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[Classical and non-classical taxonomy: where does the boundary pass?].

Rise of non-classical science during XX century had certain influence upon development of biological taxonomy. Scientific pluralism (especially normative naturalism of Laudan), contrary to positivist and early post-positivist treatments, made taxonomy acknowledged scientific discipline of its own right. The present state of some schools of taxonomy makes it possible to consider them as a part of non-classical science and constituting the non-classical taxonomy. The latter is characterized by the following most important features. Ontological substantiation of both classificatory approaches and particular classifications is requested which invalidates such formal approaches as nominalistic and phenetic (numerical) schools. This substantiation takes a form of content-wise background preferably causal models which include certain axioms and presumptions about taxonomic diversity being studied, together with its causes, and thus define initial conditions of classificatory procedures. From this viewoint, phylogenetic classificatory approach is the most developed part of non-classical taxonomy. The entire taxonomic diversity is structured into several aspects of different levels of generality, each being outlined by a particular consideration aspect. The latter makes personal knowledge constituting an irremovable part of any scientific statement about taxonomic diversity, thus opposition of "objectively" and "subjectively" elaborated classifications becomes vague. Interrelation of various species concepts corresponding to its different consideration aspects is described by uncertainty relation principle. Classificatory algorithms are to be compatible with the conditions of a background model to ensure particular classifications obtained by their means are interpretable within the same model: this is provided by the correspondence principle. Classification is considered as a taxonomic hypothesis, i.e. a conjectural judgement about structure of particular fragment of taxonomic diversity considered within given consideration aspect; wich is to be forwarded and tested according to certain rules. Recognition of different aspects of taxonomic diversity makes it "legal" to elaborate several classifications of equal status, each reflecting a particular aspect of a fixed fragment of that diversity. This viewpoint makes classical ideas of the "ultimate" Natural (whatever might be its definition) or the best reference systems futile. In general, any pretension of an approach to be "the best" in reflecting taxonomic divesrity is contr-productive. Instead, elaboration of particular spectra of complementary classifications becomes the main task of non-classical taxonomy which describes in sum the entire taxonomic diversity. So, not opposition but correct mutual interpretation of such classifications and uniting them into the comprehensive picture of taxonomic diversity become focal points of non-classical taxonomy.

Biodiversity↗

Improved interpretation of flow maps obtained by scanning laser Doppler flowmetry using a rat model of retinal artery occlusion.

PURPOSE: To improve the interpretation of Heidelberg Retina Flowmeter (HRF; Heidelberg Engineering GmBH, Dosselheim, Germany) flow maps by examining the influence of specific vascular structures and focus depth in the presence and absence of retinal blood flow. METHODS: HRF flow maps were recorded from the inferior retina of anesthetized Brown Norway rats over a wide range of focus levels, before and after laser occlusion of the retinal circulation. Analysis of the resultant flow maps showed that the sample window was positioned on a retinal artery, arteriole, or vein, or in a retinal capillary area, with or without a visible underlying choroidal vessel. The relationship between HRF-measured flow (arbitrary units) and focus depth was determined for each location. At the conclusion of each experiment, the effect of reduction of systemic blood pressure on the choroidal circulation and the level of background signal in the HRF flow map with no ocular blood flow were assessed. RESULTS: The strongest flow signals came from the retinal arteries, veins, and arterioles and were reduced to choroidal background level after occlusion of the central retinal artery. Larger choroidal vessels also contributed strong flow signals. In contrast, the flow signal from the retinal capillary area was weak and unaffected by retinal artery occlusion. Changing the depth of focus significantly altered the contribution from the major retinal arteries, arterioles, and veins, but no significant depth effect was seen for retinal capillaries or choroidal vessels. The HRF flow signal remaining when systemic blood pressure was reduced to zero was not significantly different from the capillary sampling location when the eye was normally perfused. CONCLUSIONS: In the pigmented rat eye, the HRF signal from retinal capillaries is not significantly different from the background noise unrelated to blood flow. Strong flow signals can be obtained from the retinal arteries, retinal arterioles, retinal veins, and choroidal vessels. Current HRF flow maps in the rat therefore reflect blood flow in the larger elements of the microvasculature rather than the capillary network.

Animals↗

Tempo and mode in hominid evolution.

The nature of human evolution has been viewed recently as a specific example of a more general model of evolution termed "punctuated equilibrium". The characteristics of this model are long periods of little or not evolutionary change (stasis) interspersed with periods of rapid (punctuated) morphological change. Careful analysis of the hominid fossil record over the past 4.0 million years, however, suggests no well documented examples of either stasis or punctuation. The evidence for the evolution of the hominid lineage is most reasonably interpreted by a model of more gradual change with periods of varying rates of evolution.

Anthropometry↗

Improving titrimetric techniques by modelling pH change in activated sludge systems.

Existing titrimetric techniques rely on a well defined hydrogen ion production rate. In particular, they are only suitable in circumstances in which constant background pH influencing reactions take place. This is rarely the case due to the presence of the carbonate acid/base system. In this paper, a model, which describes the influence of the nitrification process on pH and accounts for the action of the carbonate system, is presented. The validity of the model is tested by comparison of model predictions for the important state variables with that of experimental data from a batch oxidation of ammonium nitrogen. The two cases studied are the responses of an endogenously respiring nitrifying sludge to: an ammonium chloride pulse and a pulse of both bicarbonate and ammonium chloride. The results are most encouraging as the dynamic HPR response is mirrored by the model simulation. Furthermore, using the model for data interpretation, the initial nitrogen substrate levels are recovered. It is shown that this could not have been achieved in either case using existing titrimetric techniques.

Bioreactors↗

[An analysis of the functional heterogeneity of the sensory motor neuron synapse of the frog].

Four models of the amplitude fluctuations of postsynaptic potentials have been compared. Better agreement of convolution of the two binomial distributions and beta-model as compared to the binomial model is demonstrated. The beta-model is based on the assumption that the probability of the transmitter quantum release is a random variable which has beta distribution. The number of the quantum generators estimated by the beta-model is close to the number of synaptic boutons in the sensory-motor synapses of the frog. Investigation of this model has shown that the number of generators estimated by the binomial model may be interpreted as the number of transmitter release sites functioning with probabilities exceeding 0.2. Results obtained confirm the hypothesis concerning the functional heterogeneity of release sites at the frog interneuronal synapses.

Animals↗

Bayesian methods for quantitative trait loci mapping based on model selection: approximate analysis using the Bayesian information criterion.

We describe an approximate method for the analysis of quantitative trait loci (QTL) based on model selection from multiple regression models with trait values regressed on marker genotypes, using a modification of the easily calculated Bayesian information criterion to estimate the posterior probability of models with various subsets of markers as variables. The BIC-delta criterion, with the parameter delta increasing the penalty for additional variables in a model, is further modified to incorporate prior information, and missing values are handled by multiple imputation. Marginal probabilities for model sizes are calculated, and the posterior probability of nonzero model size is interpreted as the posterior probability of existence of a QTL linked to one or more markers. The method is demonstrated on analysis of associations between wood density and markers on two linkage groups in Pinus radiata. Selection bias, which is the bias that results from using the same data to both select the variables in a model and estimate the coefficients, is shown to be a problem for commonly used non-Bayesian methods for QTL mapping, which do not average over alternative possible models that are consistent with the data.

Alleles↗

Current and future approaches using genetically modified mice in endocrine research.

Genetically modified mouse models have been used widely to advance our knowledge in the field of endocrinology and metabolism. A number of different approaches to generate genetically modified mice are now available, which provide the power to analyze the role of individual proteins in vivo. However, there are a number of points to be considered in the use and interpretation of these models. This review discusses the advantages and disadvantages involved in the generation and use of different genetically modified mouse models in endocrine research, including conventional techniques (e.g., overexpression, knockout, and knock-in models), tissue- and/or time-specific deletion of target genes [e.g., Cre-loxP and short interfering (si)RNA transgenic approaches], and gene-trap approaches to undertake functional genomics. This review also highlights the many factors that should be considered when assessing the phenotype of these mouse models, many of which are relevant to all murine physiological studies. These approaches are a powerful means by which to dissect the function of genes and are revolutionizing our understanding of endocrine physiology and metabolism.

Animals↗

ADME evaluation in drug discovery. 5. Correlation of Caco-2 permeation with simple molecular properties.

The correlations between Caco-2 permeability (logPapp) and molecular properties have been investigated. A training set of 77 structurally diverse organic molecules was used to construct significant QSAR models for Caco-2 cell permeation. Cellular permeation was found to depend primarily upon experimental distribution coefficient (logD) at pH = 7.4, high charged polar surface area (HCPSA), and radius of gyration (rgyr). Among these three descriptors, logD may have the largest impact on diffusion through Caco-2 cell because logD shows obvious linear correlation with logPapp (r=0.703) when logD is smaller than 2.0. High polar surface area will be unfavorable to achieve good Caco-2 permeability because higher polar surface area will introduce stronger H-bonding interactions between Caco-2 cells and drugs. The comparison among HCPSA, PSA (polar surface area), and TPSA (topological polar surface area) implies that high-charged atoms may be more important to the interactions between Caco-2 cell and drugs. Besides logD and HCPSA, rgyr is also closely connected with Caco-2 permeabilities. The molecules with larger rgyr are more difficult to cross Caco-2 monolayers than those with smaller rgyr. The descriptors included in the prediction models permit the interpretation in structural terms of the passive permeability process, evidencing the main role of lipholiphicity, H-bonding, and bulk properties. Besides these three molecular descriptors, the influence of other molecular descriptors was also investigated. From the calculated results, it can be found that introducing descriptors concerned with molecular flexibility can improve the linear correlation. The resulting model with four descriptors bears good statistical significance, n = 77, r = 0.82, q = 0.79, s = 0.45, F = 35.7. The actual predictive abilities of the QSAR model were validated through an external validation test set of 23 diverse compounds. The predictions for the tested compounds are as the same accuracy as the compounds of the training set and significantly better than those predicted by using the model reported. The good predictive ability suggests that the proposed model may be a good tool for fast screening of logPapp for compound libraries or large sets of new chemical entities via combinatorial chemistry synthesis.

Caco-2 Cells↗

Why do shear bond tests pull out dentin?

It is widely accepted that a dentin shear bond test which pulls out dentin must mean that the adhesive strength is superior to the cohesive strength of the dentin. Using numerical modeling techniques, Van Noort et al. (1988, 1989) and DeHoff et al. (1995) alerted the scientific community that there were massive stress concentrations in the familiar dentin bond test. It is not inconceivable that these localized high tensile stresses could initiate cracks which diverge monolithically into dentin, leaving the interface unchallenged. To test this hypothesis, we developed a failure accumulation simulation program which determined localized failure interactively "on the fly" with a finite element solver, and also included brittle behavior, adhesive and cohesive failure, stochastic response, and dynamic remeshing. All of the familiar dentin bond variables were included in the simulation. A parallel experimental dentin bond test validation was run, and the fractography was examined in the scanning electron microscope for mode of failure. The simulation confirmed the tensile monolithic fracture hypothesis. It is also confirmed that dentin pull-out was partly due to the biomechanics of the test and did not necessarily mean superior adhesive strength or even that the cohesive strength of the dentin was reduced. There is clear need for a new technology for the evaluation of biological interfaces, and the present work has shown the vital role of numerical modeling in the interpretation of such experimental procedures.

Adhesiveness↗

Cytotoxicity of copper ions released from metal: variation with the exposure period and concentration gradients.

The aim of this work is to contribute to the elucidation of the cytotoxic process caused by the copper ions released from the biomaterials. Clonal cell lines UMR106 were used in the experiments. Copper ions were obtained from two different sources: copper salts and metal dissolution. Experiments carried out with constant ion concentrations (copper salts) were compared with those with concentrations that vary with time and location (dissolution of the metal). Present results and others previously reported could be interpreted through mathematical models that describe: (1) the variation of concentration of copper ions with time and location within a biofilm and (2) the variation of the killing rate with the concentration of the toxic ion and time. The large number of dead cells found near the copper sample with an average ion concentration below the toxic limit could be interpreted bearing in mind that these cells should be exposed to a local concentration higher than this limit. A logarithmic dependence between the number of cells and exposure time was found for nearly constant ion concentrations. Apparent discrepancies, observed when these results and those of different researchers were contrasted, could be explained considering the dissimilar experimental conditions such as the source of the ions and their local concentration at real time.

Animals↗

Intelligent semantic interoperability: Integrating knowledge, terminology and information models to support stroke care.

INTRODUCTION: Electronic patient record (EPR) systems for the continuity of care for stroke patient are under development. These systems are based on standards such as for clinical practice, vocabularies, and the HL7 information model. PROBLEM STATEMENT: In order to achieve intelligent semantic interoperability, knowledge about evidence based patient care, vocabulary and information models need to be integrated. METHODOLOGY: A format was developed in which the clinical knowledge, clinical terminology, and standard information models are integrated as specification for the technical implementation of electronic health systems and electronic messages. This format is verified by clinicians and technicians. RESULTS: The document structure consists of meta-information such as version control and changes, purpose of the clinical content, evidence from the literature, variables and values, terminology used, guidelines for application and interpretation, HL7 message models, coding, and technical data specification. Further, XML message excerpts, archetypes and screen designs are developed from these documents to facilitate implementation. CONCLUSION: The combination of these aspects in one document creates valuable content for intelligent semantic interoperability by means of development of messages and systems.

Continuity of Patient Care↗

A computer model to analyze the cost-effectiveness of hormone replacement therapy.

This paper gives a detailed presentation of a computer model for evaluating the cost-effectiveness (CE) of hormone replacement therapy (HRT), describing the model's design, structure, and data requirements. The model needs data specified for costs, quality of life, risks, and mortality rates. As an illustration, the CE of HRT in Sweden is calculated. Two treatment strategies are evaluated for asymptomatic women: estrogen-only therapy and estrogen combined with a progestin. The model produces similar results compared with earlier studies. The CE ratios improve with the size of the risk reduction and generally with age. Further, estrogen-only therapy is associated with a lower cost per gained effectiveness unit compared with combined therapy. Uncertainty surrounding the long-term effects of HRT means that the CE estimates should be interpreted carefully. The model permits the inclusion of indirect costs and costs in added life-years, allowing the analysis to be made from a societal perspective, which is an improvement relative to previous studies.

Aged↗

[Regulatory reversible enzymic reactions. Theoretical analysis].

A mathematical model has been derived and analysed describing the relationship between the rate of an enzymic reaction S1 E(R,T)A in equilibrium S2 and concentrations of substrates S1 and S2 and their analogue A capable of reversible binding to active sites of an olygomeric enzyme E(R, T). The conditions have been presented for the model to describe various types of kinetic curves, sygmoidal, curves with extremuma and intermediate plateau. The regions of parameter values have been estimated within which isosteric product activation can be observed in reactions S1 in equilibrium E(R,T) S2 and S1 E(R,T) in equilibrium S2. Two phenomena registered in experiments with olygomeric enzymes have been interpreted in the model terms, namely, the undirectional influence of isosteric and allosteric effectors on the rates of forward and reverse reactions and occurence of a reversible enzymic reaction in thermodynamically unfavourable direction. The results presented are shown to be valid for multisubstrate reactions catalysed by olygomeric enzyme E(R, T).

Enzymes↗

Direct detection of domains in phospholipid bilayers by grazing incidence diffraction of neutrons and atomic force microscopy.

The geometry of domains in phospholipid bilayers of binary (1:1) mixtures of synthetic lecithins with a difference in chain length of four methylene groups has been studied by two independent, direct and complementary methods. Grazing incidence diffraction of neutrons provided gel domain sizes of less than 10 nm in both the gel and the coexistence phase of the mixture, while no domains were detected for the fluid phase. For the coexistence region, the neutron data suggest that domains grow in number rather than in size with decreasing temperature. Atomic force microscopy was used to study gel phase size and shape of the domains. The domains imaged by atomic force microscopy exhibit a rather irregular shape with an average size of 10 nm, thus confirming the neutron results for this phase. The good agreement between atomic force microscopy and neutron results, despite the completely different nature of their observables, has potential for the future development of refined models for the interpretation of neutron data from heterogeneous membranes in terms of regularly spaced and spatially extended scatterers.

Calorimetry, Differential Scanning↗

Popular opinion leaders and HIV prevention peer education: resolving discrepant findings, and implications for the development of effective community programmes.

A series of community-level trials undertaken in the United States over the past 10 years established the effectiveness of an HIV prevention intervention that systematically identifies, recruits, trains, and engages the popular opinion leaders (POLs) of a population to serve as behaviour change endorsers. Recently, several investigators reported unsuccessful attempts to implement peer education programmes for men who have sex with men in the United Kingdom and raised questions about whether peer-based programmes are effective or feasible. However, POL is a theory-based and very specialized intervention, and the UK peer education programmes did not incorporate many of POL's core or essential elements. Consequently, they were not evaluations of POL. In this article, core elements of the popular opinion leader model are presented; interpretations are made of possible reasons for the discrepant findings of the UK peer education and US POL interventions; and practical issues for applied programme development are discussed.

HIV Infections↗

When the smile is a cue to familiarity.

The question discussed in the two following experiments concerns the effect of facial expressions on face recognition. Famous and unknown faces with neutral or smiling expression were presented for different inspection durations (15 ms vs 1000 ms). Subjects had to categorize these faces as famous or unknown (Experiment 1), or estimate their degree of familiarity on a rating scale (Experiment 2). Results showed that the smile increased ratings of familiarity for unfamiliar faces (Experiments 1 and 2) and for famous faces (Experiment 2). These data are discussed in the framework of current face-recognition models and are interpreted in terms of social value of the smile. It is proposed that the smiling bias found here acts at the level of the decision process.

Cues↗

Age-specific patterns of genetic variance in Drosophila melanogaster. I. Mortality.

PETER MEDAWAR proposed that senescence arises from an age-related decline in the force of selection, which allows late-acting deleterious mutations to accumulate. Subsequent workers have suggested that mutation accumulation could produce an age-related increase in additive genetic variance (VA) for fitness traits, as recently found in Drosophila melanogaster. Here we report results from a genetic analysis of mortality in 65,134 D. melanogaster. Additive genetic variance for female mortality rates increases from 0.007 in the first week of life to 0.325 by the third week, and then declines to 0.002 by the seventh week. Males show a similar pattern, though total variance is lower than in females. In contrast to a predicted divergence in mortality curves, mortality curves of different genotypes are roughly parallel. Using a three-parameter model, we find significant VA for the slope and constant term of the curve describing age-specific mortality rates, and also for the rate at which mortality decelerates late in life. These results fail to support a prediction derived from MEDAWAR's "mutation accumulation" theory for the evolution of senescence. However, our results could be consistent with alternative interpretations of evolutionary models of aging.

Aging↗

Theory of planned behavior-based models for breastfeeding duration among Hong Kong mothers.

BACKGROUND: The theory of planned behavior (TPB) has been used to explain breastfeeding behaviors in Western cultures. Theoretically-based investigations in other groups are sparse. OBJECTIVE: To evaluate cross-cultural application of TPB-based models for breastfeeding duration among new mothers in Hong Kong. METHOD: First-time breastfeeding mothers (N = 209) with healthy newborns provided self-reports of TPB predictor variables during postpartum hospitalization and information about breastfeeding experiences at 1, 3, 6, 9, and 12 months postdelivery or until they weaned. Three predictive models were proposed: (a) a strict interpretation of the TPB with two added proximal predictors of breastfeeding duration; (b) a replication with modification of the TPB-based model for more fully employed breastfeeding mothers from a previous study (Duckett et al., 1998); and (c) a model that posited perceived control (PC) as a mediating factor linking TPB motivational variables for breastfeeding with breastfeeding intentions and behavior. LISREL was used for the structural equation modeling analyses. RESULTS: Explained variance in PC and duration was high in all models. Overall fit of the strict TPB model was poor (GOFI = 0.85). The TPB for breastfeeding employed women and the PC-mediated models fit equally well (GOFI = 0.94; 0.95) and residuals were small (RMSR = 0.07). All hypothesized paths in the PC-mediated model were significant (p <.05); explained variance was 0.40 for perceived control and 0.36 for breastfeeding duration. DISCUSSION: Models were interpreted in light of the TPB, previous findings, the social context for breastfeeding in Hong Kong, and statistical model-building. Cross-cultural measurement issues and the need for prospective designs are continuing challenges in breastfeeding research.

Adult↗