Characterization of the equine glycoprotein hormone alpha-subunit gene reveals divergence in the mechanism of pituitary and placental expression

The equine glycoprotein hormone alpha-subunit gene is expressed in both pituitary and placenta, unlike that of all other nonprimate mammals studied, in which expression is limited to pituitary. Previous studies of the 5'-flanking region of the equine alpha-subunit promoter have revealed unique characteristics as well as similarities with the human alpha-subunit promoter, which demonstrates a similar pattern of tissue-specific expression. We have cloned and sequenced the equine alpha-subunit gene and have used tissue culture systems and transgenic mice to characterize its expression. Unlike the human promoter, the cloned equine alpha-subunit promoter failed to direct trophoblast-specific expression in either tissue culture or transgenic mouse models, suggesting an entirely different mechanism for expression. In contrast, the equine alpha-subunit promoter was able to direct gonadotroph expression in both tissue culture and transgenic mouse models. In alphaT3-1 cells, 550 base pair (bp) was sufficient for expression. This expression involves promoter elements identified in other species as playing a role in gonadotroph expression, but mutation of these elements reveals differences in their relative contributions to promoter activity. In mice, 2800 bp of 5'-flanking sequence allowed specific expression in gonadotrophs but not in thyrotrophs or placenta. The pattern of estrogen regulation observed in transgenic mice matched neither the repression that has been observed with human and bovine alpha-subunit promoters in transgenic mice nor the stimulation in mRNA levels reported in mares, suggesting a unique mechanism that is not recapitulated in the transgenic model. Thus the equine alpha-subunit promoter uses a combination of conserved and unique features of gene regulation to direct its pattern of tissue-specific expression.     

The application of Weibull statistics to the strength of railway ballast

The tensile strengths of six types of ballast for various size fractions were investigated and quantified using Weibull statistics. For a given ballast and a given size fraction, the strengths follow the Weibull distribution reasonably well. However, it was found the size effect on strength implied by Weibull statistics for bulk failure of particles, is not consistent with measured values. Various possible reasons for this are explored, namely that the grinding process at the quarry may offer a proof test for ballast, that some ballasts may not be homogeneous or isotropic, and finally that surface fracture rather than bulk fracture may dominate.The authors would like to thank Lafarge Aggregates Ltd and Groundwork Hertfordshire for their financial and technical support for this project, which was funded though the Landfill Tax Credit Scheme.     

Announcements

 This paper examines the yielding of brittle granular materials subjected to one-dimensional compression. For an aggregate of uniform grains, at low stresses there is negligible reduction in voids ratio, and at high stresses voids ratio reduces approximately logarithmically with stress as a distribution of particle sizes evolves. A suitable definition of yield would appear to be the point of maximum curvature on a plot of voids ratio against the logarithm of stress, corresponding to the onset of grain fracture. It is proposed that the yield stress is approximately proportional to the average or Weibull 37% tensile strength of the particles in the aggregate. One-dimensional compression tests were performed on aggregates of brittle breakfast cereals, (cornflakes, rice krispies) and pasta and compared with the results for a typical one-dimensional compression test on dense silica sand at much higher stress levels. In addition, the tensile strengths of 30 particles for each material were determined by compression between flat platens, and found to satisfy the Weibull distribution. It is found that if voids ratio is plotted against the logarithm of stress, then yield occurs at much lower stresses for the cereals and pasta than for the dense silica sand, typically by two orders of magnitude. However, if voids ratio is plotted against the logarithm of stress normalised by the Weibull 37% tensile strength of the constituent grains, then the yielding region for each material is approximately the same. This confirms the proposed definition of yield as suitable, and that the yield stress determined in this way is approximately proportional to the tensile strength of the grains. The constant of proportionality is in the range 0.1–0.3, and this is consistent with observed heterogeneous stress distributions in discrete element simulations. Received: 12 June 2001     

A MICROCRACK GROWTH LAW FOR MULTIAXIAL FATIGUE

Within the past decade, critical plane approaches have gained increasing support based on correlation of experimentally observed fatigue lives and microcrack orientations under predominately low cycle fatigue (LCF) conditions for various stress states. In this paper, we further develop an engineering model for microcrack propagation consistent with critical plane concepts for correlation of both LCF and high cycle fatigue (HCF) behavior, including multiple regimes of small crack growth. The critical plane microcrack propagation approach of McDowell and Berard serves as a starting point to incorporate multiple regimes of crack nucleation, shear growth under the influence of microstructural barriers, and transition to linear crack length-dependent growth related to elastic-plastic fracture mechanics (EPFM) concepts. Microcrack iso-length data from uniaxial and torsional fatigue tests of 1045 steel and IN 718 are examined and correlated by introducing a transition crack length which governs the shift from nonlinear to linear crack length dependence of da/dN. This transition is related to the shift from strong microstructural influence to weak influence on the propagation of microcracks. Simple forms are introduced for both the transition crack length and the crack length-dependence of crack growth rate within the microcrack propagation framework (introduced previously by McDowell and Berard) and are employed to fit the 1045 steel and IN 718 microcrack iso-length data, assuming preexisting sub-grain size cracks. The nonlinear evolution of crack length with normalized cycles is then predicted over a range of stress amplitudes in uniaxial and torsional fatigue. The microcrack growth law is shown to have potential to correlate microcrack propagation behavior as well as damage accumulation for HCF-LCF loading sequences and sequences of applied stress states.     

Strain Accumulation in Ti-6Al-4V during Fatigue at High Mean Stress

The effect of mean stress and frequency on the high cycle fatigue behavior of Ti-6Al-4V has been investigated. It has been shown that a transition in the fatigue behavior occurs at a stress ratio of approximately 0.7. Above this value, the material exhibits measurable strain accumulation and necking. Since Ti-6Al-4V is susceptible to room temperature creep, an empirical model was developed using static creep data in an attempt to predict the cyclic behavior of the material. The model was unable to account for the large amounts of strain seen experimentally. In addition, closer examination of the data revealed that the deformation was more closely related to the number of cycles than to time.     

Smooth pursuit in schizophrenia: abnormalities of open- and closed-loop responses

This study, funded by the National Breast Screening Programme, was undertaken in 1992 at the Helen Garrod Breast Screening Unit, Nottingham. In a sample of 400 women who attended first round screening in 1989 and remained eligible for screening 10 per cent failed to attend triennial recall. A sample of a further 400 women who had been screened previously containing 200 women who re-attended for second round screening and 200 who failed to re-attend were studied anonymously by questionnaire. No significant difference existed between re-attenders and non-re-attenders in their perceived personal risk of breast cancer. A significant difference existed between the two groups in (1) their knowledge of breast cancer, (2) their ease of attending for screening, and (3) their previous experience of breast screening. Half of the women who failed to return implicated their initial visit in this decision--41 per cent implicating pain, 6 per cent stress and 3 per cent embarrassment. Hence a small percentage (5 per cent) of women do not re-attend for screening because of a negative experience at their initial visit. Every effort should therefore be made to make screening as acceptable as possible.     

An instrument for measuring the gas concentrations in geothermal wells

An instrument and technique for rapid measurement and monitoring of gas concentrations in steam discharged from geothermal wells is described. The instrument directly measures the partial pressure of non-condensible gases present in a sample of the total discharge, at a given temperature and a given total pressure. This is achieved by deducting the vapour pressure of distilled water, at the same temperature. from the combined pressure of the water vapour and gases present. The volume of gas in the discharge can be obtained from the differential pressure by application of the ideal gas law with appropriate data from the steam tables. The percentage by weight of gas in the fluids can also be obtained if the chemical composition of the gases present is known. The results compare favourably with other methods.     

Book reviews

Women, Housing and Community. W. Van Vliet, (ed). Avebury: Aldershot. 1988. pp204. £30.00, cloth.

Accommodating Inequality: Gender and Housing. S. Watson, Allen and Unwin: London. pp157. £9.95 paper, £25.00 cloth.

Social Housing and the Social Services. by Paul Spicker. Harlow: Longman and the Institute of Housing, 1989. 143pp. £11.95 (paper).     

Short communication: A study of Lactobacillus isolates' adherence to and influence on membrane integrity of human Caco-2 cells

The selection criteria of ideal probiotic bacteria are complex and involve many factors. One key criterion is based on the ability of the probiotic bacteria to adhere to the epithelial lining of the gastrointestinal tract. The objective of this study was to evaluate and compare the adherence and influence on membrane integrity of 2 selected lactobacilli isolates—Lactobacillus rhamnosus MI13 (dairy food origin) and L. plantarum RC2 (bovine rumen origin)—to Caco-2 cells in the presence and absence of Escherichia coli. The adhesion and influence on membrane integrity properties of the 2 Lactobacillus isolates were compared with Escherichia coli, a human commensal bacterium. From the adhesion studies, we concluded that the bovine rumen isolate exhibited better adherence to Caco-2 cells than the dairy food isolate. In contrast, the dairy food isolate better protected the Caco-2 monolayer from damage induced by ethanol.