Endocytosis of the ASGP receptor H1 is reduced by mutation of tyrosine-5 but still occurs via coated pits

The clustering of plasma membrane receptors in clathrin-coated pits depends on determinants within their cytoplasmic domains. In several cases, individual tyrosine residues were shown to be necessary for rapid internalization. We have mutated the single tyrosine at position 5 in the cytoplasmic domain of the major subunit H1 of the asialoglycoprotein receptor to alanine. Expressed in fibroblasts cells, the mutant protein was accumulated in the plasma membrane, and its rate of internalization was reduced by a factor of four. The residual rate of endocytosis, however, was still significantly higher than that of resident plasma membrane proteins. Upon acidification of the cytoplasm, which specifically inhibits the formation of clathrin-coated vesicles but not uptake of the fluid phase marker Lucifer yellow, residual endocytosis was blocked. By immunoelectron microscopy mutant H1 could be directly demonstrated in coated pits. The fraction of wild-type and mutant H1 present in coated pits as determined by immunogold localization correlated well with the respective rates of internalization. Thus, mutation of tyrosine-5 only partially inactivates recognition of H1 for incorporation into coated pits

European Mothers' Time with Children: Differences and Similarities across Nine Countries

We use data from the 1996 wave of the European Community Household Panel to present and compare the weekly number of hours mothers of children less than 16 years of age reported looking after children in nine European countries in 1996. In addition, we explore to what extent cross-country differences in socio-demographic characteristics and parents' employment status contribute to differences in maternal time with children across the nine countries. We find cross-country differences in the mean of the amount of time mothers reported looking after children. Only a small portion of these differences is explained by differences in socio-demographic characteristics and employment status across countries in Europe. For three country pairs, we use a Oaxaca decomposition to investigate whether behaviour differences or differences in sample characteristics explain more of the observed differences in mothers' time looking after children. According to our results, the differences between Ireland and the UK can be explained mainly by behaviour differences. The results for Germany vs. Austria and Denmark vs. Greece, however, depend on the weights used.

The reverse protraction factor in the induction of bone sarcomas in radium-224 patients

More than 50 bone sarcomas have occurred among a collective of about 800 patients who had been injected in Germany after World War II with large activities of radium-224 for the intended treatment of bone tuberculosis and ankylosing spondylitis.^In an earlier analysis it was concluded that, at equal mean absorbed doses in the skeleton, patients with longer exposure time had a higher incidence of bone sarcomas.^The previous analysis was based on approximations; in particular, it did not account for the varying times at risk of the individual patients.^In view of the implications of a reverse protraction factor for basic considerations in radiation protection, the need was therefore felt to reevaluate the data from the continued follow-up by more rigorous statistical methods.^A first step of the analysis demonstrates the existence of the reverse dose-rate effect in terms of a suitably constructed rank-order test.^In a second step of the analysis it is concluded that the data are consistent with a linear no-threshold dose dependence under the condition of constant exposure time, while there is a steeper than linear dependence on dose when the exposure times increase proportionally to dose.^A maximum likelihood fit of the data is then performed in terms of a proportional hazards model that includes the individual parameters, dose, treatment duration, and age at treatment.^The fit indicates proportionality of the tumor rates to mean skeletal dose with an added factor (1 + 0.18.tau), where tau is the treatment time in months.^This indicates that a protraction of the injections over 15 months instead of 5 months doubles the risk of bone sarcoma

The use of lasers in veterinary ophthalmology: Recommendations based on literature: Laseranwendungen in der Veterinär-Ophthalmologie: Empfehlungen auf Basis der Literatur

Lasers are routinely used in veterinary ophthalmology for the treatment of a number of ophthalmic conditions and diseases. In veterinary ophthalmology, gas lasers (CO2 lasers) and semiconductor lasers (diode lasers) are used primarily, but the therapy of posterior capsular opacification with the Nd:YAG laser has also been described. This paper presents and discusses the most common indications for the use of the diode and CO2 lasers. Diode lasers are mainly used in the treatment of glaucoma, either by transscleral cyclophotocoagulation or by endoscopic cyclophotocoagulation. Other indications are various forms of retinal detachments, as well as pigmented neoplasms of the uvea. An emerging field in veterinary ophthalmology using diode lasers is photodynamic therapy of periocular tumors. CO2 lasers are used for pars plana vitrectomies and surgical excision of ocular tumor

Estimation of multivariate probit models: A mixed generalized estimating/pseudo-score equations approach and some finite sample results

In the present paper a mixed approach is proposed for the simultaneously estimation of regression and correlation structure parameters in multivariate probit models using generalized estimating equations for the former and pseudo-score equations for the latter. The finite sample properties of the corresponding estimators are compared to estimators proposed by Qu, Williams, Beck and Medendorp (1992) and Qu, Piedmonte and Williams (1994) using generalized estimating equations for both sets of parameters via a Monte Carlo experiment. As a `reference' estimator for an equicorrelation model, the maximum likelihood (ML) estimator of the random effects probit model is calculated. The results show the mixed approach to be the most robust approach in the sense that the number of datasets for which the corresponding estimates converged was largest relative to the other two approaches. Furthermore, the mixed approach led to the most efficient non-ML estimators and to very efficient estimators for regression and correlation structure parameters relative to the ML estimator if individual covariance matrices were used

A mixed approach and a distribution free multiple imputation technique for the estimation of multivariate probit models with missing values

In the present paper a mixed generalized estimating/pseudo­score equations (GEPSE) approach together with a distribution free multiple imputation technique is proposed for the estimation of regression and correlation structure parameters of multivariate probit models with missing values for an ordered categorical time invariant variable. Furthermore, a generalization of the squared trace correlation (R_T^2) for multivariate probit models, denoted as pseudo R_T^2, is proposed. A simulation study was conducted, simulating a probit model with an equicorrelation structure in the errors of an underlying regression model and using two different missing mechanisms. For a low `true' correlation the difference between the GEPSE, a generalized estimating equations (GEE) and a maximum likelihood (ML) estimator were negligible. For a high `true' correlation the GEPSE estimator turned out to be more efficient than the GEE and very efficient relative to the ML estimator. Furthermore, the pseudo R_T^2 was close to R_T^2 of the underlying linear model. The mixed approach is illustrated using a psychiatric data set of depressive inpatients. The results of this analysis suggest, that the depression score at discharge from a psychiatric hospital and the occurence of stressful life events seem to increase the probability of having an episode of major depression within a one­year interval after discharge. Furthermore, the correlation structure points to short­time effects on having or not having a depressive episode, not accounted for in the systematic part of the regression model