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Biomedical subjects

D Beeman

Publications and source records attributed to D Beeman.

10 recordsLinked to original sources

Towards NeuroML: model description methods for collaborative modelling in neuroscience.

Biological nervous systems and the mechanisms underlying their operation exhibit astonishing complexity. Computational models of these systems have been correspondingly complex. As these models become ever more sophisticated, they become increasingly difficult to define, comprehend, manage and communicate. Consequently, for scientific understanding of biological nervous systems to progress, it is crucial for modellers to have software tools that support discussion, development and exchange of computational models. We describe methodologies that focus on these tasks, improving the ability of neuroscientists to engage in the modelling process. We report our findings on the requirements for these tools and discuss the use of declarative forms of model description--equivalent to object-oriented classes and database schema--which we call templates. We introduce NeuroML, a mark-up language for the neurosciences which is defined syntactically using templates, and its specific component intended as a common format for communication between modelling-related tools. Finally, we propose a template hierarchy for this modelling component of NeuroML, sufficient for describing models ranging in structural levels from neuron cell membranes to neural networks. These templates support both a framework for user-level interaction with models, and a high-performance framework for efficient simulation of the models.

Animals↗

Kinetic properties of glucosyltransferase adsorbed onto saliva-coated hydroxyapatite.

Results from previous studies have shown that several properties of glucosyltransferase (GTF) adsorbed onto saliva-coated hydroxyapatite beads differ from those of GTF in solution. For example: thermostability, pH-activity dependency, sensitivity to inhibitors. The aim of this study was to compare the kinetics of the adsorbed GTF with its kinetic properties in solution. Hydroxyapatite beads were coated with human parotid saliva (sHA). Following washes, cell-free GTF enzyme from Streptococcus sobrinus 6715 (S. sobrinus 6715) or Streptococcus mutans GS-5 (S. mutans GS-5) was adsorbed onto sHA. The GTF-coated sHA were then incubated with radiolabeled sucrose for intervals of 5-360 minutes and the amount of glucans synthesized in situ by the adsorbed GTF was determined and compared with that produced in solution. The adsorbed GTF (from S. sobrinus 6715) exhibited a sharp increase in glucan production within the first 5 minutes of incubation while surface-bound GTF of S. mutans GS-5 displayed an initial burst of activity within the first 15 minutes of incubation. During the next 6 hours (duration of experiment) the amount of glucan on the beads did not increase with either enzyme. In contrast, the kinetic profile of the two GTFs in solution demonstrated a linear increase in the amount of glucans formed, with no initial burst effect. The results indicate that the rapid formation of glucans by GTF adsorbed onto sHA could have implications for colonization by oral microorganisms on tooth surfaces. The accelerated synthesis of glucan on tooth surfaces may affect the microbiology of the dental plaque, and might also influence the movement of substances, such as acids and antiplaque agents, across the acquired pellicle and dental plaque.

Adsorption↗

The effect of delmopinol on glucosyltransferase adsorbed on to saliva-coated hydroxyapatite.

The aim was to explore the effects of delmopinol, a substituted amino-alcohol compound recently reported as a potential antiplaque agent, on GTF activity in solution and when adsorbed on to sHA. Delmopinol was without a significant effect on GTF activity in solution. In contrast, a reduction in the bound glucans synthesized by the adsorbed GTF was found in the presence of delmopinol. Delmopinol did not displace the adsorbed GTF from the sHA, nor was there significant desorption of glucans from sHA. The total glucan synthesis (bound and unbound) was reduced in the presence of delmopinol. Inhibition of GTF was not reversed by sucrose. Inhibition of GTF activity by delmopinol apparently results from drug-enzyme interaction on the surface of sHA beads. These observations provide further support for the important differences in the properties of adsorbed GTF and GTF in solution, illustrating that GTF-drug interaction differs between enzyme adsorbed to surfaces and enzyme in solution.

Adsorption↗

Interactions of delmopinol with constituents of experimental pellicle.

The prolonged retention of an effective chemotherapeutic agent on oral surfaces and in dental plaque aids in plaque control. The objective of this study was to investigate interactions between delmopinol, a morpholinoethanol derivative, and experimental pellicle. Hydroxyapatite beads were coated with different constituents of pellicle (e.g., saliva, carbohydrates, cell-free enzymes, and bacteria). Delmopinol demonstrated a higher affinity for saliva-coated hydroxyapatite (sHA) and for experimental pellicle coated with in situ-synthesized glucans than for untreated hydroxyapatite. High-molecular-weight (MW) dextran but not low-MW dextran interfered with the adsorption of delmopinol to sHA. Delmopinol did not compete with dextran for the same binding sites on sHA, nor did it compete with saliva for the same binding sites on untreated hydroxyapatite. Delmopinol inhibited the activity of cell-free fructosyltransferase adsorbed onto sHA. In addition, synthesis of glucans by Streptococcus mutans adsorbed onto sHA was significantly reduced in the presence of delmopinol.

Adsorption↗

Role of a cell surface-associated protein in adherence and dental caries.

Insertional inactivation of the Streptococcus mutans spaP gene was used to construct an isogenic mutant (834) of strain NG8 (serotype c) which lacked the major cell surface-associated protein referred to as P1 (15). Results of several studies suggest that P1 is involved in the adherence of S. mutans to saliva-coated apatite surfaces. With an in vitro model system of hydroxyapatite (HA) beads coated with parotid saliva (PS) and additional HA surfaces coated with PS and in situ-formed glucan, it was observed that mutant 834 adhered poorly to the PS/HA surfaces. In contrast, both parent and mutant strains bound to the PS-glucan/HA surface. Groups of intact and desalivated rats were infected with each strain to determine relative capacities to induce dental caries. Rats were fed a highly cariogenic diet containing 56% sucrose for 3 to 5 weeks. Each strain colonized the rodent model and caused similar levels of smooth-surface caries under these dietary conditions. It was concluded that P1 influences the ability of organisms to adhere to saliva-coated surfaces and possibly affects primary colonization of the oral cavity in the absence of a glucan surface but has no effect on glucan-mediated adherence in vitro or in vivo.

Animals↗

Development of an immunization tracking system in a large health maintenance organization. Group Health Cooperative of Puget Sound.

We have successfully developed a mainframe system for tracking all immunizations administered to enrollees in a large HMO. This system will provide comprehensive immunization records on a population of over 350,000 patients. Data required by the National Childhood Vaccine Injury Act of 1986 are locally entered into terminals, and records of immunization are stored in a database. Preliminary results show that data entry times are practical, but that improvement in data quality is needed. This immunization tracking system will be used for research, and as the foundation of an immunization reminder system under development.

Health Maintenance Organizations↗

Teaching interactive signing in a dialogue situation to mentally retarded individuals.

Verbal prompts, modeling, physical guidance, positive reinforcement, fading, and chaining procedures were used to teach two nonverbal individuals, one severely and one moderately mentally retarded, an interactive signing dialogue in a naturalistic snack time setting. Both were required to initiate signed communication and to respond to signed communication with either action or manual signing. Using a multiple probe design across three dialogue situations, each client was successively taught his role in each dialogue with a staff member serving as his partner. After both trainees had mastered a dialogue role, signing competency was formally probed as they interacted with their staff partner in a maintenance situation and with the other trainee in a generalization situation. Results showed that clients could learn to use signed communication in each dialogue situation but that extensive training was required. Data also indicated that only partial generalization to the client-client situation occurred.

Adolescent↗

Development and validation of an immunization tracking system in a large health maintenance organization.

Practitioners seeing individual patients and those charged with improving immunization practices in that population need accurate information on the epidemiology of immunizations within the population. To meet this need, we have developed a computer-based record of data required by the National Childhood Vaccine Injury Act of 1986 for all immunizations given to 350,000 enrollees in a large health maintenance organization. In the first eight months of operation, 102,271 immunizations representing 11 separate antigens given to 65,676 enrollees were entered into the database. Comparison of immunizations given and recorded in the medical record with the database shows that the system has high sensitivity, specificity, and positive predictive value, but a relatively low negative predictive value. The database is being used for analysis of current immunization practices for Haemophilus influenzae b vaccine and for research on adverse outcomes of childhood immunizations.

Databases, Factual↗