High matrix metalloproteinase 1 (MMP1) expression is associated with enhanced breast cancer growth and metastasis and also might predict poor prognosis. In this study, we further investigated the functional role of MMP1 and how it is upregulated in multi-drug resistant (MDR) breast cancer cells. By retrieving microarray data in GEO datasets and the survival data in the Kaplan Meier plotter, we observed that MMP1 is significantly upregulated in MCF-7/ADR cells compared to the parental MCF-7 cells, while high MMP1 expression is associated with worse overall survival (OS) and recurrence free survival (RFS) in breast cancer patients after systematic therapy. Functional studies showed that MMP1 overexpression significantly reduced the drug sensitivity in MCF-7 cells, while MMP1 knockdown substantially enhanced the sensitivity in MCF-7/ADR cells. By performing western blotting and immunofluorescent staining, we confirmed that MCF-7/ADR cells had enhanced mesenchymal properties than MCF-7 cells. In MCF-7 cells, enforced Slug expression resulted in significant MMP1 upregulation, while in MCF-7/ADR cells, Slug knockdown led to reduced MMP1 expression. By performing bioinformatic analysis, we observed that the promoter of MMP1 has three putative Slug binding sites. The following dual luciferase assay and ChIP-qPCR verified these three binding sites. Therefore, we infer that Slug enhances MMP1 transcription via directly binding to the promoter region in breast cancer cells, which is a previously unrecognized mechanism in the development of MDR.

2014) Designing dynamic English: a creative reading system in a context-aware fitness centre using a smart phone and QR codes, Digital Creativity, 25:2, 169-186, AbstractThis article describes the design and development of a context-aware ubiquitous learning (u-learning) system for users to increase fitness-related reading comprehension in a fitness centre. With the use of mobile devices and sensing technologies, practitioners and researchers of ICT and ubiquitous computing (ubicomp) are paying attention to the planning and use of u-learning components to provide users more interactions with authentic learning objects in a real context. Meanwhile, English for specific purposes (ESP) with interaction design has been a focus in recent years; however, few ESP practitioners and researchers have explored fitness-related English with ubicomp. All of the users were satisfied with the use of the smart phones and scanning of QR codes on the machines in the fitness centre to develop their reading comprehension of fitness-related English. Finally, a learning design model for Fitness English reading with u-learning components was developed and elaborated from designers' perspectives.

During positive pressure mechanical ventilation, percentile systolic pressure variation (%SPV) or respiratory-related arterial pressure variability (RAPV) have both been used in assessment of graded haemorrhage. We aimed to investigate whether changes in %SPV and RAPV are correlated during graded haemorrhage (by 5, 10 or 20% of the estimated blood volume) in anaesthetized positive pressure ventilated rats and to investigate the involvement of autonomic regulation. Saline vehicle or atropine produced no discernible effect on baseline %SPV or RAPV but, thereafter, %SPV and RAPV increased progressively with graded haemorrhage. Propranolol significantly decreased baseline %SPV and RAPV and changes induced in %SPV and RAPV by graded haemorrhage. Phentolamine significantly enhanced baseline %SPV and RAPV, and further enhancement of %SPV and RAPV by graded haemorrhage did not occur until 20% of the estimated blood volume was removed. RAPV was significantly correlated with %SPV in all experimental groups. We conclude that RAPV is comparable with%SPV as an indicator of graded haemorrhage and that, in anaesthetized and positive pressure ventilated rats, both are dependent on autonomic function, especially beta-adrenoceptors.

Constant-force mechanisms (CFMs) can produce an almost invariant output force over a limited range of input displacement. Without using additional sensor and force controller, adjustable CFMs can passively produce an adjustable constant output force to interact with the working environment. In the literature, one-dimensional CFMs have been developed for various applications. This paper presents the design of a novel CFM that can produce adjustable constant force in two dimensions. Because an adjustable constant force can be produced in each radial direction, the proposed adjustable CFM can be used in applications that require two-dimensional force regulation. In this paper, the design formulation and simulation results are presented and discussed. Equations to minimize the output force variation are given to choose the design parameters optimally. A prototype of the two-dimensional CFM is tested to demonstrate the effectiveness and accuracy of adjustable force regulation. This novel CFM is expected to be used in machines or robots to interact friendly with the environment.