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A biological marker model for predicting disease transitions.

For patients with chronic myelogenous leukemia (CML), the effect of elevated blood levels of adenosine deaminase (ADA) is studied as a marker for transitions from stable disease to blast crisis and then to death. Data in the form of snapshots over time, with day, state of disease, and ADA level, are analyzed for 55 patients. A simple three-state Markov model with one-way transition probabilities dependent on ADA is used to determine if the marker has a significant effect on the prediction of changes from stable disease to blast crisis.

Adenosine Deaminase↗

[Occupational aging (biological age modeling)].

Based on workers' biologic age, the authors created a systemic model of general and occupational ablebodiedness and tested the model on selective determination of biologic age among workers of various Ukrainian regions. The results proved increase in occupational aging of the population. General and occupational ablebodiedness in males of the select was lower than that in the females. Occupational ablebodiedness of population, especially of males, is considerably decreased. The latter evidence is a function of economic circumstances: heavy, hazardous and dangerous work conditions hardly compensated by payments.

Adult↗

Distributing working versions of published mathematical models for biological systems via the Internet.

Mathematical models are useful tools for investigating complex systems. By representing physiological systems as models, theories can be tested quantitatively against data from the system. Models can be used to explore new theories prior to experimentation and to design studies to optimize experimental resources. They can also be used as teaching tools to illustrate physiochemical principles. In spite of their usefulness and the time invested in developing models, published models are often underused due to the difficulty in obtaining working versions of the model. To address this problem we have designed a library for mathematical models of biological systems on the Internet. The library contains published models of biological systems in formats compatible with several modeling packages, from the fields of physiology, metabolism, endocrinology, biochemistry, and chemistry. The models can be viewed graphically, model solutions can be viewed as plots against data, and models can be downloaded to be run with software on the user's own system. The address of the library is: http://biomodel.georgetown.edu/model/ Investigators are invited to submit working versions of published models to the library. Models can be submitted electronically at the time a manuscript is accepted for publication. As journals go online, articles containing models can be linked to working versions of the models in the library. By increasing access to working versions of models, more of the investment in kinetic studies and model development can be realized.

Computer Simulation↗

Histologic evaluation of periodontal implants in a biologically "closed" model.

To study the biologic response, three commercial calcium phosphate implant materials (Calcitite, Periograf, Synthograft) were implanted in cuspid root "windows" in four beagle dogs. No implant material was placed in the fourth cuspid window which served as a control. Following mucoperiosteal flap elevation, windows were chiseled in bone to the root surface which allowed implant particles to contact bone, fibrous connective tissue, cementum and dentin without exposure to the oral environment. Animals were sacrificed after 1, 3, 5 and 6 months. Histologically, all implant materials were well tolerated. At 1 month, implant particles were surrounded by fibrous tissue. Fibrous tissues filled the control defect. At 3 months, implant sites exhibited partial bony repair with connective tissue surrounding implant particles. A ring of osteoid surrounded Synthograft particles. Control defect repair was complete. At 5 and 6 months, implant sites exhibited advanced, though incomplete, bony repair. New bone encompassed the Synthograft particles. It was concluded: Control sites healed most rapidly. Calcitite and Periograft were well tolerated space occupiers. Synthograft was a nidus for bone deposition.

Alveolar Process↗

Simple stochastic fingerprints towards mathematical modeling in biology and medicine. 3. Ocular irritability classification model.

MARCH-INSIDE methodology and a statistical classification method--linear discriminant analysis (LDA)--is proposed as an alternative method to the Draize eye irritation test. This methodology has been successfully applied to a set of 46 neutral organic chemicals, which have been defined as ocular irritant or nonirritant. The model allow to categorize correctly 37 out of 46 compounds, showing an accuracy of 80.46%. Specifically, this model demonstrates the existence of a good categorization average of 91.67 and 76.47% for irritant and nonirritant compounds, respectively. Validation of the model was carried out using two cross-validation tools: Leave-one-out (LOO) and leave-group-out (LGO), showing a global predictability of the model of 71.7 and 70%, respectively. The average of coincidence of the predictions between leave-one-out/leave-group-out studies and train set were 91.3% (42 out of 46 cases)/89.1% (41 out of 46 cases) proving the robustness of the model obtained. Ocular irritancy distribution diagram is carried out in order to determine the intervals of the property where the probability of finding an irritant compound is maximal relating to the choice of find a false nonirritant one. It seems that, until today, the present model may be the first predictive linear discriminant equation able to discriminate between eye irritant and nonirritant chemicals.

Algorithms↗

A nonlocal continuum model for biological aggregation.

We construct a continuum model for biological aggregations in which individuals experience long-range social attraction and short-range dispersal. For the case of one spatial dimension, we study the steady states analytically and numerically. There exist strongly nonlinear states with compact support and steep edges that correspond to localized biological aggregations, or clumps. These steady-state clumps are reached through a dynamic coarsening process. In the limit of large population size, the clumps approach a constant density swarm with abrupt edges. We use energy arguments to understand the nonlinear selection of clump solutions, and to predict the internal density in the large population limit. The energy result holds in higher dimensions as well, and is demonstrated via numerical simulations in two dimensions.

Algorithms↗

EM field prediction inside lossy multilayer elliptic cylinders for biological-body modeling and numerical-procedure testing.

In this paper, a biological model made up of a multilayer elliptic cylinder is considered. This canonical scattering problem is solved by a recursive procedure, which has been generalized to the case of lossy materials by using the analytical properties of Mathieu functions. Although it is a simplified model, this stratified configuration may simulate better than circular cylinders the local behavior of biological subsystems. In addition, it represents an effective tool for producing analytical data for testing direct-scattering numerical codes in biomedical applications and for the evaluation of reconstruction procedures in medical imaging.

Animals↗

Formaldehyde fixation of cGMP in distinct cellular pools and their recognition by different cGMP-antisera. An immunocytochemical study into the problem of serum specificity.

Three different antisera raised against the same formaldehyde fixed cGMP conjugate were tested for their specificity in two non-biological and two biological model systems. The first non-biological model system was based on nucleotides fixed to gelatin by formaldehyde and the other non-biological model was nitrocellulose paper as a carrier for nucleotides coupled to proteins by formaldehyde. All antisera proved specific for cGMP in both models. As biological models we used the in vitro incubated hippocampus slice and the in vitro incubated aortic ring. In hippocampus slices all three antisera showed cGMP-producing cells after atrial natriuretic factor stimulation. However, there were significant differences in the visualization of cGMP-immunoreactivity between the three antisera when sodium nitroprusside or potassium were used to stimulate cGMP production. Nevertheless, these differential staining patterns all showed cGMP-immunoreactivity using the conventional immunocytochemical control tests. In the aorta ring all three antisera showed the same strong increase in cGMP-immunoreactivity after in vitro stimulation with sodium nitroprusside. These results were corroborated by biochemical assay of cGMP. We conclude that these three antisera all demonstrate cGMP-immunoreactivity in the biological models used. The different staining patterns that occur are caused by differences in the microchemical milieu of the formaldehyde-fixed cGMP. The use of different antibodies to cGMP may give information about this microchemical milieu which may eventually contribute to a better understanding of different intracellular cGMP pools.

Animals↗

Variation of efficiency with free-energy dissipation in models of biological energy transduction.

For two models of biological free-energy transducers, it is investigated how free-energy dissipation and efficiency vary as (i) the demand for output free energy, (ii) the input free energy or (iii) the properties of the transducers themselves, are varied. One model is representative of near-equilibrium free-energy transducers in general, the other is a special case of far-from-equilibrium free-energy transduction, reminiscent of proton pumping by bacteriorhodopsin. It turns out that the relationship between efficiency and free-energy dissipation depends strongly on what varies. In some cases, free-energy dissipation increases as the efficiency increases. It is suggested that this is one reason why biological evolution has not resulted in high efficiencies and low rates of free-energy dissipation. For the near-equilibrium free-energy transducer, the free-energy dissipation at the static head steady state is minimal with respect to variations in the output force. For the far-from-equilibrium model (of bacteriorhodopsin), the static head does not correspond to such a minimum, if that free-energy transducer slips.

Bacteriorhodopsins↗

Defining the relationship of oxygen delivery and consumption: use of biologic system models.

To determine the most appropriate mathematical description of the relationship between oxygen consumption and oxygen delivery, we compared the statistical validity of a piecewise linear model to two different biologic system models--Michaelis-Menten (MM) kinetics (used for enzyme systems) and the exponential dose-response relationship (used to describe drug administration and induced response). Nine rabbits underwent five incremental steps of normovolemic hemodilution to progressively decrease DO2. VO2 was measured concurrently by a metabolic gas monitor. All three models (piecewise linear, Michaelis-Menten, and exponential) provided a very close population curve fit to the data points (r2 = 0.88, 0.91, and 0.92). However, there were significant differences in maximum predicted VO2 (VO2max)--6.8, 9.9, 7.2 ml O2.kg-1.min-1 (P < 0.0002)--and a wide range in the model-specific parameters for individual rabbits (critical DO2 6.5-11.8 ml O2.kg-1.min-1, Km 4.2-11.4 ml O2.kg-1.min-1, and kappa 0.12-0.23 ml O2-1.kg.min). In the curvilinear models, average and population parameters were not significantly different. However, in the piecewise linear model, population critical DO2 (10.9 ml O2.kg-1.min-1) was 30% more than the average critical DO2 (8.4 ml O2.kg-1.min-1) for the nine rabbits (P < 0.005). VO2max values predicted by the piecewise linear and exponential dose-response model were more consistent with those in previous publications than was the higher VO2max predicted by the MM model. The difference in the average versus population critical DO2 in the piecewise linear model meant that population modeling was inaccurate because it yielded a critical DO2 higher than that demonstrated by eight of nine individual rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗