.0 A resulted in molecules in which dsFv formation was not obtained.

Amino Acid Sequence↗

PubMed2000

"Computer addiction": a critical consideration.

Problems related to intemperate Internet use are examined within the conceptual framework of addiction. It is argued that empirical support for the construct validity of computer addiction has yet to emerge, that defining the construct as a unique psychiatric disorder is therefore premature, and that, in most cases, excessive computer use may be symptomatic of other, more primary disorders. Greater caution and rigor are urged in investigating and treating problems related to intemperate computer use.

Behavior, Addictive↗

PubMed1996

Toward a model for nursing informatics.

PURPOSE: To propose a new model for the development of nursing informatics based on historical precedent. SIGNIFICANCE: Nursing informatics is expanding rapidly. The proposed model aids in understanding the areas of research, relating them to each other, and it shows areas where work is missing or should be extended. ORGANIZING FRAMEWORK: Nursing informatics as the interaction of cognitive science, computer science, and information science resting on a base of nursing science. IMPLICATIONS: As this model is tested, it can act as an organizing framework to understand and relate studies of nursing informatics and give organization for future research, education, and development.

Computer Communication Networks↗

PubMed1995

Protein docking combining symbolic descriptions of molecular surfaces and grid-based scoring functions.

With the growing number of known 3D protein structures, computing systems, that can predict where two protein molecules interact with each other is becoming of increasing interest. A system is presented, integrating preprocessing like the computation of molecular surfaces, segmentation, and searching for complementarity in the general framework of a pattern analyzing semantic network (ERNEST). The score of coarse symbolic computations is used by the problem independent control strategy of ERNEST to guide a more detailed analysis considering steric clash and judgements based on grid-based surface representations. Successful examples of the docking system are discussed that compare well with other approaches.

Binding Sites↗

PubMed1993

A constraint logic programming framework for constructing DNA restriction maps.

Restriction mapping is an important computational problem in molecular biology, particularly in genetic engineering and DNA sequencing. It is different in that it is not only a purely computational problem but involves an interaction between experimental data collection procedures and the mapping algorithms. Consequently, the problem is loosely defined and in practice requires a flexible and versatile algorithm. We describe a framework for solving many restriction mapping problems in the constraint logic programming language CLP (R) which takes advantage of the declarative and powerful features of constraint logic programming. A CLP (R) algorithm is developed for solving a simple restriction mapping problem. The algorithm is the extended to handle more complex variations of restriction mapping such as fragments with errors, circular maps, multiple enzymes and partial digests. The mapping variants are integrated within the same framework and differ in the constraints required to define the kind of map consistency. Various search heuristics and control strategies to improve the search process are also incorporated as constraints.

Algorithms↗

PubMed1997

Fit of implant frameworks fabricated by different techniques.

PURPOSE: This study evaluated the precision of fit between an implant framework and a patient simulation model that consisted of five implant abutments located in the mandibular symphysis area. One-piece cast frameworks were compared with Procera machined and laser-welded frameworks with laser videography. MATERIAL AND METHODS: Five frameworks of each type were measured with a laser digitizer and a graphics computer program to determine a single point represented as the "Centroid" for each framework component and each implant abutment. Differences between the paired centroids for each framework/abutment interface are reported as x- and y-axis displacements, and z-axis gaps. The direction of the x- and y-axis displacements was determined. RESULTS: There were significant differences (p < 0.05) in the precision of fit between both the one-piece cast frameworks and the Procera frameworks, when compared with the abutments in the patient simulation model. The laser-welded framework exhibited a more precise fit than the one-piece casting, with significant differences at four of the five prosthodontic interfaces, when evaluated by the mean z-axis gap at the centroid points.

Computer Graphics↗

PubMedDate not supplied

Graph automorphism perception algorithms in computer-enhanced structure elucidation.

The concept of graph symmetry is explained in terms of the vertex automorphism group, which is a subgroup of the complete vertex permutation group. The automorphism group can be deduced from the automorphism partition of graph vertices. An algorithm is described which constructs the automorphism group of a graph from the automorphism vertex partitioning. The algorithm is useful especially for graphs which contain more than one vertex-partition set. Several well-known topological symmetry perception algorithms that yield automorphism partitions are compared. The comparison is favorable to the Shelley-Munk algorithm, developed in the framework of the SESAMI system for computer-enhanced structure elucidation.

Algorithms↗

PubMed1994

A humanized antibody specific for the platelet integrin gpIIb/IIIa.

C4G1, a murine mAb reactive with the platelet gpIIb/IIIa integrin, was humanized for potential treatment of thrombosis-related disorders. The variable regions of light- and heavy-chain cDNAs from the C4G1 hybridoma were first cloned and sequenced. Humanized C4G1 Ab of the IgG1 isotype was constructed by combining the complementarity-determining regions of C4G1 with human framework and constant regions. The human framework was chosen to maximize homology with the C4G1 variable region sequence, and a computer model of C4G1 was used to aid design of the final framework sequence. Genetic constructs were also developed to produce Fab and F(ab')2 fragments of the humanized C4G1 Ab. The humanized IgG1 Ab as well as the Fab and F(ab')2 fragments showed equivalent binding affinities to their murine counterparts, indicating no loss in binding affinity during the humanization process. The humanized Ab and its fragments were also shown to inhibit platelet aggregation and to inhibit binding of fibrinogen to gpIIb/IIIa in vitro.

Amino Acid Sequence↗

PubMed1998

Computer modelling of spinal cord stimulation and its contribution to therapeutic efficacy.

An overview of computer models developed since the late seventies, which enable the simulation of the primary effects of spinal cord stimulation (SCS) on nerve fibres, is presented. These models consist of a 3-dimensional volume conductor model, representing anatomical structures and their electrical conductivities, and cable models representing the electrical behaviour of nerve fibres. The characteristics of these models and their relation to anatomy and physiology, as well as the calculation of stimulation-induced electrical fields and their effect on nerve fibre models, are reviewed. It is shown that most characteristics of SCS as predicted by computer modelling correspond well with empirical data. Accordingly, a theoretical framework describing the relations between relevant parameters in SCS is presented. Finally, it is shown how theory and computer modeling are applied to improve the efficacy of SCS by the optimization of its technique, primarily by the design of new epidural electrodes.

Computer Simulation↗

PubMed2026

Secure bioinformatics: privacy-preserving federated analytics using homomorphic encryption.

MOTIVATION: Large-scale bioinformatics analyses increasingly require collaboration across multiple cohorts and institutions, yet existing workflows often rely on data co-localization, which is slow, difficult to scale, and raises privacy concerns. We present a privacy-preserving federated analytics framework that enables secure statistical analysis across distributed datasets without transferring raw data, by performing all computations on encrypted data via cryptographic methods. RESULTS: We evaluate the framework by validating polygenic risk scores and conducting meta-analyses on two real-world cohorts. The proposed solution achieves over 99.9% accuracy relative to plaintext analyses, while maintaining scalable runtime performance with increasing data size and number of participating sites. These results demonstrate the feasibility of secure federated analytics for practical bioinformatics applications involving sensitive data.

Computational Biology↗