An approximate multitrait model for genetic evaluation in dairy cattle with a robust estimation of genetic trends (Open Access publication)

In a stochastic simulation study of a dairy cattle population three multitrait models for estimation of genetic parameters and prediction of breeding values were compared. The first model was an approximate multitrait model using a two-step procedure. The first step was a single trait model for all traits. The solutions for fixed effects from these analyses were subtracted from the phenotypes. A multitrait model only containing an overall mean, an additive genetic and a residual term was applied on these preadjusted data. The second model was similar to the first model, but the multitrait model also contained a year effect. The third model was a full multitrait model. Genetic trends for total merit and for the individual traits in the breeding goal were compared for the three scenarios to rank the models. The full multitrait model gave the highest genetic response, but was not significantly better than the approximate multitrait model including a year effect. The inclusion of a year effect into the second step of the approximate multitrait model significantly improved the genetic trend for total merit. In this study, estimation of genetic parameters for breeding value estimation using models corresponding to the ones used for prediction of breeding values increased the accuracy on the breeding values and thereby the genetic progress.     

Risk Communications: Around the World Neural Network Models for Assessing Road Suitability for Dangerous Goods Transport

This article describes a methodology for assessing the degree of remedial action required to make short stretches of a roadway suitable for dangerous goods transport (DGT). The methodology is based on the evaluation of a set of variables that have a bearing on DGT risk. The large number of variables involved made it necessary to apply a supervised approach based on expert criteria. The result was a knowledge base that can be used both to estimate DGT risk for new stretches of roadway and to determine sources of risk without having to rely on an expert. A number of multivariate statistical analysis techniques were tested for the construction of the model, namely linear discriminant analysis with a prior reduction in dimensionality, multilayer perceptrons, and support vector machines. The results obtained from a test sample show that the support vector machines represented expert knowledge most reliably. A graphic representation of the risk index for a studied stretch of roadway results in a map of the level of DGT risk for that roadway.     

Visual representation of DNA sequences for exon detection using non-parametric spectral estimation techniques

This paper presents a new approach for modeling of DNA sequences for the purpose of exon detection. The proposed model adopts the sum-of-sinusoids concept for the representation of DNA sequences. The objective of the modeling process is to represent the DNA sequence with few coefficients. The modeling process can be performed on the DNA signal as a whole or on a segment-by-segment basis. The created models can be used instead of the original sequences in a further spectral estimation process for exon detection. The accuracy of modeling is evaluated evaluated by using the Root Mean Square Error (RMSE) and the R-square metrics. In addition, non-parametric spectral estimation methods are used for estimating the spectral of both original and modeled DNA sequences. The results of exon detection based on original and modeled DNA sequences coincide to a great extent, which ensures the success of the proposed sum-of-sinusoids method for modeling of DNA sequences.     

The extremely low frequency electrical properties of plant stems

The electrical properties (variation of capacitance and conductance with frequency) of a plant stem can be conveniently measured in vivo by time domain dielectric spectroscopy. In this technique a voltage step is applied to a stem. The resulting polarization current is sampled by a microprocessor and Fourier-transformed to yield these properties. Spectra were obtained for seven electrode separations along a Poinsettia stem. The inverse capacitance and conductance were plotted vs separation for 50 frequencies from .35 to 350 Hz. Least-square fits yielded the effective dielectric constant and conductivity of the stem over this frequency range. In this way electrode effects were eliminated. A similar procedure was carried out for Coleus. A log-log plot of dielectric constant vs frequency shows a two-stage linear decrease for both plants. The conductivity is primarily DC. The dielectric loss decreases smoothly with frequency for Coleus. These results are compared to those for bone and the inorganic material hollandite. The dielectric properties seem best described by a cooperative, many-body approach.     

A Likelihood Ratio Test for the Nonparametric Behrens‐Fisher Problem

The nonparametric Behrens‐Fisher hypothesis is the most appropriate null hypothesis for the two‐sample comparison when one does not wish to make restrictive assumptions about possible distributions. In this paper, a numerical approach is described by which the likelihood ratio test can be calculated for the nonparametric Behrens‐Fisher problem. The approach taken here effectively reduces the number of parameters in the score equations to one by using a recursive formula for the remaining parameters. The resulting single dimensional problem can be solved numerically. The power of the likelihood ratio test is compared by simulation to that of a generalized Wilcoxon test of Brunner and Munzel. The tests have similar power for all alternatives considered when a simulated null distribution is used to generate cutoff values for the tests. The methods are illustrated on data on shoulder pain from a clinical trial.     

Phytotoxic conjugates of indole-3-acetic acid: potential agents for biochemical selection of mutants in conjugate hydrolysis

Two strategies for selection of plant mutants altered in their ability to hydrolyze IAA conjugates are described. The rationale for both strategies is to form a conjugate between two chemical moieties in which one moiety is a toxin. The first strategy makes use of a toxic auxin analogue. For this approach a series of halogenated IAA analogues were tested for toxic properties to Lemna gibba and Zea mays. Several halogenated analogues were toxic, but only 5-Br-IAA was highly toxic to both species. The second strategy required a toxic compound with suitable functional groups to allow IAA conjugation. The mycotoxin patulin was found to be a suitable candidate. Uptake and hydrolysis of IAA-conjugates was studied in order to better define the conditions required for conjugate analogues to be effectively employed for selections.     

Calculation of viscometric constants, hydrodynamic volume, polymer-solvent interaction parameter, and expansion factor for three polysaccharides with different chain conformations

The viscometric constants, K and a, for three polysaccharides: hydroxyethylcellulose (HEC); hydroxypropylcellulose (HPC); and chitosan, were calculated at 30 degrees C using intrinsic viscosity, [eta] and molecular weight (M(n), M(w), M(z)) data. The polydispersity correction factor, q(MHS), and hydrodynamic volume for each polymer sample were also calculated. The value of q(MHS) for the polymer samples was taken into account in the calculation of the viscometric constants. The polymer-solvent interaction parameters for the three polysaccharides were estimated by both semiempirical and numerical methods using intrinsic viscosity and molecular weight data. Hydrodynamic expansion factors were also estimated using the latter data. The quality of the solvents for the three polymers was compared using exponent a, polymer-solvent interaction parameter, and expansion factor data. This study resulted in the following constants for: The values of 0.60, 1.08, and 0.885 for exponents a indicate that HEC, HPC, and chitosan behave as a flexible random coil, linear and extended conformations, respectively. The values of exponents a for the three polysaccharides appear to be inversely related to their K values. The results of the expansion factor were consistent with the results of exponent a and polymer-solvent interaction parameters.     

A monochromosomal hybrid cell assay for evaluating the genotoxicity of environmental chemicals

The development and utilization of a monochromosomal hybrid cell assay for detecting aneuploidy and chromosomal aberrations are described. The monochromosomal hybrid cell lines were produced by a two-step process involving transfer of a marker bacterial gene to a human chromosome and then by integration of that human chromosome into a mouse complement of chromosomes through microcell fusion. For chemically induced aneuploidy, the segregation of a single human chromosome among mouse chromosomes is used as a cytogenetic marker. The genetic assay for aneuploidy is based on the ability of the cells to grow in a medium that selects for the loss of the human chromosome. The assay for clastogenicity is based on survival of the cells after treatment with the chemicals in medium that selects for retention of the human chromosome but loss of its segment containing diphtheria toxin locus. The assays greatly simplify the detection of chromosomal aberrations induced by environmental factors at low-dose levels.     

Demand for human allograft tissue in Canada

There is relatively little known about the demand for allograft tissues in Canada. The Canadian Council for Donation and Transplantation (CCDT) is a national advisory body that undertook a comprehensive “market survey” to estimate surgical demand for human allograft tissues in Canada. The report “Demand for Human Allograft Tissue in Canada” reflects survey results sent to 5 prominent User Groups. User Groups were identified as orthopaedic surgeons; neurosurgeons; corneal transplant surgeons; plastic surgeons, specifically those at Canadian Burn Units; and cardiac surgeons (adult and paediatric surgery). The demand for allograft grafts was determined and then extrapolated across the total User Group and then increases in allograft tissue use over the next 1–2 years across User Groups were predicted. The overall response rate for the survey was 21.4%. It varied from a low of 19.6% for the orthopaedic survey to a high of 40.5% for the corneal survey. The estimated current demand for allograft tissue in Canada ranges from a low of 34,442 grafts per year to a high of 62,098 grafts per year. The predicted increase in use of allograft tissue over the next 1–2 year period would suggest that annual demand could rise to somewhere in the range of 42,589–72,210 grafts. The highest rated preferences (98% and 94%) were for accredited and Canadian tissue banks, respectively. This study represents a key step in addressing the paucity of information concerning the demand for allograft tissue in Canada.     

隐马尔科夫过程在生物信息学中的应用

隐马尔科夫过程（hidden markov model,简称HMM）是20世纪70年代提出来的一种统计方法,以前主要用于语音识别。1989年Churchill将其引入计算生物学。目前,HMM是生物信息学中应用比较广泛的一种统计方法,主要用于：线性序列分析、模型分析、基因发现等方面。对HMM进行了简明扼要的描述,并对其在上述几个方面的应用作一概略介绍。     

Estimates of time and propensity for dental treatment among institutionalised elders

The oral health and concerns of elderly residents were surveyed in a stratified random selection of 41 long-term care facilities in Vancouver. The residents who could participate were examined and interviewed to determine their oral health and concerns about dental treatment. The need and time required for treatment were estimated in six groups to reflect the propensity for treatment in dentate and edentate subjects. The propensity for treatment was high in about one-third of the participants whereas it was unlikely that one-tenth of those examined would ever use a dental service. In general, there was a widespread need for a diagnostic service because so few had been examined by a dentist in the previous year. Prosthodontics accounted for most of the treatment in all of the propensity groups, with substantially more time required by the dentate residents. There was also a substantial need for management of mucosal pathoses and oral hygiene and, to a lesser extent, for dental restorations and endodontics. Overall, our estimates indicate a substantial need for dental treatment among residents of long-term care facilities, although the need is reduced by half if the propensity for treatment is considered.     

Development of a mathematical model for evaluating the dynamics of normal and apoptotic Chinese hamster ovary cells

A metabolic flux based methodology was developed for modeling the metabolism of a Chinese hamster ovary cell line. The elimination of insignificant fluxes resulted in a simplified metabolic network which was the basis for modeling the significant metabolites. Employing kinetic rate expressions for growing and non-growing subpopulations, a logistic model was developed for cell growth and dynamic models were formulated to describe culture composition and monoclonal antibody (MAb) secretion. The model was validated for a range of nutrient concentrations. Good agreement was obtained between model predictions and experimental data. The ultimate goal of this study is to establish a comprehensive dynamic model which may be used for model-based optimization of the cell culture for MAb production in both batch and fed-batch systems.     

Consistent Sets of Spectrophotometric Chlorophyll Equations for Acetone, Methanol and Ethanol Solvents

A set of equations for determining chlorophyll a (Chl a) and accessory chlorophylls b, c ₂ , c ₁ + c ₂ and the special case of Acaryochloris marina, which uses Chl d as its primary photosynthetic pigment and also has Chl a, have been developed for 90% acetone, methanol and ethanol solvents. These equations for different solvents give chlorophyll assays that are consistent with each other. No algorithms for Chl c compounds (c ₂ , c ₁ + c ₂) in the presence of Chl a have previously been published for methanol or ethanol. The limits of detection (and inherent error, ± 95% confidence limit), for chlorophylls in all organisms tested, was generally less than 0.1 μg/ml. The Chl a and b algorithms for green algae and land plants have very small inherent errors (< 0.01 μg/ml). Chl a and d algorithms for Acaryochloris marina are consistent with each other, giving estimates of Chl d/a ratios which are consistent with previously published estimates using HPLC and a rarely used algorithm originally published for diethyl ether in 1955. The statistical error structure of chlorophyll algorithms is discussed. The relative error of measurements of chlorophylls increases hyperbolically in diluted chlorophyll extracts because the inherent errors of the chlorophyll algorithms are constants independent of the magnitude of absorbance readings. For safety reasons, efficient extraction of chlorophylls and the convenience of being able to use polystyrene cuvettes, the algorithms for ethanol are recommended for routine assays of chlorophylls. The methanol algorithms would be convenient for assays associated with HPLC work.     

Automatic containment sampling of recombinant escherichia coli fermentations

A containment sampling system for shake flasks and fermentors has been developed from a blood collection system used in hospitals. The core of the system is a collection vial with a vacuum inside. When a needle connected to the fermentation fluid penetrates a rubber seal on the vial, a sample is withdrawn. The system has been developed in two versions, a manual method for shake flasks, and an automated version for fermentors including cool storage of samples. The sampling system offers the same safety for fermentation containment as the original system offers safety for patients and hospital staff. (c) 1992 John Wiley & Sons, Inc.     

Orientational relaxation time of bottom-heavy squirmers in a semi-dilute suspension

One of the important quantities to characterize unsteady behaviour of a cell suspension is the orientational relaxation time, which is the time scale for a micro-organism to re-orientate to its preferred direction from disorientated conditions. In this paper, a swimming micro-organism is modelled as a squirming sphere with prescribed tangential surface velocity, in which the centre of mass of the sphere is displaced from the geometric centre (bottom-heaviness). The orientational relaxation time of bottom-heavy squirmers in a suspension is investigated both analytically and numerically. The three-dimensional movement of 64 identical squirmers in a fluid otherwise at rest, contained in a cube with periodic boundary conditions, is dynamically computed, for random initial positions and orientations. The effects of volume fraction of squirmers, the bottom-heaviness and the squirming mode on the relaxation time are discussed. The results for a semi-dilute suspension show that both the mean stresslet strength and the orientational relaxation time decrease from those for a dilute suspension. We also observe a stress overshoot in some cases. The mechanism for this is different from that for a visco-elastic fluid, and is explained by the change with time of the orientation of squirmers.     

A new pairwise folding potential based on improved decoy generation and side-chain packing

A new force field for pairwise residue interactions as a function of C(alpha) to C(alpha) distances is presented. The force field was developed through the solution of a linear programming formulation with large sets of constraints. The constraints are based on the construction of >80,000 low-energy decoys for a set of proteins and requiring the decoy energies for each protein system to be higher than the native conformation of that particular protein. The generation of a robust force field was facilitated by the use of a novel decoy generation process, which involved the rational selection of proteins to add to the training set and included a significant energy minimization of the decoys. The force field was tested on a large set of decoys for various proteins not included in the training set and shown to perform well compared with a leading force field in identifying the native conformation for these proteins.     

Cementum annulation and age determination in Homo sapiens. II. Estimates and accuracy

The cementum annulation aging technique was evaluated in a sample of 80 clinically extracted premolars (age range 11–70 years). Demineralized thin sections (7μm) stained with hematoxylin were used. The correlation (r) between age and adjusted count (number of annulations added to age of tooth eruption) was 0.78 for the entire sample (N = 73) and 0.86 for a subsample in which teeth with periodontal disease were excluded (N = 55). Standard error of the estimates ranged from 4.7 to 9.7 years depending on sex and health status of the tooth. The technique provided significantly better estimates for females than for males. The overall inaccuracy (mean absolute error) of the technique was 6.0 years, with a bias (mean error) of 0.26 years. Reduced major axis regression of adjusted count on age produced a slope of 0.797 for the entire sample and 0.889 for the nonperiodontal disease subsample. These slopes are consistent with a hypothesis of annual deposition of cementum rings given a decrease in cementogenesis with increasing age.     

Following the course of human leptospirosis: evidence of a critical threshold for the vital prognosis using a quantitative PCR assay

In order to follow the course of acute human leptospirosis, an ELISA microtiter plate hybridization method was developed for the quantitative determination of Leptospira spp. in biological samples after PCR. The biotin-labelled amplified product (331 bp from the rrs gene) was hybridized with a complementary capture probe covalently linked onto aminated polystyrene wells, and detected using a colorimetric reaction. The mean detection limit was 50 copies per 10 microl. In a prospective study of human leptospirosis cases, we obtained evidence that a density of 10(4) leptospires per ml of blood is a critical threshold for the vital prognosis of the patients. The practicability of the method makes it suitable for use in tropical areas for multicentric studies. Such studies could lead to a better knowledge of the natural history of the human disease. The method is also suitable for experimental evaluation of improved antibiotic treatments for leptospirosis.