Aqueous in-flow synthesis of T1 enhancing iron oxide nanoparticles for breast cancer theranostics

Superparamagnetic iron oxide nanoparticles (SPIONs) have gained signif- icant interest over the past decades because of their wide range of appli- cations. In biomedicine, SPIONs had been used extensively in the past as MRI contrast agents but they are currently being investigated for hyperther- mia therapies, magnetic manipulation and as part of diagnostic devices. The main aim of this study is to develop a method to synthesise positive MRI enhancing iron oxide nanoparticles (T1) and use these as the diagnos- tic component to produce a theranostic (therapeutic and diagnostic) agent. An aqueous flow-based synthesis method was assembled and tested producing 25nm iron oxide nanoparticles with T1 enhancement, CMDxUS- PIONs. The devised synthetic method enabled the fabrication of the desired nanoparticles without the use of organic solvents and at higher outputs than previously reported with flow-based methods, with 12 clinical doses being produced per hour using a lab-scale system. Surface functionalisation of CMDxUSPIONs with aptamers for active targeting was accomplished using a recently discovered anti-annexin 2A aptamer (ACE4). Particle uptake results show that ACE4-CMDxUSPIONs presented at least a two-fold increase in cell uptake when compared to un- modified CMDxUSPIONs. Further modifications of CMDxUSPIONs included drug-loading with cisplatin. Cisplatin loaded CMDxUSPIONs (CPt-CMDxUSPIONs) were achieved following pre-optimisation using a Design of Experiments ap- proach. The drug-loaded CPt-CMDxUSPIONs containing 0.64mg of CPt/mg of iron were able to retain both the activity of free cisplatin (in vitro) and the imaging capabilities of CMDxUSPIONs. In vivo experiments using a 4T1 mammary carcinoma cell line in Balb/C mice showed that CPt-CMDxUSPIONs were trackable in a 1T preclinical MRI and therapeutically, CPt-CMDxUSPIONs reduced tumour size and minimised cisplatin’s nephro- toxicity. Moreover, preclinical MRI scans show that it is possible to use CMDxUSPIONs as reporters for nanoparticle uptake detected by a T1-T2 signal switch in MRI. Iron oxide based theranostic systems reported in this thesis could play an important role in future cancer treatments by enabling a personalised therapy approach and modifying current chemotherapeutic drug biodistribu- tion as a carrier. The facile synthesis together with the addition of therapeu- tic agents to iron oxide nanoparticles demonstrates that the production of an experimental theranostic is possible

What Users Trust in Paying-for-knowledge: An Empirical Study of Chinese Online Q&A Community

In the era of information explosion, desire for high-quality information has triggered the development of paying-for-knowledge. Even paying-for-knowledge has interesting business model, there are several problems to be solved, and one of the most salient problem is what influences users’ payment behaviors. Previous researches indicate that trust is one of the most important factors in paying-for-knowledge. However, the specific influence mechanism of trust remains unknown. In this paper, we tried to estimate the effects of character trust and situational trust. For validating our hypotheses, text analysis and economics are combined in this research. The authors find that competence-based trust, benevolence-based trust and situational trust all have positive effects on consumers\u27 behavior of paying-for-knowledge. The findings are expected to help the sustainable development of paying-for-knowledge

Negotiating the female successor-leader role within family business succession in China

This article explores the approaches of identity construction used by Chinese daughters while negotiating the successor–leader role within family businesses. A qualitative interpretivist approach was adopted to understand daughter views on gender, family business leadership and succession, as well as the approaches adopted to negotiate the role of female successor/leader in the Chinese family business. Twenty semi-structured interviews were conducted with both actual and potential female successors. Three approaches of identity construction emerged based on the degree of conformity to traditional gender roles and Confucian family values: first, to abide by conventional gender expectations and perceive themselves as a temporary leader; second, to act as the ‘second leader’ and remain involved in decision making and third, to challenge conventional gender roles and strive to be an independent leader. This article contributes to debates on women in family business and gendered identity construction of daughters in family business in the Chinese context

Adaptive grid generation based onthe least-squares finite-element method

AbstractApproximate solutions of a partial differential equation become inaccurate if they arecomputed on a fixed grid that is not sufficiently fine in regions of the domain where the variables change rapidly. For time dependent problems, special features of a partial differential equation and their location could change in time as well. Thus, adaptive grid methods are necessary.In this paper, we develop an adaptive deformation method based on the least-squares finite-element method (LSFEM). A main advantage of this method as compared to the existing deformation method is its ability to generate adaptive grids on domains with moving boundary. It computes the node velocity from a div-curl system according to an error indicator (monitor function), and then moves the nodes to new locations so that the size of the new grid cells can be directly controlled. In this method, the connectivity of the nodes is unchanged if the grid quality is acceptable. Otherwise, various optimization procedures can be applied after node movements to improve grid quality. The grid formed becomes refined in regions where the solution error is large

Development of a trench cutting re-mixing deep wall method model test device

The trench cutting re-mixing deep wall (TRD) is a new type of underground waterproof curtain. Mixing uniformity is the key index affecting the efficiency and quality of this method. However, because of many influencing factors, existing theories cannot be used to express the relationship between various factors and mixing uniformity. By analyzing the cutting and mixing process of the TRD method, the main factors affecting the uniformity of the mixing were obtained. A model test device was designed and manufactured, based on Buckingham's pi theorem. The validity of the model test device was verified through a comparative analysis of model and field test results. The model test device was demonstrated to be able to simulate the mixing process of the TRD method. The results provide guidance for promotion and better application of the TRD method