In this study, thermally responsive polymeric nanoparticle-encapsulated curcumin (nCCM) was prepared and characterized. The nCCM is ~22 and 300 nm in diameter at 37 and 22 °C, respectively. The smaller size of the nCCM at 37 °C was found to significantly facilitate its uptake in vitro by human prostate adenocarcinoma PC-3 cancer cells. However, the intracellular nCCM decreases rapidly (rather than plateaus) after reaching its peak at ~1.5 h during a 3-day incubation of the PC-3 cells with nCCM. Moreover, a mild hyperthermia (with negligible cytotoxicity alone) at 43 °C applied between 1 and 1.5 h during the 3-day incubation not only increases the peak uptake but also alters intracellular distribution of nCCM (facilitating its delivery into cell nuclei), which helps to retain a significantly much higher level of intracellular curcumin. These effects of mild hyperthermia could be due in part to the thermal responsiveness of the nCCM: they are more positively charged at 43 °C and can be more easily attracted to the negatively charged nuclear membrane to enter nuclei as a result of electrostatic interaction. Ultimately, a combination of the thermally responsive nCCM and mild hyperthermia significantly enhances the anticancer capability of nCCM, resulting in a more than 7-fold decrease in its inhibitory concentration to reduce cell viability to 50% (IC50). Further mechanistic studies suggest injury pathways associated with heat shock proteins 27 and 70 should contribute to the enhanced cancer cell destruction by inducing cell apoptosis and necrosis. Overall, this study demonstrates the potential of combining mild hyperthermia and thermally responsive nanodrugs such as nCCM for augmented cancer therapy.
Model validation using data from modal tests is now widely practiced in many industries for advanced structural dynamic design analysis, especially where structural integrity is a primary requirement. These industries tend to demand highly efficient designs for their critical structures which, as a result, are increasingly operating in regimes where traditional linearity assumptions are no longer adequate. In particular, many modern structures are found to contain localized areas, often around joints or boundaries, where the actual mechanical behaviour is far from linear. Such structures need to have appropriate representation of these nonlinear features incorporated into the otherwise largely linear models that are used for design and operation. This paper proposes an approach to this task which is an extension of existing linear techniques, especially in the testing phase, involving only just as much nonlinear analysis as is necessary to construct a model which is good enough, or ‘valid’: i.e. capable of predicting the nonlinear response behaviour of the structure under all in-service operating and test conditions with a prescribed accuracy. A short-list of methods described in the recent literature categorized using our framework is given, which identifies those areas in which further development is most urgently required.
The presentation will show that thermographic NDT, which has long been associated with the detection of sub-surface in-plane faults in composites or coatings, also has great potential to compete with DPI and MPI for the detection of cracks in metallic components. Work on three thermographic NDE techniques that have been developed to locate and image cracks in metallic components will be reviewed. These techniques are: thermosonics (sonic IR, ultrasonically stimulated thermography); laser spot thermographic imaging and pulsed eddy current stimulated (induction) thermography. The three techniques will be explained and examples will be given of their performance in imaging well characterised cracks. Factors concerning the practical and reliable implementation of the techniques will be discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.