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At least 1,081 records · Page 60Linked to original sources
PubMed2006

Structural model analysis of multiple quantitative traits.

We introduce a method for the analysis of multilocus, multitrait genetic data that provides an intuitive and precise characterization of genetic architecture. We show that it is possible to infer the magnitude and direction of causal relationships among multiple correlated phenotypes and illustrate the technique using body composition and bone density data from mouse intercross populations. Using these techniques we are able to distinguish genetic loci that affect adiposity from those that affect overall body size and thus reveal a shortcoming of standardized measures such as body mass index that are widely used in obesity research. The identification of causal networks sheds light on the nature of genetic heterogeneity and pleiotropy in complex genetic systems.

Adipose Tissue↗
PubMed2003

The parameter-free track structure model of Scholz and Kraft for heavy-ion cross sections.

The "parameter-free", "local effects" theory of Scholz and Kraft is an extension to mammalian cells of the theory of RBE for dry enzymes and viruses of Butts and Katz. Its claim for parameter freedom has been challenged elsewhere. Here we examine its conceptual base and find errors in its use of the physical concept of cross section and its neglect of the radiobiological relationship between target size and radiosensitivity in evaluating the radiation damage to "point targets".

Animals↗
PubMed2005

Multiple-breed genetic inference using heavy-tailed structural models for heterogeneous residual variances.

Multiple-breed genetic models recently have been demonstrated to account for the heterogenous genetic variances that exist between different beef cattle breed groups. We extend these models to allow for residual heteroskedasticity (heterogeneous residual variances), specified as a function of fixed effects (e.g., sex, breed proportion, breed group heterozygosity) and random effects such as contemporary groups (CG). We additionally specify the residual distributions to be either Gaussian or based on heavier-tailed alternatives such as the Student's t or Slash densities. For each of these three residual densities using either homoskedastic (homogeneous variance) or heteroskedastic error specifications, we analyzed 22,717 postweaning gain records from a Nelore-Hereford population based on a Markov chain Monte Carlo animal model implementation. The heteroskedastic Student's t error model (with estimated df = 7.33 +/- 0.48) was clearly the best-fitting model based on a pseudo-Bayes factor criterion. Breed group heterozygosity and, to a lesser extent, calf sex seemed to be marginally important sources of residual heteroskedasticity. Specifically, the residual variance in F1 animals was estimated to be 0.70 +/- 0.16 times that for purebreds, whereas the male residual variance was estimated to be 1.13 +/- 0.09 times that for females. The CG effects were important random sources of residual heteroskedasticity (i.e., the coefficient of variation of CG-specific residual variances was estimated to be 0.72 +/- 0.06). Purebred Nelores were estimated to have a larger genetic variance (124.84 +/- 21.75 kg2) compared with Herefords (40.89 +/- 6.70 kg2) under the heteroskedastic Student's t error model; however, the converse was observed from results based on a homoskedastic Student's t error model (46.24 +/- 10.90 kg2 and 60.11 +/- 8.54 kg2, respectively). These results indicate that allowing for robustness to outliers and accounting for heteroskedasticity of residual variances has potentially important implications for variance component and genetic parameter estimates from data on multiple-breed populations.

Animals↗
PubMed1982

On fundamental and phenomenological models, structure and mechanical properties of collagen, elastin and glycosaminoglycan complexes.

This paper reviews the structure (from molecular to macroscopic level) of collagen, elastin and glycosaminoglycans, with special reference to their functional properties and to how their behavior can be elucidated from in vitro manipulations of the tissues by biochemical means. Modes to analyse the mechanical behavior are briefly discussed and exemplified by data from reconstituted collagenous "tissue". It is concluded that the basic equation for the "non-linear elasticity" component in Fung's law (and for the reconstituted "tissue" a modification of it) is a powerful tool for analysis of the physiological range of the stress-strain curve. Further, enzymatic "dissection" of one tissue element at a time provides a valuable method for the analysis of tissue element interactions. This approach is illustrated with data from aortic tissue. It is shown that the mechanical properties of the aorta depend on the interaction between elasticity and collagenous elements and that the strength of the tissue is not derived from its collagen fibers per se.

Animals↗
PubMedDate not supplied

Determination of material constants and hydraulic strengthening of trabecular bone through an orthotropic structural model.

A statistical mathematical model is used to describe the viscoelastic behavior of trabecular bone from the description of its microstructure. Trabecular bone is regarded as an orthotropic composite material consisting of two phases: The trabeculae, modelled as a non-linear elastic material, and the marrow, modelled as a Maxwell element. The macroscopic constitutive equation contains, as parameters, the constants of the material phases' constitutive equations, the respective volume fractions and parameters descriptive of the geometry of trabecular bone. With this model, the contribution of the marrow to the mechanical behavior of trabecular bone is determined and it is calculated that, under a step load and at strain rate, 10 min-1, the marrow can bear about 25% of the applied load. The constants of the material phases are also calculated from a series of stress-relaxation curves on trabecular bone specimens. It is concluded that the trabeculae display non-linear elastic behavior.

Aged↗
PubMed1976

[Structural model of factor VIII complex].

Gel filtration patterns on Sepharose CL-2B of functional subunits (procoagulant, ristocetin cofactor, antigen) derived from highly purified human factor VIII indicate that the native, intact complex is reproducibly eluted in the void volume. The complex is, however, degraded by proteolytic (and possibly other) enzymes contaminating the purified material during dialysis at room temperature. Resulting degradation products were fractionated by gel filtration and characterized by SDS-polyacrylamide electrophoresis. Our results suggest that factor VIII consists of identical subunits (mol. wt. about 500 000) which might be linked together by hydrophobic bonds. Only native high molecular weight aggregates posses ristocetin cofactor activity.

Factor VIII↗
PubMed1999

Drinking and flying: a structural model.

BACKGROUND: Under a recent revision of the European Joint Aviation Authorities operations regulations it has been prohibited to act as a crew member of an aircraft with a BAC of greater than 0.02%. METHODS: This survey of UK Civil Aviation Authority pilots suggests that over 50% of respondents may have flown an aircraft with a BAC of greater than this prescribed amount. RESULTS: Professional pilots were found to be heavier drinkers than private pilots and were also more likely to infringe the 0.02% BAC rule. CONCLUSION: Analysis of the data using path analysis suggests that professional pilots may be more prone to offending as a result of training in a "drinking culture" and as a response to commercial pressures in the industry.

Adult↗
PubMed1999

Structure, modelling, and molecular dynamics studies of the inhibition of protein tyrosine phosphatase 1B by sulfotyrosine peptides.

The protein tyrosine phosphatases comprise a class of enzymes that are crucial for the regulation of a number of cellular processes. Because of this, they are attracting increasing attention, not only as legitimate therapeutic targets, but also because of their relationship to many fundamental cellular processes. Certain sulfotyrosine peptides derived from casein are known to be good inhibitors of the protein tyrosine phosphatase, PTP1B. In this study, NMR transfer nuclear Overhauser effect studies have been used to ascertain the bound-state conformation adopted by the 12-amino acid residue casein-derived peptide, CAS200 (NANEEE(sY)SIGSA) and N-terminal truncated forms of this peptide, CAS203 and CAS205. Each of the peptides were found to bind in an extended beta-strand conformation. Extensive molecular modelling and molecular dynamics simulations of the PTP1B/peptide complexes, in a fully hydrated model, allowed a detailed description of the potential sources of the binding interactions to be developed. In agreement with the NMR studies, the modelling provided a picture of binding of CAS200 in which only the central (E203-I208) residues contributed significantly to the binding while the 3 N-terminal and 3 C-terminal residues were quite fluxional. Critical cationic surface residues, lying near to, but outside the active site pocket were the source of strong stabilizing forces that complemented the stabilizing interactions of the active site pocket. Electrostatic, hydrophobic, and hydrogen bonding interactions, in a residue specific manner, were all found to make significant contributions to the binding of these inhibitors.

Binding Sites↗