Variable drug responses among malignant cells within individual tumors may represent a barrier to their eradication using chemotherapy. Carcinoma cells expressing mesenchymal markers resist conventional and epidermal growth factor receptor (EGFR)-targeted chemotherapy. Here we evaluated whether mesenchymal-like subpopulations within human squamous cell carcinomas (SCCs) with predominantly epithelial features contribute to overall therapy resistance. We identified a mesenchymal-like subset expressing low E-cadherin (Ecad-lo) and high vimentin (Vim-hi) within upper aerodigestive tract SCCs. This subset was both isolated from cell lines and identified in xenografts and primary clinical specimens. The Ecad-lo subset contained more low-turnover cells, correlating with resistance to the conventional chemotherapeutic paclitaxel in vitro. Epidermal growth factor (EGF) induced less stimulation of the MAP kinase and PI3-kinase pathways in Ecad-lo cells, which was likely due to lower EGFR expression in this subset and correlated with in vivo resistance to the EGFR-targeted antibody cetuximab. The Ecad-lo and high E-cadherin (Ecad-hi) subsets were dynamic in phenotype, showing the capacity to repopulate each other from single cell clones. Taken together, these results provide evidence for a low-turnover, mesenchymal-like subpopulation in SCCs with diminished EGFR pathway function and intrinsic resistance to conventional and EGFR-targeted chemotherapies.

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The current paper deals with the dexterity and stiffness of a three-degree of freedom (DOF) planar parallel manipulator with actuation redundancy, which is a subpart of a four-DOF-hybrid machine tool. Based on the kinematics, the dexterity is analysed. The stiffness indices, which are the maximum deflection of the moving platform under the action of a unit force and the minimum eigenvalue of the stiffness matrix of the manipulator, are presented for investigating the stiffness. According to the minimum eigenvalue index, it is proved that actuation redundancy can improve the stiffness of the parallel manipulator. Moreover, the relationship between the singular configuration and the stiffness of the parallel manipulator is discussed. Compared with the corresponding non-redundant parallel manipulator without the redundant link, the redundantly actuated parallel manipulator has better dexterity and higher stiffness.

ABSTRACT. Prolactin receptor (PRLR) is the specific receptor for prolactin. Brain-specific control of PRLR gene expression is correlated with the induction of maternal behavior. The aim of this study was to investigate the dynamic changes in the PRLR mRNA level in the sheep pituitary gland and its effect on ewe maternal behavior. The mRNA expression of PRLR during non-pregnancy stage was maintained at low but detectable levels, as was the case during mid-gestation. After that, expression began increasing and reached a maximum during the early postpartum followed by a gradual decline during the mid-postpartum and late postpartum stages. A trend of higher PRLR mRNA expression was observed during the postpartum stage relative to the non-pregnancy and pregnancy stages. Expression of PRLR mRNA was significantly higher in the normal maternal behavior group than that in the abnormal maternal behavior group. There may be a correlation between PRLR mRNA expression and ewe maternal behavior, especially in early postpartum.