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At least 991 records · Page 55Linked to original sources
PubMed2000

A fuzzy logic model of fracture healing.

A quantitative biomechanical model describes the tissue transformation during healing of a transverse osteotomy of a sheep metatarsal. The model predicts bridging of the bone ends through cartilage, followed by the growth of a callus cuff, and finally, the resorption of callus after ossification of the interfragmentary gap. We suggest bone density or the modulus of elasticity do not sufficiently characterize healing tissue for predictive purposes. In addition to the stimulus reflected by strain energy density we introduce a new osteogenic factor based upon stress gradients and which predicts areas of a high osteogenic capacity. Our model distinguishes three basic types of tissue, namely bone, cartilage and fibrous tissue. A fuzzy controller is proposed to model the tissue reaction. A set of fuzzy rules derived from medical knowledge has been implemented to describe tissue transformation such as intramembraneous or chondral ossification, atrophy or destruction. Fuzzy logic is able to model tissue transformation processes within the numerical simulation of remodeling processes. This approach improves the simulation tools and affords the potential to optimize planning of animal experiments and conduct parametric studies.

Algorithms↗
PubMed1988

Electron microscopic studies of free and proteinase-bound duck ovostatins (ovomacroglobulins). Model of ovostatin structure and its transformation upon proteolysis.

Conformational changes of duck ovostatin (ovomacroglobulin) upon complexing with thermolysin have been studied by electron microscopy. Both free and thermolysin-bound ovostatin preparations were negatively stained with uranyl acetate, a series of three pictures were taken at 10 degrees specimen tilt intervals (+10 degrees, 0 degrees, and -10 degrees), and images of the inhibitor molecules were observed in three dimensions. Four approximately cylindrical subunits were observed in free ovostatin. Two subunits associated approximately midway from both ends to form a dimer of four arms. Two dimers associated with each other at the midpoint to form a tetramer. The proteinase susceptible "bait" regions were located near the center of the molecule. Eight arms of the tetramer take various configurations. The orthogonal extent of free tetrameric ovostatin in a two-dimensional micrograph averages 26.0 +/- 4.7 x 34.0 +/- 5.0 nm. Upon complexing with thermolysin, all eight arms curl toward the center of the molecule, having four arms upward and the other four downward. Thus, proteinase-bound ovostatin has a uniform structure with a 2-fold axis of symmetry. The overall structure of the complex is more compact with average dimensions of 16.9 +/- 0.6 x 16.9 +/- 0.6 x 19.9 +/- 0.4 nm. From these electron microscopic studies we propose that a proteinase reaches to the center of the free ovostatin molecule and attacks the bait region. Subsequent to proteolysis the subunit arms curl and entrap the enzyme within the ovostatin molecule. The results support the unique mechanism of inhibition of proteinases by alpha 2-macroglobulin and ovostatin postulated from biochemical observations (Barrett, A. J., and Starkey, P. M. (1973) Biochem. J. 133, 709-724; Nagase, H., and Harris, E. D., Jr. (1983) J. Biol. Chem. 258, 7490-7498).

Algorithms↗
PubMed1999

[Establishment of hepatitis C virus reproductive model of human peripheral blood mononuclear cells transformed by Epstein-Barr virus].

OBJECTIVE: For the present, one of the crucial questions to study pathogenic mechanism of hepatitis C and its drug therapy is to seek a suitable cell model which may support the replication of hepatitis C virus(HCV). In this article, we made effort on the study of this aspect. METHODS: Using Epstein-Barr virus(EBV), we transformed the peripheral blood mononuclear cells(PBMC) isolated from a patient diagnosed as chronic hepatitis C. HCV RNA from the cultured cells and the supernatants were analysed by reverse transcriptase-polymerase chain reaction(RT-PCR) at an intervals of one month. RESULTS: HCV positive-strand RNA could be detected continually in the cultured cells for more than one year since the establishment of the transformed PBMC clone whereas the negative-strand RNA were also observed in the cultured cells. Interestingly, the HCV positive-strand RNA could be identified in supernatants intermittently. CONCLUSION: HCV may exist in the cultured cell line for a longer period and reproduce in and secrete out of the cells. This will offer a new cell model for studying the molecular biology and immunology of HCV.

Cell Transformation, Viral↗
PubMed1988

Real-time models of morphogenetic processes.

Morphological transformations are often describable by simple series kinetic models, A----B, A----B----C, etc., which allow assessment of the rates of interconversion of the distinguishable shapes or forms present and their probabilities of occurrence at various points in time, thus providing a means for kinetic comparisons with biochemical measurements of the molecular-level reactions that cause the transformations. When changes in cell morphology are followed turbidimetrically, the real-time progress curves can be simulated by fitting the data to a form of Beer's law for scattering by mixtures in which the species concentrations change with time in accordance with the chosen kinetic scheme. Because many even relatively large cells are mostly water, classical light scattering theory can be used to interpret the turbidimetric data in terms of simple geometrical models of average cell size and shape suggested by microscopic examination. Two examples are briefly considered, the stimulus-induced changes in blood platelet shape and apparent size and their correlation with cytosolic-free calcium, and apparent swimming motion exhibited by neutrophils in suspension.

Blood Platelets↗
PubMed1996

Conformation of a water-soluble beta-sheet model peptide. A circular dichroism and Fourier-transform infrared spectroscopic study of double D-amino acid replacements.

Among peptide secondary structures beta-sheet domains have been much less intensively studied than alpha-helical conformations, mainly because of the lack of well characterized model peptides. In the present paper the secondary structure of a water-soluble de novo peptide consisting of 26 amino acids (DPKGDPKGVTVTVTVTVTGKGDPKPD-NH2) and the corresponding double D-amino acid replacement set have been studied by circular dichroism and Fourier-transform infrared spectroscopy. The model peptide was found to be unstructured in aqueous solution at peptide concentrations < 10(-3) mol/L but to adopt a predominantly beta-sheet structure in the presence of 15 mM sodium dodecyl sulfate or at apolar/water interfaces. Although the peptide is composed of amino acids with low helical propensity, it formed a single-stranded helical structure in aqueous trifluoroethanol. The D-amino acid replacement set was synthesized in order to study the conformational stability of the model peptide selectively in distinct regions. The data show that both the alpha-helix present in 50% trifluoroethanol as well as the beta-sheet domain formed in the presence of sodium dodecyl sulfate or at apolar/water interfaces, are located in the region between Val9 and Thr18. Pairwise substitution of adjacent amino acids by their corresponding D-amino acids provides a pronounced beta-sheet disturbance. These findings demonstrate that double D-amino acid replacements may be used to locate beta-sheet domains in peptides.

Amino Acid Sequence↗
PubMed1997

Modelling accelerated degradation data using Wiener diffusion with a time scale transformation.

Engineering degradation tests allow industry to assess the potential life span of long-life products that do not fail readily under accelerated conditions in life tests. A general statistical model is presented here for performance degradation of an item of equipment. The degradation process in the model is taken to be a Wiener diffusion process with a time scale transformation. The model incorporates Arrhenius extrapolation for high stress testing. The lifetime of an item is defined as the time until performance deteriorates to a specified failure threshold. The model can be used to predict the lifetime of an item or the extent of degradation of an item at a specified future time. Inference methods for the model parameters, based on accelerated degradation test data, are presented. The model and inference methods are illustrated with a case application involving self-regulating heating cables. The paper also discusses a number of practical issues encountered in applications.

Equipment Failure↗
PubMedDate not supplied

Genetic error, sex, and diploidy.

Mathematical models and experiments on transformation are reported testing the hypothesis that sex and diploidy evolved as a DNA repair system. The models focus on the origin of diploidy and sex by studying selection between asexual haploids, sexual haploids, and diploids. Haploid cells are efficient replicators, while diploid cells are resistance to damage. A sexual haploid may combine the advantages of both: spending much of its life cycle in the haploid state, then temporarily fusing to become diploid, followed by splitting to the haploid state. During the diploid state DNA damage can be repaired, since there are two copies of the gene in the cell and one copy is presumed to be undamaged. Five basic rate parameters are employed: birth and death; genomic damage (for the haploids alone); and, for the sexual cell, fusion and splitting. Parameter space bifurcation diagrams for the equilibria are drawn, and solutions of the equations are described in terms of these diagrams. Each type of cell has a region of the parameter space that it occupies exclusively (given its initial presence in the competition). The haploid wins in environments characterized by low damage. The diploid wins in environments characterized by high damage, low mortality, and abundant resources. In general, only a single type of cell occupies a given portion of the space. We find, however, that competitive coexistence of an asexual diploid and sexual haploid is possible in spite of the fact that they are competing for a single resource (nucleotide building blocks). Sex can increase from rarity if matings occur with asexual cells. Only sex can cope with both high mortality and high damage. We then turn to natural bacterial transformation as a model system for the experimental study of sex. Natural transformation in distributed widely, but apparently sparsely, in all bacterial groups. A very preliminary phylogenetic analysis of the bacilli and related species indicates that transformation is probably not a diversifying force in bacterial evolution. However, it is difficult to be sure because of the ambiguity surrounding negative data. Experiments with the bacterium Bacillus subtilis indicate that transformation frequencies respond adaptively to DNA damage if homologous donor DNA is used. Several specific hypotheses for this response are considered. Recent work in other labs on the evolution of transformation is discussed from the point of view of the hypothesis that transformation functions in DNA repair.

DNA Repair↗
PubMed1997

Binding and transport of transforming DNA by Bacillus subtilis: the role of type-IV pilin-like proteins--a review.

The pathway for binding, processing and transport of transforming DNA into competent cells of Bacillus subtilis is described. The known proteins involved in mediating these processes are reviewed in turn, including several that resemble proteins required for type-IV pilus assembly and function, and those involved in protein secretion. Based on the phenotypes of null mutations in the cognate genes for these proteins, on similarities to other proteins and on membrane localization and topology data, proposals are made for the roles of the individual proteins in the transformation process. A dynamic model is suggested for the presentation of transforming DNA to the transport apparatus.

Amino Acid Sequence↗
PubMed1999

Separable contributions of ordered and disordered lipid fatty acyl chain segments to nuCH2 bands in model and biological membranes: a Fourier transform infrared spectroscopic study.

In this article, the assignment of the nu(C-H) stretching region of lipid molecules is revisited. This region is extensively used to follow lipid phase transitions, and especially the frequency shifts and bandwidth alterations in the nu(sym)CH2 band have been utilized in this respect. Here, we propose and prove that behind these phenomena there are pairs of component bands in the cases of both the nu(sym)CH2 and the nu(as)CH2 bands. The lower-frequency components of the pairs are assigned to the vibrations of CH2 groups on trans segments of the fatty acyl chains, while the higher-frequency components of the pairs are assigned to CH2 groups on gauche segments. To prove these assignments, we have shown that the nuCH2 frequencies are characteristic of the conformation of the lipid fatty acyl chain itself, and not the state of the whole lipid matrix. Curve fitting in fact revealed the conformer-specific components. With the use of singular value decomposition analysis we have demonstrated that the relative intensity changes in the components, and not the shifts in the whole bands, cause the observed shifts in the nuCH2 bands upon lipid phase transition. The results of this approach are presented for deuterium-saturated dioleoyl-phosphatidylcholine mixtures, for the gel --> liquid-crystalline phase transition of dipalmitoyl-phosphatidylcholine multilayers, and for a biological membrane, barley thylakoid. This refined assignment offers physically plausible reasoning for the observed phenomena and is able to explain frequency shifts and bandwidth changes observed previously upon lipid phase transitions, including their nonconcerted temperature dependences. In biological membranes, this interpretation allows the separation of protein- and membrane-dynamics-induced lipid conformational changes.

Cell Membrane↗
PubMed2001

Continuing medical education, needs assessment, and program development: theoretical constructs.

Continuing medical education (CME) program development and needs assessment have historically been practiced within the tradition of Ralph Tyler's education model. In light of transformational social, political, economic, and technical forces that demand greater account-ability and responsiveness from physicians, CME units are challenged to transform their cultures and structures from models that deliver education to models that support the facilitation of learning for enhanced competence and performance. This article describes key change forces for physicians and brings program development and needs assessment into focus for the discussion. The impact of change forces on program development and needs assessment are examined, and some techniques to move beyond the traditional approach of felt needs are presented as a way of enabling strategic administrative planning and change management.

Curriculum↗
PubMed2007

Predicting costs over time using Bayesian Markov chain Monte Carlo methods: an application to early inflammatory polyarthritis.

This article focuses on the modelling and prediction of costs due to disease accrued over time, to inform the planning of future services and budgets. It is well documented that the modelling of cost data is often problematic due to the distribution of such data; for example, strongly right skewed with a significant percentage of zero-cost observations. An additional problem associated with modelling costs over time is that cost observations measured on the same individual at different time points will usually be correlated. In this study we compare the performance of four different multilevel/hierarchical models (which allow for both the within-subject and between-subject variability) for analysing healthcare costs in a cohort of individuals with early inflammatory polyarthritis (IP) who were followed-up annually over a 5-year time period from 1990/1991. The hierarchical models fitted included linear regression models and two-part models with log-transformed costs, and two-part model with gamma regression and a log link. The cohort was split into a learning sample, to fit the different models, and a test sample to assess the predictive ability of these models. To obtain predicted costs on the original cost scale (rather than the log-cost scale) two different retransformation factors were applied. All analyses were carried out using Bayesian Markov chain Monte Carlo (MCMC) simulation methods.

Adult↗
PubMed1995

Trends in mortality from melanoma in Canada and prediction of future rates.

A long term increase in incidence of and mortality due to malignant melanoma has been observed in all well documented white populations. The major identified cause of melanoma is sun exposure. One would expect predictions of future atmospheric ozone depletion to lead to an increase in ultraviolet radiation (UVR) and in the effects of sun exposure. We consider age-period data for Canadian malignant malanoma mortality. We fit a multiplicative exponential/logistic (MEL) model to the data and extrapolate to AD 2010 hence yielding point estimates of future rates. We obtain total mortality forecasts by multiplying rates by population estimates. We present standard errors for forecasts. We forecast that melanoma will be a much larger burden on the health care system in the early years of the next century than it is at present. We obtain an age-cohort model by a simple transformation of the age-period model. Also, we obtain unconditional probabilities of death due to melanoma both for age-period and age-cohort models. We discuss the assumptions underlying the MEL model that suggest possible relationships between UVR and melanoma.

Adult↗
PubMed2005

Altered iron homeostasis involvement in arsenite-mediated cell transformation.

Chronic exposure to low doses of arsenite causes transformation of human osteogenic sarcoma (HOS) cells. Although oxidative stress is considered important in arsenite-induced cell transformation, the molecular and cellular mechanisms by which arsenite transforms human cells are still unknown. In the present study, we investigated whether altered iron homeostasis, known to affect cellular oxidative stress, can contribute to the arsenite-mediated cell transformation. Using arsenite-induced HOS cell transformation as a model, it was found that total iron levels are significantly higher in transformed HOS cells in comparison to parental control HOS cells. Under normal iron metabolism conditions, iron homeostasis is tightly controlled by inverse regulation of ferritin and transferrin receptor (TfR) through iron regulatory proteins (IRP). Increased iron levels in arsenite transformed cells should theoretically lead to higher ferritin and lower TfR in these cells than in controls. However, the results showed that both ferritin and TfR are decreased, apparently through two different mechanisms. A lower ferritin level in cytoplasm was due to the decreased mRNA in the arsenite-transformed HOS cells, while the decline in TfR was due to a lowered IRP-binding activity. By challenging cells with iron, it was further established that arsenite-transformed HOS cells are less responsive to iron treatment than control HOS cells, which allows accumulation of iron in the transformed cells, as exemplified by significantly lower ferritin induction. On the other hand, caffeic acid phenethyl ester (CAPE), an antioxidant previously shown to suppress As-mediated cell transformation, prevents As-mediated ferritin depletion. In conclusion, our results suggest that altered iron homeostasis contributes to arsenite-induced oxidative stress and, thus, may be involved in arsenite-mediated cell transformation.

Antioxidants↗
PubMed2001

Demand for health care in Denmark: results of a national sample survey using contingent valuation.

In this paper we use willingness to pay (WTP) to elicit values for private insurance covering treatment for four different health problems. By way of obtaining these values, we test the viability of the contingent valuation method (CVM) and econometric techniques, respectively, as means of eliciting and analysing values from the general public. WTP responses from a Danish national sample survey, which was designed in accordance with existing guidelines, are analysed in terms of consistency and validity checks. Large numbers of zero responses are common in WTP studies, and are found here; therefore, the Heckman selectivity model and log-transformed OLS are employed. The selectivity model is rejected, but test results indicate that the lognormal model yields efficient and unbiased estimates. The results give confidence in the WTP estimates obtained and, more generally, in CVM as a means of valuing publicly provided goods and in econometrics as a tool for analysing WTP results containing many zero responses.

Adolescent↗
PubMed2004

Mixed states on neural network with structural learning.

We investigated the properties of mixed states in a sparsely encoded associative memory model with a structural learning method. When mixed states are made of s memory patterns, s types of mixed states, which become equilibrium states of the model, can be generated. To investigate the properties of s types of the mixed states, we analyzed them using the statistical mechanical method. We found that the storage capacity of the memory pattern and the storage capacity of only a particular mixed state diverge at the sparse limit. We also found that the threshold value needed to recall the memory pattern is nearly equal to the threshold value needed to recall the particular mixed state. This means that the memory pattern and the particular mixed state can be made to easily coexist at the sparse limit. The properties of the model obtained by the analysis are also useful for constructing a transform-invariant recognition model.

Algorithms↗
PubMed2000

In situ adsorption studies at silica/solution interfaces by attenuated total internal reflection fourier transform infrared spectroscopy: examination of adsorption models in normal-phase liquid chromatography

ATR-FT-IR spectroscopy was employed to the study the adsorption of ethyl acetate and 2-propanol to the surface of thin silica sol-gel films in contact with n-heptane solutions. In situ vibrational spectra of silica-adsorbed species provided information regarding the mechanisms of solute retention and elution in normal-phase chromatography. Previous normal-phase chromatographic studies of ethyl acetate adsorption revealed nonlinear isotherms which were explained by both bilayer and adsorbate delocalization models. Infrared spectra of ethyl acetate at the silica surface versus concentration showed that nonlinear adsorption can be attributed to site heterogeneity, where adsorption to free silanols and surface-adsorbed water can be distinguished. Least-squares modeling of the data produced resolved spectra for the two sites and adsorption equilibrium constants that differed by about an order of magnitude. Adsorption of 2-propanol was best modeled by a single Langmuir isotherm showing no significant difference in adsorption energy for the two sites; 2-propanol was shown to easily displace ethyl acetate from the silica surface. Ethyl acetate could also displace 2-propanol from the silica, and least-squares modeling again revealed two-adsorbed-component spectra for ethyl acetate that were indistinguishable from spectra obtained when ethyl acetate adsorbed directly onto the surface.

Journal Article↗